Materiały źródłowe

• #1 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. […] Currently, there is no effective treatment for this disease. Clinical cases of bone marrow or cord blood transplantation have been reported, however the therapeutic effectiveness of these methods remains insufficient to prevent aggravation of neurological disorders. […] Encouraging results have been obtained using gene therapy for delivering the wild-type ARSA gene using vectors based on various serotypes of adeno-associated viruses, as well as using mesenchymal stem cells and combined gene-cell therapy. This review discusses therapeutic strategies for the treatment of metachromatic leukodystrophy, as well as diagnostic methods and modeling of this pathology in animals to evaluate the effectiveness of new therapies.

• #2 MLD Foundation

  https://mld.foundation/

  Metachromatic Leukodystrophy (MLD) is a progressive, genetic, neurometabolic disease that affects the nervous system due to the lack of an enzyme, Ayrlsulfatase-A (ARSA.) […] While there is now an FDA-approved gene therapy available for pre-symptomatic infantile and early juveniles, Lenmeldy, access for early-symptomatic cases, older patient cases is much more limited or non-existent. […] For more information on therapies and their access requirements, visit MLD Therapies. […] Learn about the FDA-approved gene therapy for MLD, Lenmedly from Orchard Therapeutics, and other research that is underway. […] From diagnosis onward, we provide support, education, resources, and help advance research to eliminate and cure MLD.

• #3 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Metachromatic leukodystrophy can’t be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder. […] Metachromatic leukodystrophy can be managed with several treatment approaches: […] Medications may reduce signs and symptoms, such as behavioral problems, seizures, difficulty with sleeping, gastrointestinal issues, infection and pain. […] Physical therapy to promote muscle and joint flexibility and maintain range of motion may be helpful. Occupational and speech therapy can help maintain functioning. […] Working with a nutrition specialist (dietitian) can help provide proper nutrition. Eventually, it may become difficult to swallow food or liquid. This may require assistive feeding devices as the condition progresses.

• #4 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Symptomatic supportive care is indicated for problems including, but not limited to, behavioral disturbances, feeding difficulties, seizures, and constipation. No effective treatment is available to reverse the deterioration and loss of function that metachromatic leukodystrophy causes. […] Several treatment approaches are promising and include bone marrow or blood transplantation, gene therapy, enzyme replacement therapy, and cell therapy. […] Allogeneic blood or marrow transplantation is a standard of care for patients with certain inborn errors of metabolism. […] Early and late outcomes show promise for MLD pediatric patients after cord blood transplantation. […] Remyelination was observed after hematopoetic stem cell transplantation (HSCT), and importance of immunomodulation in addition to metabolic correction in MLD patients was highlighted for promotion of white matter recovery.

• #5 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Today, the U.S. Food and Drug Administration approved Lenmeldy (atidarsagene autotemcel), the first FDA-approved gene therapy indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD). […] This is the first FDA-approved treatment option for children who have this rare genetic disease, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research (CBER). […] Lenmeldy is a one-time, individualized single-dose infusion made from the patients own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. […] The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD.

• #6 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

  https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy-302091811.html

  Today, the U.S. Food and Drug Administration approved Lenmeldy (atidarsagene autotemcel), the first FDA-approved gene therapy indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD). […] There is no cure for MLD, and treatment typically focuses on supportive care and symptom management. […] Lenmeldy is a one-time, individualized single-dose infusion made from the patient’s own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. […] The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD.

• #7 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Today, the U.S. Food and Drug Administration approved Lenmeldy (atidarsagene autotemcel), the first FDA-approved gene therapy indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD). […] This is the first FDA-approved treatment option for children who have this rare genetic disease, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research (CBER). […] Lenmeldy is a one-time, individualized single-dose infusion made from the patients own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. […] The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD.

• #8 List of Metachromatic Leukodystrophy Medications

  https://www.drugs.com/condition/metachromatic-leukodystrophy.html

  Lenmeldy (atidarsagene autotemcel) is the first FDA-approved gene therapy for MLD. It is indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) – collectively referred to as early-onset MLD. […] Lenmeldy works to correct the underlying genetic cause of MLD by inserting one or more functional copies of the human ARSA gene into the genome of a patient’s own hematopoietic stem cells using a lentiviral vector. The genetically repaired stem cells are infused back into the patient, where they engraft (attach and multiply) within the bone marrow, supplying the body with myeloid cells that produce the ARSA enzyme. Restoring enzymatic function can potentially stop or slow the progression of MLD with a single treatment.

• #9 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  An appropriately matched and unaffected relative, in whom the cells manufacture adequate levels of arylsulfatase A, should serve as a donor. […] In addition to bone marrow transplantation, the development of gene therapy is a possible solution to correct the underlying genetic abnormality. […] Hematopoietic stem cell gene therapy shows evidence of safety and clinical benefit for late-infantile and older pediatric patients with MLD. […] The FDA approved atidarsagene autotemcel, a one-time, single-dose autologous hematopoietic stem cell-based gene therapy in 2024. […] It is indicated for treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). […] The one-time, single-dose IV infusion inserts 1 or more functional copies of human ARSA complementary deoxyribonucleic acid (cDNA) into the patients HSCs, through transduction of autologous CD34+ cells with ARSA lentiviral vector.

• #10 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Functional ARSA enzyme can break down or prevent the harmful accumulation of sulfatides. […] The FDA approval of atidarsagene autotemcel is based on data from 37 pediatric patients with early-onset MLD, enrolled in 2 single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. […] All treated patients were administered atidarsagene autotemcel and subsequently monitored at Ospedale San Raffaele in Milan, Italy. […] All children with PSLI MLD who were treated with atidarsagene autotemcel were alive at 6 years of age, compared with 58% of children in the natural history group. […] Additionally, children with PSEJ and ESEJ MLD showed slowing of motor and/or cognitive disease.

• #11 CALD and MLD

  https://patienteducation.asgct.org/disease-treatments/leukodystrophy

  LENMELDY is an FDA-approved gene therapy for infants and children with metachromatic leukodystrophy (MLD) who have not yet exhibited symptoms and children with early stage MLD. […] Gene therapy introduces a working version of the faulty gene into the cells in charge of creating key proteins. […] The modified cells then produce the protein that was missing or defective prior to treatment. […] This treatment aims to be one-time and to halt disease progression. […] Currently, HSC transplantation using donor (allogeneic) stem cells is the standard therapy for cerebral ALD and MLD. […] LENMELDY is an FDA approved one-time cell-based gene therapy utilizing a lentiviral vector for the treatment of individuals with late infantile or early juvenile forms of the disease who have not yet developed symptoms.

