Materiały źródłowe

• #1 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. […] Most individuals with metachromatic leukodystrophy have mutations in the ARSA gene, which provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell’s recycling centers. Within lysosomes, arylsulfatase A helps break down sulfatides. […] A few individuals with metachromatic leukodystrophy have mutations in the PSAP gene. This gene provides instructions for making a protein that is broken up (cleaved) into smaller proteins that assist enzymes in breaking down various fats. One of these smaller proteins is called saposin B; this protein works with arylsulfatase A to break down sulfatides.

• #2 Metachromatic Leukodystrophy: Background, Pathophysiology, Epidemiology

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

  Metachromatic leukodystrophy (MLD) is part of a larger group of inherited lysosomal storage diseases, some of which are progressive and neurodegenerative disorders (MLD included). […] A deficiency in the lysosomal enzyme sulfatide sulfatase (arylsulfatase A [ARSA]) is present. […] Both defects result in the accumulation of sulfatide compounds in neural tissue and nonneural tissue, such as the kidneys and gallbladder, as well. […] These defects result from different gene mutations, mostly in the ARSA gene, and many new causative mutations have been identified. […] Phenotypic variation between siblings with MLD suggests that a number of biochemical and epigenetic factors contribute to the clinical phenotype.

• #3 List of Metachromatic Leukodystrophy Medications

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

  Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease characterized by the accumulation of sulfatides (fatty substances) in the cells, which causes damage to the central and peripheral nervous systems. […] MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene, which is responsible for encoding the enzyme arylsulfatase A (ARSA). A deficiency in ARSA leads to the buildup of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and spleen. […] The accumulation of sulfatides causes damage to the nervous system over time, leading to neurological problems such as motor, behavioral, and cognitive regression, severe spasticity, and seizures.

• #4 Metachromatic leukodystrophy | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20209443/

  Metachromatic leukodystrophy is an inherited disorder caused by an abnormal (mutated) gene. The condition is inherited in an autosomal recessive pattern. The abnormal recessive gene is located on one of the nonsex chromosomes (autosomes). To inherit an autosomal recessive disorder, both parents must be carriers, but they do not typically show signs of the condition. The affected child inherits two copies of the abnormal gene one from each parent. […] The most common cause of metachromatic leukodystrophy is a mutation in the ARSA gene. This mutation results in a lack of the enzyme that breaks down lipids called sulfatides that build up in the myelin. […] Rarely, metachromatic leukodystrophy is caused by a deficiency in another kind of protein (activator protein) that breaks down sulfatides. This is caused by a mutation in the PSAP gene. […] The buildup of sulfatides is toxic, destroying the myelin-producing cells also called white matter that protect the nerves. This results in damage to the function of nerve cells in the brain, spinal cord and peripheral nerves.

• #5 About MLD – ARCHANGEL

  https://archangel.org.uk/about-mld/

  Metachromatic leukodystrophy (MLD) is a rare genetically inherited disease that affects 0.001% of the population. […] Patients with MLD lack of an important enzyme called arylsulfatase A, which causes toxic material to build up and damage the myelin sheath covering the nerve fibres of the brain and nervous system. […] The disease is caused by defective genes. You must get a copy of a defective gene from both of your parents to have the disease. Parents can each have a defective gene, but not have MLD. […] The disease is passed down through families. You must get a copy of the defective gene from both your parents to have the disease. Parents can each have the defective gene, but not have MLD. […] Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.

• #6 Metachromatic leukodystrophy Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is a genetic disorder that affects nerves, muscles, other organs, and behavior. It slowly gets worse over time. […] MLD is usually caused by the lack of an important enzyme called arylsulfatase A (ARSA). Because this enzyme is missing, chemicals called sulfatides build up in the body and damage the nervous system, kidneys, gallbladder, and other organs. In particular, the chemicals damage the protective sheaths that surround nerve cells. […] The disease is passed down through families (inherited). You must get a copy of the variant gene from both of your parents to have the disease. Parents can each have one copy of the variant gene, but not have MLD. A person with one variant gene is called a carrier. […] Children who inherit only one variant gene from one parent will be a carrier, but usually will not develop MLD. When two carriers have a child, there is a 1 in 4 chance that the child will get both genes and have MLD.

• #7 Metachromatic Leukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560744/

  Metachromatic leukodystrophy is caused by deficient activity of arylsulfatase A. In almost all cases, mutations are in the arylsulfatase A gene (ARSA gene), on chromosome 22q13.3-qter. Two alleles, A and I have contributed to approximately 50 percent of cases and are responsible for different clinical expression of the disease. […] In some cases, it is due to the deficiency of sphingolipid activator protein SAP-B (saposin B), which is responsible for the degradation of sulfatides by ARSA. This form is caused by mutations in the prosaposin gene (PSAP gene).

• #8 Metachromatic Leukodystrophy | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25045

  Metachromatic leukodystrophy is caused by deficient activity of arylsulfatase A. In almost all cases, mutations are in the arylsulfatase A gene (ARSA gene), on chromosome 22q13.3-qter. Two alleles, A and I have contributed to approximately 50 percent of cases and are responsible for different clinical expression of the disease. […] In some cases, it is due to the deficiency of sphingolipid activator protein SAP-B (saposin B), which is responsible for the degradation of sulfatides by ARSA. This form is caused by mutations in the prosaposin gene (PSAP gene).

• #9 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. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively. […] MLD is caused by the deficiency of arylsulfatase A lysosomal enzyme (ARSA) (OMIM 250100) and sphingolipid activator protein B (SapB or saposin B) (OMIM 249900) as a consequence of mutations in the ARSA and PSAP genes, respectively. About 261 unique mutations in the ARSA gene and 64 unique mutations in the PSAP gene, leading to the development of MLD, are reported to date.

• #10 Metachromatic Leukodystrophy – MD Searchlight

  https://mdsearchlight.com/health/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is a condition that occurs when the body doesnt produce enough of an enzyme called arylsulfatase A. This deficiency is usually caused by genetic mutations in a specific gene (ARSA gene), located on chromosome 22q13.3-qter. […] Research has found that two variants of this gene known as A and I are found in about half of the cases and lead to different ways the disease shows up in individuals. […] In some instances, the condition isnt due to a lack of arylsulfatase A but another enzyme called saposin B (SAP-B). This enzyme helps breaking down certain fats called sulfatides. This particular form of the disease is caused due to mutations in a different gene, known as the prosaposin gene (PSAP gene).

• #11 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. […] Most individuals with metachromatic leukodystrophy have mutations in the ARSA gene, which provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell’s recycling centers. Within lysosomes, arylsulfatase A helps break down sulfatides. […] A few individuals with metachromatic leukodystrophy have mutations in the PSAP gene. This gene provides instructions for making a protein that is broken up (cleaved) into smaller proteins that assist enzymes in breaking down various fats. One of these smaller proteins is called saposin B; this protein works with arylsulfatase A to break down sulfatides.

• #12 Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1220-4

  Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease caused by deficient activity of the lysosomal enzyme arylsulfatase A (ASA). […] Its deficiency results in both excessive urinary excretion and intralysosomal accumulation of these sulfatides in various tissues (e.g. nervous tissue, gall bladder, kidneys and liver). […] The reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. […] Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. […] However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. […] The genetic and biochemical cause of MLD has facilitated the implementation of a series of clinical studies targeting HCT and gene therapy.

• #13 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  MLD is directly caused by a deficiency of the enzyme arylsulfatase A and is characterized by enzyme activity in leukocytes that is less than 10% of normal controls. […] Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system. […] A 2011 study contended sulfatide is not completely responsible for MLD because it is non-toxic. It has been suggested that lysosulfatide, sulfatide which has had its acyl group removed, plays a role because of its cytotoxic properties in vitro.

• #14 Metachromatic Leukodystrophy (MLD): Arylsulfatase A Enzyme Analysis – Greenwood Genetic Center

  https://ggc.org/test-finder-item/metachromatic-leukodystrophy-arylsulfatase-a-enzyme-analysis

  Metachromatic leukodystrophy is an autosomal recessive condition caused by a deficiency of arylsulfatase A, an enzyme crucial to the breakdown of sulfatides in the body. […] The accumulation of sulfatides causes demyelination of nerves.