• #12

  https://mpssociety.org.uk/latest/treatment-for-metachromatic-leukodystrophy-mld-approved-by-the-european-commission

  With Libmeldy, a patients own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a self-inactivating (SIN) lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying disease with a single treatment. […] The EC approval of Libmeldy comes more than a decade after the first patient was treated in clinical trials performed at our Institute, and ushers in a remarkable and long-awaited shift in the treatment landscape for eligible MLD patients. […] As a community, we have been desperate for a treatment for young MLD patients, and we are incredibly excited to now have such a ground-breaking option approved in the EU.

• #13 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Functional ARSA enzyme can break down or prevent the harmful accumulation of sulfatides. […] The FDA approval of atidarsagene autotemcel is based on data from 37 pediatric patients with early-onset MLD, enrolled in 2 single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. […] All treated patients were administered atidarsagene autotemcel and subsequently monitored at Ospedale San Raffaele in Milan, Italy. […] All children with PSLI MLD who were treated with atidarsagene autotemcel were alive at 6 years of age, compared with 58% of children in the natural history group. […] Additionally, children with PSEJ and ESEJ MLD showed slowing of motor and/or cognitive disease.

• #14 FDA Approves First Gene Therapy for Children With Metachromatic Leukodystrophy

  https://www.aabb.org/news-resources/news/article/2024/03/19/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy

  The Food and Drug Administration on Monday approved the first and only gene therapy for the treatment of children with metachromatic leukodystrophy (MLD), a rare, debilitating, genetic disease that affects the brain and nervous system. […] Atidarsagene autotemcel (marketed as Lenmeldy, Orchard Therapeutics) is a one-time, individualized single-dose infusion made from autologous hematopoietic stem cells that have been genetically modified to include functional copies of the ARSA gene using a lentiviral vector. […] FDA based its approval on data from 37 children who received atidarsagene autotemcel in two single-arm clinical trials and an expanded access program. Results showed significant reductions in severe motor impairment or death compared to untreated children. […] Treatment also slowed disease progression in early juvenile MLD cases.

• #15 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression, said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to only 58% of children in the natural history group. […] At 5 years of age, 71% of treated children were able to walk without assistance. […] Eighty five percent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. […] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease.

• #16 FDA approves innovative gene therapy for MLD

  https://www.europeanpharmaceuticalreview.com/news/221137/fda-approves-innovative-gene-therapy-for-mld/

  FDA stated that the safety and effectiveness of Lenmeldy was assessed based on clinical data, including evidence which showed that Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] All the children who were given Lenmeldy were alive at six years of age, compared to only 58 percent of the children not treated with the gene therapy, according to the FDA. Furthermore, at five years of age, 71 percent of treated children were able to walk without assistance. […] The gene therapy, known as Libmeldy in Europe, has already been approved by the European Commission, UK Medicines and Healthcare products Regulatory Agency (MHRA), and Swiss Agency for Therapeutic Products (Swissmedic).

• #17 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression, said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to only 58% of children in the natural history group. […] At 5 years of age, 71% of treated children were able to walk without assistance. […] Eighty five percent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. […] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease.

• #18 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Functional ARSA enzyme can break down or prevent the harmful accumulation of sulfatides. […] The FDA approval of atidarsagene autotemcel is based on data from 37 pediatric patients with early-onset MLD, enrolled in 2 single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. […] All treated patients were administered atidarsagene autotemcel and subsequently monitored at Ospedale San Raffaele in Milan, Italy. […] All children with PSLI MLD who were treated with atidarsagene autotemcel were alive at 6 years of age, compared with 58% of children in the natural history group. […] Additionally, children with PSEJ and ESEJ MLD showed slowing of motor and/or cognitive disease.

• #19 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

  https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy-302091811.html

  „MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. […] There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy.

• #20 FDA Approves First Gene Therapy for Metachromatic Leukodystrophy | Today’s Clinical Lab

  https://www.clinicallab.com/fda-approves-first-gene-therapy-for-metachromatic-leukodystrophy-27814

  The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections, and hepatomegaly. […] There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy.

• #21 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

  https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy-302091811.html

  „MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. […] There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy.

• #22 FDA Approves First Gene Therapy for Children With Metachromatic Leukodystrophy

  https://www.aabb.org/news-resources/news/article/2024/03/19/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy

  FDA recommended monitoring patients for neutrophil counts, delayed platelet engraftment and potential risks such as blood clots and encephalitis. […] In addition, FDA advised lifelong monitoring of treated patients for hematologic malignancies, including annual complete blood counts and integration site analysis for at least 15 years post-treatment.

• #23 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

  https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy-302091811.html

  „MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. […] There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy.

• #24 FDA Approves First Gene Therapy for Children With Metachromatic Leukodystrophy

  https://www.aabb.org/news-resources/news/article/2024/03/19/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy

  FDA recommended monitoring patients for neutrophil counts, delayed platelet engraftment and potential risks such as blood clots and encephalitis. […] In addition, FDA advised lifelong monitoring of treated patients for hematologic malignancies, including annual complete blood counts and integration site analysis for at least 15 years post-treatment.

• #25 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Symptomatic supportive care is indicated for problems including, but not limited to, behavioral disturbances, feeding difficulties, seizures, and constipation. No effective treatment is available to reverse the deterioration and loss of function that metachromatic leukodystrophy causes. […] Several treatment approaches are promising and include bone marrow or blood transplantation, gene therapy, enzyme replacement therapy, and cell therapy. […] Allogeneic blood or marrow transplantation is a standard of care for patients with certain inborn errors of metabolism. […] Early and late outcomes show promise for MLD pediatric patients after cord blood transplantation. […] Remyelination was observed after hematopoetic stem cell transplantation (HSCT), and importance of immunomodulation in addition to metabolic correction in MLD patients was highlighted for promotion of white matter recovery.

• #26 CALD and MLD

  https://patienteducation.asgct.org/disease-treatments/leukodystrophy

  LENMELDY is an FDA-approved gene therapy for infants and children with metachromatic leukodystrophy (MLD) who have not yet exhibited symptoms and children with early stage MLD. […] Gene therapy introduces a working version of the faulty gene into the cells in charge of creating key proteins. […] The modified cells then produce the protein that was missing or defective prior to treatment. […] This treatment aims to be one-time and to halt disease progression. […] Currently, HSC transplantation using donor (allogeneic) stem cells is the standard therapy for cerebral ALD and MLD. […] LENMELDY is an FDA approved one-time cell-based gene therapy utilizing a lentiviral vector for the treatment of individuals with late infantile or early juvenile forms of the disease who have not yet developed symptoms.

• #27 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Symptomatic supportive care is indicated for problems including, but not limited to, behavioral disturbances, feeding difficulties, seizures, and constipation. No effective treatment is available to reverse the deterioration and loss of function that metachromatic leukodystrophy causes. […] Several treatment approaches are promising and include bone marrow or blood transplantation, gene therapy, enzyme replacement therapy, and cell therapy. […] Allogeneic blood or marrow transplantation is a standard of care for patients with certain inborn errors of metabolism. […] Early and late outcomes show promise for MLD pediatric patients after cord blood transplantation. […] Remyelination was observed after hematopoetic stem cell transplantation (HSCT), and importance of immunomodulation in addition to metabolic correction in MLD patients was highlighted for promotion of white matter recovery.

• #28 Metachromatic Leukodystrophy (MLD) | UPMC Children’s Hospital

  https://www.chp.edu/our-services/rare-disease-therapy/conditions-we-treat/metachromatic-leukodystrophy

  Right now, there’s no cure for MLD. […] Doctors will closely follow the progression of the disease and work to offer supportive care. This is care that helps improve your child’s quality of life. […] Children with MLD may find PT helps them move better. It can also make muscles less painful and stiff. […] Speech therapy can help children learn ways to communicate and treat swallowing issues. […] Your child’s doctor may also prescribe drugs to help: Prevent seizures. Manage pain. Get better sleep. Treat digestive issues. […] An umbilical cord blood transplant has extended the lives of many children with MLD. It can’t undo the damage done, but it may keep it from getting worse. […] Options for treating your child’s MLD. […] We’ll discuss the details if we think a transplant might be a good option for your child.

• #29 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  Symptomatic supportive care is indicated for problems including, but not limited to, behavioral disturbances, feeding difficulties, seizures, and constipation. No effective treatment is available to reverse the deterioration and loss of function that metachromatic leukodystrophy causes. […] Several treatment approaches are promising and include bone marrow or blood transplantation, gene therapy, enzyme replacement therapy, and cell therapy. […] Allogeneic blood or marrow transplantation is a standard of care for patients with certain inborn errors of metabolism. […] Early and late outcomes show promise for MLD pediatric patients after cord blood transplantation. […] Remyelination was observed after hematopoetic stem cell transplantation (HSCT), and importance of immunomodulation in addition to metabolic correction in MLD patients was highlighted for promotion of white matter recovery.

• #30 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  In individuals with asymptomatic late infantile and early juvenile forms of the disease, bone marrow or cord blood transplantation may stabilize neurocognitive function; however, symptoms of motor function loss frequently progress. […] Mildly symptomatic and asymptomatic late juvenile and adult-onset forms are more likely to be stabilized with bone marrow or blood transplantation because of slower disease progression. […] Patients should be carefully evaluated and counseled prior to bone marrow transplantation. […] The migration of hematopoietically derived cells in sufficient numbers to treat the affected areas usually requires 6 months to 1 year. […] Although transplantation may be successful, enzyme release to surrounding tissues can widely vary, often with unpredictable benefits.

• #31 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  The main difficulty in the treatment of diseases affecting the nervous system arises from the poor permeability of the BBB (blood-brain barrier), which restricts access of therapeutic compounds during systemic administration and results in low effectiveness of many therapeutic approaches. […] For pre-symptomatic patients, bone marrow transplantation (BMT) or hematopoietic stem cell (HSC) transplantation may be helpful, but the therapeutic potential of this procedure remains controversial. […] One of the first and most effective approaches to currently treat MLD is BMT and HSC transplantation (HSCT). […] However, cohort studies have showed that in patients with juvenile MLD, demyelination continues to progress after BMT in 31% of cases. […] In the case of HSCT, it has been reported that siblings with the juvenile form receiving transplantation after the onset of the first symptoms demonstrate significant decrease in psychomotor functions compared to before the onset of the disease.

• #32 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  In individuals with asymptomatic late infantile and early juvenile forms of the disease, bone marrow or cord blood transplantation may stabilize neurocognitive function; however, symptoms of motor function loss frequently progress. […] Mildly symptomatic and asymptomatic late juvenile and adult-onset forms are more likely to be stabilized with bone marrow or blood transplantation because of slower disease progression. […] Patients should be carefully evaluated and counseled prior to bone marrow transplantation. […] The migration of hematopoietically derived cells in sufficient numbers to treat the affected areas usually requires 6 months to 1 year. […] Although transplantation may be successful, enzyme release to surrounding tissues can widely vary, often with unpredictable benefits.

• #33 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  The main difficulty in the treatment of diseases affecting the nervous system arises from the poor permeability of the BBB (blood-brain barrier), which restricts access of therapeutic compounds during systemic administration and results in low effectiveness of many therapeutic approaches. […] For pre-symptomatic patients, bone marrow transplantation (BMT) or hematopoietic stem cell (HSC) transplantation may be helpful, but the therapeutic potential of this procedure remains controversial. […] One of the first and most effective approaches to currently treat MLD is BMT and HSC transplantation (HSCT). […] However, cohort studies have showed that in patients with juvenile MLD, demyelination continues to progress after BMT in 31% of cases. […] In the case of HSCT, it has been reported that siblings with the juvenile form receiving transplantation after the onset of the first symptoms demonstrate significant decrease in psychomotor functions compared to before the onset of the disease.