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

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

  The PSAP (Gene/Locus MIM 176801) gene is located on chromosome 10q21.1 instead, and consists of 15 exons. The PSAP gene encodes a precursor protein, prosaposin (pSap), consisting of 524 amino acids. As a result of the cleavage of the precursor protein, four types of saposin are formed: SapA, SapB, SapC, and SapD. These saposins are sphingolipid activator proteins and are necessary for the functioning of some lysosomal enzymes.

• #16 Metachromatic Leukodystrophy (MLD) – United Leukodystrophy Foundation

  https://ulf.org/leukodystrophies/metachromatic-leukodystrophy-mld/

  Metachromatic Leukodystrophy (MLD) is inherited in an autosomal recessive manner, and is most commonly caused by a mutation in a gene called arylsulfatase A (ASA), also called sulfatide sulfatase. […] MLD can also be caused by a defect in Saposin B (also referred to as the cerebroside sulfate activator), which is a protein required for ASA to work properly. […] ASA is required for the breakdown of sulfatides, also called glycolipid- cerebroside sulfates, which are fats present in myelin. When ASA is deficient, the sulfatides build up in the myelin to high levels, disrupting the myelin structure and causing demyelination to occur in both the central nervous system and in the peripheral nervous system.

• #17 Metachromatic leukodystrophy | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/metachromatic-leukodystrophy?lang=us

  Metachromatic leukodystrophy (MLD) is the most common hereditary (autosomal recessive) leukodystrophy and is one of the lysosomal storage disorders. […] It arises from a deficiency of the enzyme arylsulfatase A as a result of a mutation in the arylsulfatase A (ARSA) gene located on chromosome 22q13. […] This results in the accumulation of 3-O-sulfogalactosylceramide (sulfatide) in various organs including the central nervous system (Schwann cells, oligodendrocytes, and some neurons) impairing myelination and function.

• #18 Novel in-frame duplication variant characterization in late infantile metachromatic leukodystrophy using whole-exome sequencing and molecular dynamics simulation | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282304

  Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal storage disease caused by a deficiency in the arylsulfatase A (ARSA). ARSA deficiency leads to sulfatide accumulation, which involves progressive demyelination. […] MLD is one of the lysosomal storage diseases (LSDs) with a prevalence of 1.45 per 100,000 births worldwide. MLD is a sphingolipidosis caused by lysosomal enzyme arylsulfatase A (ARSA) deficiency or its sphingolipid activator protein B (SapB). […] The ARSA gene is located on chromosome 22q13 with eight exons spanning a genomic region of 3kb and encoding a 509 amino acids. ARSA deficiency leads to an increase in the sulfatide within oligodendrocytes, macrophages, and some subtypes of neurons in the CNS, in Schwann cells, and in the peripheral nervous system (PNS) macrophages, which exhibit metachromatic staining characteristics.

• #19 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Mutations in the ARSA or PSAP genes result in a decreased ability to break down sulfatides, resulting in the accumulation of these substances in cells. Excess sulfatides are toxic to the nervous system. The accumulation gradually destroys myelin-producing cells, leading to the impairment of nervous system function that occurs in metachromatic leukodystrophy.

• #20 Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1220-4

  The observed increased g-ratios (ratio between axonal diameter and myelinated fiber diameter) suggest that the thick myelinated fibers are remodeled into thin myelinated fibers. […] Notably, Cravioto et al. also described several abnormalities other than inclusion bodies. […] These abnormalities could reflect a metabolic derangement of these cells, causing premature cell death, and may explain the lack of a correlation between demyelination and presence of metachromatic material. […] The lack of a correlation between demyelination and the presence of metachromatic material raises the question whether the pathology of peripheral neuropathy in MLD can be partially explained by a neuroinflammatory scenario. […] A hypothetical neuroimmune activation model leading to a vicious cycle of demyelination in MLD is proposed.

• #21 Leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Leukodystrophy

  When there is a mutation in the gene that encodes ASA, it decreases ASA production, which subsequently leads to diminished degradation of sulfatides, thus causing them to accumulate. […] This accumulation of sulfatides is toxic to oligodendrocytes, the myelin-producing cells of the CNS, effectively leading to a disturbance in myelin structure followed by demyelination.