• #34 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A study has shown that in children with juvenile metachromatic leukodystrophy, if disease progression does happen after hematopoetic stem cell transplantation (HSCT), it happens early after HSCT and proceeds faster than in children that did not go through the transplantation. […] The bone marrow transplantation procedure can potentially carry significant morbidity and mortality rates. […] Therefore, patient counseling regarding the risks versus the potential for later stabilization of the disease is necessary. […] Evaluation for transplantation includes careful neuropsychological and developmental testing to establish current levels of function and to provide findings for comparison with future results. […] If patients are asymptomatic or mildly symptomatic, the evaluations mentioned above should be performed and multidisciplinary treatment needs to be discussed.

• #35 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A study has shown that in children with juvenile metachromatic leukodystrophy, if disease progression does happen after hematopoetic stem cell transplantation (HSCT), it happens early after HSCT and proceeds faster than in children that did not go through the transplantation. […] The bone marrow transplantation procedure can potentially carry significant morbidity and mortality rates. […] Therefore, patient counseling regarding the risks versus the potential for later stabilization of the disease is necessary. […] Evaluation for transplantation includes careful neuropsychological and developmental testing to establish current levels of function and to provide findings for comparison with future results. […] If patients are asymptomatic or mildly symptomatic, the evaluations mentioned above should be performed and multidisciplinary treatment needs to be discussed.

• #36 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  In individuals with asymptomatic late infantile and early juvenile forms of the disease, bone marrow or cord blood transplantation may stabilize neurocognitive function; however, symptoms of motor function loss frequently progress. […] Mildly symptomatic and asymptomatic late juvenile and adult-onset forms are more likely to be stabilized with bone marrow or blood transplantation because of slower disease progression. […] Patients should be carefully evaluated and counseled prior to bone marrow transplantation. […] The migration of hematopoietically derived cells in sufficient numbers to treat the affected areas usually requires 6 months to 1 year. […] Although transplantation may be successful, enzyme release to surrounding tissues can widely vary, often with unpredictable benefits.

• #37 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A therapeutic strategy that has been useful for patients with other metabolic storage diseases is direct enzyme replacement. […] In the United States and Europe, clinical trials are being carried out to evaluate the safety and efficacy of a recombinant human ARSA (rhARSA) enzyme, Metazym (Shire HGT). […] The phase I clinical trial for its use in children with late-infantile metachromatic leukodystrophy showed that the drug was safe. […] Results of the safety evaluation of intrathecal rhARSA administration showed that it was generally well tolerated by patients, and preliminary data suggest promise in further development of rhARSA therapy for patients with MLD. […] Another therapeutic approach under study in mice is the use of oligodendroglial cell therapy.

• #38 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A therapeutic strategy that has been useful for patients with other metabolic storage diseases is direct enzyme replacement. […] In the United States and Europe, clinical trials are being carried out to evaluate the safety and efficacy of a recombinant human ARSA (rhARSA) enzyme, Metazym (Shire HGT). […] The phase I clinical trial for its use in children with late-infantile metachromatic leukodystrophy showed that the drug was safe. […] Results of the safety evaluation of intrathecal rhARSA administration showed that it was generally well tolerated by patients, and preliminary data suggest promise in further development of rhARSA therapy for patients with MLD. […] Another therapeutic approach under study in mice is the use of oligodendroglial cell therapy.

• #39 Treatment for MLD | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/treatment/

  Currently, no effective treatment is available to reverse the deterioration and loss of function that Metachromatic Leukodystrophy (MLD) causes. […] Haematopoietic stem cell transplantation is available for sufferers of adult-onset MLD, but early intervention is essential to be beneficial. […] Unrelated umbilical cord blood transplants can be used for pre-symptomatic children who have been diagnosed with Juvenile MLD. […] A Clinical Trial for Gene Therapy for MLD is currently taking place in Milan, Italy. […] A new Clinical Trial has been announced by Shire (now part of Takeda Pharmaceutical Company Ltd) for Intrathecal Enzyme Replacement Therapy for children with Late-Infantile MLD. […] Other possible therapies that are being researched at the moment: Stem cells […] Substrate Reduction Therapy that is, not increasing production of the missing enzyme, but taking away the waste product produced i.e. the sulfatides which cause de-myelination.

• #40 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A therapeutic strategy that has been useful for patients with other metabolic storage diseases is direct enzyme replacement. […] In the United States and Europe, clinical trials are being carried out to evaluate the safety and efficacy of a recombinant human ARSA (rhARSA) enzyme, Metazym (Shire HGT). […] The phase I clinical trial for its use in children with late-infantile metachromatic leukodystrophy showed that the drug was safe. […] Results of the safety evaluation of intrathecal rhARSA administration showed that it was generally well tolerated by patients, and preliminary data suggest promise in further development of rhARSA therapy for patients with MLD. […] Another therapeutic approach under study in mice is the use of oligodendroglial cell therapy.

• #41 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  The main difficulty in the treatment of diseases affecting the nervous system arises from the poor permeability of the BBB (blood-brain barrier), which restricts access of therapeutic compounds during systemic administration and results in low effectiveness of many therapeutic approaches. […] For pre-symptomatic patients, bone marrow transplantation (BMT) or hematopoietic stem cell (HSC) transplantation may be helpful, but the therapeutic potential of this procedure remains controversial. […] One of the first and most effective approaches to currently treat MLD is BMT and HSC transplantation (HSCT). […] However, cohort studies have showed that in patients with juvenile MLD, demyelination continues to progress after BMT in 31% of cases. […] In the case of HSCT, it has been reported that siblings with the juvenile form receiving transplantation after the onset of the first symptoms demonstrate significant decrease in psychomotor functions compared to before the onset of the disease.

• #42 Metachromatic Leukodystrophy Treatment & Management: Medical Care, Consultations, Prevention

  https://emedicine.medscape.com/article/951840-treatment

  A therapeutic strategy that has been useful for patients with other metabolic storage diseases is direct enzyme replacement. […] In the United States and Europe, clinical trials are being carried out to evaluate the safety and efficacy of a recombinant human ARSA (rhARSA) enzyme, Metazym (Shire HGT). […] The phase I clinical trial for its use in children with late-infantile metachromatic leukodystrophy showed that the drug was safe. […] Results of the safety evaluation of intrathecal rhARSA administration showed that it was generally well tolerated by patients, and preliminary data suggest promise in further development of rhARSA therapy for patients with MLD. […] Another therapeutic approach under study in mice is the use of oligodendroglial cell therapy.

• #43 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Recently, the results of post-mortem brain tissue examination of two patients with MLD undergone HSCT and six patients without transplantation have been reported. […] Another approach similar to HSCT is cord blood cell transplantation (CBCT), since it is believed that cord blood cells more efficiently migrate to the CNS. […] Mesenchymal stem cells (MSCs) have also been tested in an attempt to find an effective treatment for MLD. […] A clinical case using MSCs in a 23-year-old woman with an adult form of MLD, which developed within 1 year with progressive neurological deterioration, has been described. […] Enzyme replacement therapy (ERT) was one of the first approaches used to increase the level of a normal enzyme, but it encountered a number of difficulties. […] The direct administration of viral vectors encoding the ARSA gene directly into the brain has been considered as a possible method of MLD therapy. […] Gene and combined gene-cell therapy are considered new promising methods for MLD therapy.

• #44 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Other treatments may be needed as the condition progresses. Examples include a wheelchair, walker or other assistive devices; mechanical ventilation to assist with breathing; treatments to prevent or address complications; and long-term care or hospitalization. […] Care for metachromatic leukodystrophy can be complex and change over time. Regular follow-up appointments with a team of medical professionals experienced in managing this disorder may help prevent certain complications and link you with appropriate support at home, school or work. […] Potential treatments for metachromatic leukodystrophy that are being studied include: […] Gene therapy and other types of cell therapy that introduce healthy genes to replace diseased ones […] Enzyme replacement or enhancement therapy to decrease buildup of fatty substances […] Substrate reduction therapy, which reduces the production of fatty substances.

• #45 Treatment for MLD | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/treatment/

  Currently, no effective treatment is available to reverse the deterioration and loss of function that Metachromatic Leukodystrophy (MLD) causes. […] Haematopoietic stem cell transplantation is available for sufferers of adult-onset MLD, but early intervention is essential to be beneficial. […] Unrelated umbilical cord blood transplants can be used for pre-symptomatic children who have been diagnosed with Juvenile MLD. […] A Clinical Trial for Gene Therapy for MLD is currently taking place in Milan, Italy. […] A new Clinical Trial has been announced by Shire (now part of Takeda Pharmaceutical Company Ltd) for Intrathecal Enzyme Replacement Therapy for children with Late-Infantile MLD. […] Other possible therapies that are being researched at the moment: Stem cells […] Substrate Reduction Therapy that is, not increasing production of the missing enzyme, but taking away the waste product produced i.e. the sulfatides which cause de-myelination.

• #46 MLD | Brains for Brain

  https://www.brains4brain.eu/developing-treatment-options-for-metachromatic-leukodystrophy-mld/

  Gene Therapy with HSCT to set up research studies and clinical trials using hematopoietic stem cell gene therapy to cross correct the ARSA deficiency by manipulation with therapeutic viral vectors and an autologous transplant. […] Substrate reduction therapy produced encouraging results since 60% of treated patients demonstrated residual activity.

• #47 Gene Therapy for Metachromatic Leukodystrophy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5027970/

  The early studies with AAV vectors utilized AAV2, a human derived AAV serotype that mediates persistent but low level expression with relatively slow onset. […] Our initial studies with AAV-mediated gene therapy for MLD were conducted with AAV5, and then with the discovery of the non-human primate derived serotypes, our second generation studies were carried out with AAVrh.10. […] In this study both AAV serotype vectors were administered to MLD mice at 2.3109 vg via an intraparenchymal route to the right striatum. The primary findings were: (1) AAVrh.10 transduced more neurons both at sites proximal to administration site and distal brain loci than AAV5; […] These results strongly supported the use of AAVrh. 10hARSA vector for CNS gene therapy in rapidly progressing early-onset forms of MLD. […] Armed with this rationale, a Phase I/II, open labeled, monocentric clinical trial (NCT01801709, ClinicalTrials.gov) has been instated in France to assess the safety and efficacy of AAVrh.10hARSA for treatment of early onset forms of MLD by gene therapy.

• #48 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Recently, the results of post-mortem brain tissue examination of two patients with MLD undergone HSCT and six patients without transplantation have been reported. […] Another approach similar to HSCT is cord blood cell transplantation (CBCT), since it is believed that cord blood cells more efficiently migrate to the CNS. […] Mesenchymal stem cells (MSCs) have also been tested in an attempt to find an effective treatment for MLD. […] A clinical case using MSCs in a 23-year-old woman with an adult form of MLD, which developed within 1 year with progressive neurological deterioration, has been described. […] Enzyme replacement therapy (ERT) was one of the first approaches used to increase the level of a normal enzyme, but it encountered a number of difficulties. […] The direct administration of viral vectors encoding the ARSA gene directly into the brain has been considered as a possible method of MLD therapy. […] Gene and combined gene-cell therapy are considered new promising methods for MLD therapy.

• #49 Gene Therapy for Metachromatic Leukodystrophy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5027970/

  The early studies with AAV vectors utilized AAV2, a human derived AAV serotype that mediates persistent but low level expression with relatively slow onset. […] Our initial studies with AAV-mediated gene therapy for MLD were conducted with AAV5, and then with the discovery of the non-human primate derived serotypes, our second generation studies were carried out with AAVrh.10. […] In this study both AAV serotype vectors were administered to MLD mice at 2.3109 vg via an intraparenchymal route to the right striatum. The primary findings were: (1) AAVrh.10 transduced more neurons both at sites proximal to administration site and distal brain loci than AAV5; […] These results strongly supported the use of AAVrh. 10hARSA vector for CNS gene therapy in rapidly progressing early-onset forms of MLD. […] Armed with this rationale, a Phase I/II, open labeled, monocentric clinical trial (NCT01801709, ClinicalTrials.gov) has been instated in France to assess the safety and efficacy of AAVrh.10hARSA for treatment of early onset forms of MLD by gene therapy.

• #50 Treatments – Therapies for metachromatic leukodystrophy

  https://www.mldinitiative.com/mld/treatments/

  Supportive care is an umbrella term that includes a wide range of treatments and services, of which a few are visualised above. […] Symptomatic treatment is an important aspect of disease management in MLD. Supportive care plays a big role in patients that are not suitable for causal therapy as well as patients who receive causal therapy. Some important elements of supportive care are summarised below. […] Treatment with an allogeneic hematopoietic stem cell transplantation (HSCT) provides a clinical and survival benefit for pre- and early-symptomatic patients with juvenile and adult MLD. Currently, this is the standard treatment in patients with MLD. […] Autologous HSCT-based gene therapy is a treatment that results in good functional outcomes for pre- and early-symptomatic patients with late-infantile MLD. […] Intrathecal administration of recombinant human ASA for symptomatic late-infantile patients is currently investigated in a clinical trial.

• #51 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Metachromatic leukodystrophy can’t be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder. […] Metachromatic leukodystrophy can be managed with several treatment approaches: […] Medications may reduce signs and symptoms, such as behavioral problems, seizures, difficulty with sleeping, gastrointestinal issues, infection and pain. […] Physical therapy to promote muscle and joint flexibility and maintain range of motion may be helpful. Occupational and speech therapy can help maintain functioning. […] Working with a nutrition specialist (dietitian) can help provide proper nutrition. Eventually, it may become difficult to swallow food or liquid. This may require assistive feeding devices as the condition progresses.

• #52 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is a genetic condition that causes a progressive decline in your mental and motor (movement) functions. Symptoms get worse over time. Treatment for the condition is mainly supportive and includes therapies like medication, occupational therapy and a feeding tube. […] Theres no cure for metachromatic leukodystrophy. The focus of treatment is to manage your symptoms and enhance your quality of life. In pre or minimally symptomatic children, healthcare providers may recommend stem cell transplants to slow the progression of the disease. […] Supportive treatment may include various medications for the following conditions: Seizures (anticonvulsant medications), Spasticity (muscle relaxants), Mood disorders (antidepressants), Pain (NSAIDs and other medications).

• #53 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is a genetic condition that causes a progressive decline in your mental and motor (movement) functions. Symptoms get worse over time. Treatment for the condition is mainly supportive and includes therapies like medication, occupational therapy and a feeding tube. […] Theres no cure for metachromatic leukodystrophy. The focus of treatment is to manage your symptoms and enhance your quality of life. In pre or minimally symptomatic children, healthcare providers may recommend stem cell transplants to slow the progression of the disease. […] Supportive treatment may include various medications for the following conditions: Seizures (anticonvulsant medications), Spasticity (muscle relaxants), Mood disorders (antidepressants), Pain (NSAIDs and other medications).

• #54 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Metachromatic leukodystrophy can’t be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder. […] Metachromatic leukodystrophy can be managed with several treatment approaches: […] Medications may reduce signs and symptoms, such as behavioral problems, seizures, difficulty with sleeping, gastrointestinal issues, infection and pain. […] Physical therapy to promote muscle and joint flexibility and maintain range of motion may be helpful. Occupational and speech therapy can help maintain functioning. […] Working with a nutrition specialist (dietitian) can help provide proper nutrition. Eventually, it may become difficult to swallow food or liquid. This may require assistive feeding devices as the condition progresses.

• #55 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Other types of therapy may include: Physical therapy to help with muscle strength and stiffness, Occupational therapy to improve your ability to perform daily tasks, Speech therapy to help with any speaking and swallowing issues, Psychotherapy to help with mental health conditions, Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition. […] You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved ones condition. […] Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably with the medical, social and emotional support necessary to cope with a serious health condition.

• #56 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Other types of therapy may include: Physical therapy to help with muscle strength and stiffness, Occupational therapy to improve your ability to perform daily tasks, Speech therapy to help with any speaking and swallowing issues, Psychotherapy to help with mental health conditions, Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition. […] You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved ones condition. […] Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably with the medical, social and emotional support necessary to cope with a serious health condition.

• #57 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Metachromatic leukodystrophy can’t be cured yet, but clinical trials hold some promise for future treatment. Current treatment is aimed at preventing nerve damage, slowing progression of the disorder, preventing complications and providing supportive care. Early recognition and intervention may improve outcomes for some people with the disorder. […] Metachromatic leukodystrophy can be managed with several treatment approaches: […] Medications may reduce signs and symptoms, such as behavioral problems, seizures, difficulty with sleeping, gastrointestinal issues, infection and pain. […] Physical therapy to promote muscle and joint flexibility and maintain range of motion may be helpful. Occupational and speech therapy can help maintain functioning. […] Working with a nutrition specialist (dietitian) can help provide proper nutrition. Eventually, it may become difficult to swallow food or liquid. This may require assistive feeding devices as the condition progresses.

• #58 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Other types of therapy may include: Physical therapy to help with muscle strength and stiffness, Occupational therapy to improve your ability to perform daily tasks, Speech therapy to help with any speaking and swallowing issues, Psychotherapy to help with mental health conditions, Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition. […] You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved ones condition. […] Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably with the medical, social and emotional support necessary to cope with a serious health condition.

• #59 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Other types of therapy may include: Physical therapy to help with muscle strength and stiffness, Occupational therapy to improve your ability to perform daily tasks, Speech therapy to help with any speaking and swallowing issues, Psychotherapy to help with mental health conditions, Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition. […] You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved ones condition. […] Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably with the medical, social and emotional support necessary to cope with a serious health condition.

• #60 Gene Therapy for Metachromatic Leukodystrophy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5027970/

  Leukodystrophies are rare white matter genetic disorders of the central nervous system (CNS) with progressive neurologic deterioration. One approach to the treatment of leukodystrophies is by gene therapy. […] Gene therapy using adeno-associated virus (AAV) is an ideal choice for clinical development as it provides the best balance of potential for efficacy with a reduced safety risk profile. In this review, we have summarized preclinical data that support the use of a gene therapy with the AAVrh.10 serotype for clinical development as a treatment for MLD. […] Various therapeutic approaches to MLD have been tested in experimental animal models. Among these there are several promising approaches with clinical translation potential, including: (1) enzyme-replacement therapy (ERT); (2) bone marrow transplants (BMT); (3) gene therapy by ex vivo transplantation of genetically modified hematopoietic stem cells (HSC); and (4) AAV-mediated gene therapy directly to the CNS.

• #61 Metachromatic leukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/symptoms-causes/syc-20354733

  There is no cure for metachromatic leukodystrophy yet. Depending on the form and age of onset, early identification and treatment may help manage some signs and symptoms and delay progression of the disorder. […] Beck M. Treatment strategies for lysosomal storage disorders. Developmental Medicine and Child Neurology. 2018; doi:10.1111/dmcn.13600. […] Rosenberg JB, et al. Gene therapy for metachromatic leukodystrophy. Journal of Neuroscience Research. 2016; doi:10.1002/jnr.23792. […] Adang LA, et al. Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies. Molecular Genetics and Metabolism. 2017; doi:10.1016/j.ymgme.2017.08.006.

• #62 Metachromatic leukodystrophy late infantile form | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/metachromatic-leukodystrophy-late-infantile-form/

  Is any research being done? […] Research is progressing in various areas concerning leukodystrophies and other progressive neurological disorders, particularly 'mapping’ genes and understanding which gene is responsible for what process with a view to gene therapy in the future. Work is also being done into how the missing enzyme could be replaced in the brain cells. Sadly, any treatment that could reverse the disease process is unlikely to be discovered quickly enough to help children who already have symptoms.

• #63 News: CRISPR-Edited Stem Cells Represent a New Prospective Treatment for Metachromatic Leukodystrophy – CRISPR Medicine

  https://crisprmedicinenews.com/news/crispr-edited-stem-cells-represent-a-new-prospective-treatment-for-metachromatic-leukodystrophy/

  For the first time, a team of scientists and medical doctors in Germany is exploring CRISPR to treat the rare genetic disorder Metachromatic leukodystrophy (MLD). […] These mutations have now been reversed in patient-derived haematopoietic stem and progenitor (HSPC) cells using CRISPR methodology, paving the way towards a new therapy for MLD. […] The results are promising: the edited cells display ARSA enzyme activity levels comparable to those seen in healthy individuals, and we are now working on advancing our findings as part of a stem cell gene therapy strategy for MLD, said Dr Justin S. Antony, first author of the study. […] Common treatment regimens for MLD include allogeneic HSPC transplantation or enzyme replacement, both of which are associated with low success rates. […] Enzyme replacement therapy must be administered every one or two weeks intrathecally by lumbar puncture to cross the blood-brain barrier.

• #64 News: CRISPR-Edited Stem Cells Represent a New Prospective Treatment for Metachromatic Leukodystrophy – CRISPR Medicine

  https://crisprmedicinenews.com/news/crispr-edited-stem-cells-represent-a-new-prospective-treatment-for-metachromatic-leukodystrophy/

  For the first time, a team of scientists and medical doctors in Germany is exploring CRISPR to treat the rare genetic disorder Metachromatic leukodystrophy (MLD). […] These mutations have now been reversed in patient-derived haematopoietic stem and progenitor (HSPC) cells using CRISPR methodology, paving the way towards a new therapy for MLD. […] The results are promising: the edited cells display ARSA enzyme activity levels comparable to those seen in healthy individuals, and we are now working on advancing our findings as part of a stem cell gene therapy strategy for MLD, said Dr Justin S. Antony, first author of the study. […] Common treatment regimens for MLD include allogeneic HSPC transplantation or enzyme replacement, both of which are associated with low success rates. […] Enzyme replacement therapy must be administered every one or two weeks intrathecally by lumbar puncture to cross the blood-brain barrier.

• #65 News: CRISPR-Edited Stem Cells Represent a New Prospective Treatment for Metachromatic Leukodystrophy – CRISPR Medicine

  https://crisprmedicinenews.com/news/crispr-edited-stem-cells-represent-a-new-prospective-treatment-for-metachromatic-leukodystrophy/

  Transplantation of lentiviral-modified stem cells that overexpress ARSA represents the most promising treatment so far, but only if applied before symptom onset. […] The treatments that are available until now have often not been successful, especially because treatment usually comes too late even if it starts in a pre-symptomatic stage. […] The integration of a mutation-free ARSA cDNA represents an elegant solution to potentially correct a disorder that can arise through hundreds of different mutations, as Dr Antony highlights: We decided to go for a universal approach whereby the same treatment modality can be applied to any MLD patient, regardless of the mutation(s) present. […] Using the new methodology, the patients would receive their own cells, circumventing the risks of allogeneic transplantation.

• #66 Metachromatic Leukodystrophy (MLD) and gene therapy: a game-changing treatment backed by NEJM—Timing Is Everything | EurekAlert!

  https://www.eurekalert.org/news-releases/1081556

  Most of the children treated before the onset of symptoms retained their ability to walk, whereas this was lost in the first years of life in all the children in the control group, who had not received gene therapy because they were already symptomatic or because they had been diagnosed when the therapy was not yet available. […] In the light of these data collected over 12 years, which confirm that the positive effects of gene therapy are maintained over time, it becomes a priority to diagnose the disease early so as to maximize the effectiveness of treatment. […] Thanks to research, we have a therapy available that can change the course of a serious and unfortunately fatal disease without intervention, but only effective if acted upon in time. […] Gene therapy is administered via a single infusion after chemotherapy to make room for the correct cells and is approved in the EU and the US.

• #67 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250425/Gene-therapy-offers-hope-for-children-born-with-metachromatic-leukodystrophy.aspx

  As far as cognitive development is concerned, we have observed a significant benefit in almost all treated patients, who continue to acquire new cognitive skills compared to the control group with severe cognitive impairment and loss of all ability to communicate. […] It is administered via a single infusion after chemotherapy to make room for the correct cells and is approved in the EU and the US. It is indicated for children with the late-infantile or juvenile-early-onset forms who have not yet manifested clinical signs of the disease, and for those with the juvenile-early-onset form who, although presenting the first clinical manifestations, are still able to walk independently and have not yet shown a decline in cognitive abilities. […] „Thanks to research, we have a therapy available that can change the course of a serious and unfortunately fatal disease without intervention, but only effective if acted upon in time. This is why it is essential to have a newborn screening test for MLD as soon as possible, in order to diagnose the disease when it has not yet manifested itself.”

• #68 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250425/Gene-therapy-offers-hope-for-children-born-with-metachromatic-leukodystrophy.aspx

  As far as cognitive development is concerned, we have observed a significant benefit in almost all treated patients, who continue to acquire new cognitive skills compared to the control group with severe cognitive impairment and loss of all ability to communicate. […] It is administered via a single infusion after chemotherapy to make room for the correct cells and is approved in the EU and the US. It is indicated for children with the late-infantile or juvenile-early-onset forms who have not yet manifested clinical signs of the disease, and for those with the juvenile-early-onset form who, although presenting the first clinical manifestations, are still able to walk independently and have not yet shown a decline in cognitive abilities. […] „Thanks to research, we have a therapy available that can change the course of a serious and unfortunately fatal disease without intervention, but only effective if acted upon in time. This is why it is essential to have a newborn screening test for MLD as soon as possible, in order to diagnose the disease when it has not yet manifested itself.”

• #69 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  With proactive, comprehensive medical care, affected individuals can avoid unnecessary suffering and complications to have the best quality of life possible. […] If an individual is not eligible for transplant, proactive multidisciplinary care is essential to provide the best quality of life possible. There are a variety of therapies, adaptive equipment, and medications available for this very purpose. […] Newborn screening for MLD is currently being validated in a medium-scale pilot study by University of Washington investigators. This would help in early detection of more individuals with MLD who could potentially benefit from transplant. […] All families and caregivers of individuals affected by Leukodystrophy, whether they qualify for transplant or not, should seek expert care through the Leukodystrophy Care Network, or LCN. […] Hunter’s Hope is committed to funding research for better treatments and a cure for MLD and other Leukodystrophies.

• #70 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy

  https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-children-with-metachromatic-leukodystrophy-302091811.html

  „MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. […] The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. […] In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. […] The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. […] Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. […] There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy.

• #71 FDA Approves Lenmeldy for Metachromatic Leukodystrophy

  https://www.asgct.org/publications/news/march-2024/libmeldy-metachromatic-leukodystrophy-stem-cell-ge

  This approval is so exciting because it provides a one-time treatment that will prevent much of the decline brought on by this disease. […] In clinical trials, treatment with Lenmeldy resulted in preservation of motor function and cognitive development in most patients compared to disease natural history with up to 12 years of follow-up (median 6.76 years). […] With more than a cumulative 250 patient-years of follow-up, treatment was generally well-tolerated, with no treatment-related serious adverse events or deaths.

• #72 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  The main difficulty in the treatment of diseases affecting the nervous system arises from the poor permeability of the BBB (blood-brain barrier), which restricts access of therapeutic compounds during systemic administration and results in low effectiveness of many therapeutic approaches. […] For pre-symptomatic patients, bone marrow transplantation (BMT) or hematopoietic stem cell (HSC) transplantation may be helpful, but the therapeutic potential of this procedure remains controversial. […] One of the first and most effective approaches to currently treat MLD is BMT and HSC transplantation (HSCT). […] However, cohort studies have showed that in patients with juvenile MLD, demyelination continues to progress after BMT in 31% of cases. […] In the case of HSCT, it has been reported that siblings with the juvenile form receiving transplantation after the onset of the first symptoms demonstrate significant decrease in psychomotor functions compared to before the onset of the disease.

• #73 MED.00148 Gene Therapy for Metachromatic Leukodystrophy

  https://provider.healthybluenc.com/dam/medpolicies/healthybluenc/active/policies/mp_pw_e003052.html

  There is no cure for MLD at this time. Current treatments include symptom management, physical and occupational therapy, and psychological and emotional support. Stem cell transplantation can be considered in pre-symptomatic or minimally symptomatic children. […] Gene therapy is a new approach for treating MLD. The first gene therapy for MLD, atidarsagene autotemcel (Lenmeldy, Orchard Therapeutics), was approved by the FDA in March 2024.

• #74 Metachromatic leukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/metachromatic-leukodystrophy/diagnosis-treatment/drc-20354734

  Other treatments may be needed as the condition progresses. Examples include a wheelchair, walker or other assistive devices; mechanical ventilation to assist with breathing; treatments to prevent or address complications; and long-term care or hospitalization. […] Care for metachromatic leukodystrophy can be complex and change over time. Regular follow-up appointments with a team of medical professionals experienced in managing this disorder may help prevent certain complications and link you with appropriate support at home, school or work. […] Potential treatments for metachromatic leukodystrophy that are being studied include: […] Gene therapy and other types of cell therapy that introduce healthy genes to replace diseased ones […] Enzyme replacement or enhancement therapy to decrease buildup of fatty substances […] Substrate reduction therapy, which reduces the production of fatty substances.

• #75 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Recently, the results of post-mortem brain tissue examination of two patients with MLD undergone HSCT and six patients without transplantation have been reported. […] Another approach similar to HSCT is cord blood cell transplantation (CBCT), since it is believed that cord blood cells more efficiently migrate to the CNS. […] Mesenchymal stem cells (MSCs) have also been tested in an attempt to find an effective treatment for MLD. […] A clinical case using MSCs in a 23-year-old woman with an adult form of MLD, which developed within 1 year with progressive neurological deterioration, has been described. […] Enzyme replacement therapy (ERT) was one of the first approaches used to increase the level of a normal enzyme, but it encountered a number of difficulties. […] The direct administration of viral vectors encoding the ARSA gene directly into the brain has been considered as a possible method of MLD therapy. […] Gene and combined gene-cell therapy are considered new promising methods for MLD therapy.

• #76 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  Other types of therapy may include: Physical therapy to help with muscle strength and stiffness, Occupational therapy to improve your ability to perform daily tasks, Speech therapy to help with any speaking and swallowing issues, Psychotherapy to help with mental health conditions, Percutaneous endoscopic gastronomy (PEF) to help with feeding issues and nutrition. […] You or your child may also wish to receive palliative care. Palliative care provides symptom relief, comfort and support to people living with serious conditions, including MLD. It also provides support to caregivers and those impacted by a loved ones condition. […] Palliative care complements the care you receive from the providers who help you manage MLD. It helps you live more comfortably with the medical, social and emotional support necessary to cope with a serious health condition.

• #77 Managing Metachromatic Leukodystrophy

  https://bephysiology.com.au/managing-metachromatic-leukodystrophy-mld/

  While MLD is a devastating and progressive disease, there are treatments and interventions available to help manage symptoms and improve quality of life. Incorporating regular exercise into a comprehensive treatment plan can help individuals with MLD maintain function and mobility for as long as possible.

Zobacz więcej