• #22 MLD (metachromatic leukodystrophy) – GPnotebook

  https://gpnotebook.com/pages/neurology/mld-metachromatic-leukodystrophy

  Metachromatic leukodystrophy (MLD) is a lysosomal storage disease […] disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency […] ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively […] severity of clinical course in metachromatic leukodystrophy is determined by the residual ARSA activity, depending on the type of mutation […] MLD causes demyelination to occur, leading to impaired motor function, spastic tetraparesis, ataxia, spasms, optic atrophy, and cognitive impairment […] however, the exact mechanisms of demyelination in MLD remain unknown.

• #23 Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1220-4

  However, the striking variation in MLD phenotypes, even within subtypes and families, hampers the possibility to generalize treatment outcomes. […] In general, it appears that asymptomatic patients with juvenile and adult MLD experience a clear symptomatic and survival benefit from allogeneic HCT; however, this benefit is transient and often limited to the CNS symptoms. […] Preliminary studies show that PNS symptoms in patients respond better to gene therapy, most likely due to higher enzyme levels achieved than with HCT and thereby increased penetration into the peripheral nerves. […] The use of autologous hematopoietic stem cells transduced with a lentiviral vector containing a healthy copy of the ARSA gene allows supra-normal production (5001000%) of ASA by donor cells, due to overexpression of the gene by a stronger promoter.

• #24 Metachromatic leukodystrophy (MLD) | Britannica

  https://www.britannica.com/science/metachromatic-leukodystrophy

  metachromatic leukodystrophy (MLD), rare inherited metabolic disease in which the lack of a key enzyme causes loss of the protective myelin sheath from the white matter of the brain, resulting in psychological disturbances, mental deterioration, and sensory and motor defects. […] A number of genetic mutations have been associated with MLD. Nearly all of these mutations occur in a gene known as ARSA (arylsulfatase A) and result in outright or partial loss of activity of the gene product, an enzyme called arylsulfatase A (ASA), or cerebroside sulfatase. Arylsulfatase A deficiency allows certain harmful sulfur-containing lipids, known as sulfosphingolipids (also called sulfatides), to accumulate in nerve tissues of the central nervous system instead of being broken down. […] Specific mutations in ARSA are linked to the timing of MLD onset and the phenotypic patterns (physical manifestations) of MLD, such as the degree of ASA deficiency and the severity of neuropsychiatric symptoms. Other genetic defects, such as those leading to the deficiency of an activator protein involved in the degradation of sulfatides but in which patients have normal ASA levels, can also cause MLD. […] In addition, there exist individuals who have very low levels of ASA but never develop the disease. This condition is known as pseudoarylsulfatase A deficiency (PASAD) and is the result of two specific polymorphisms that occur simultaneously in the ARSA gene.

• #25 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  In terms of laboratory exams, according to Van Rappard et al., the examination of the Arylsulfatase A enzyme activity should not be the only parameter since this may be low in cases of pseudo-deficiency of MLD alleles, which is caused by low enzyme activity but the patient presents no symptoms. […] With the examination of urine sulfatdes it is possible to distinguish it from actual ARSA deficiency since, if the results are positive, MLD is confirmed. […] Even though there is still no curative treatment for this disease, new therapeutic possibilities are emerging, such as intrathecal enzyme replacement and hematopoietic stem-cell transplantation (HSCT) associated with gene therapy. […] HSCT aims to treat the manifestations of MLD in the central nervous system; however, there are obstacles that still prevent it from being timely offered to patients because it preferably should be performed in a pre-symptomatic or oligosymptomatic phase with an allogeneic donor.

• #26

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/07000/metachromatic_leukodystrophy_in_infant_presenting.55.aspx

  Metachromatic leukodystrophy (MLD) is a rare genetic disorder affecting the central and peripheral nervous systems. It results from ARSA enzyme deficiency, causing sulfatide accumulation and myelin damage. […] MLD 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. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB). […] The absence of arylsulfatase A (ARSA) enzymes leads to sulfatide accumulation, which damages myelin in the central and peripheral nervous systems, resulting in the loss of motor and cognitive skills. […] MLD is one of the most common leukodystrophies and has a prevalence rate of 1 in 40,000 to 160,000 worldwide.

• #27 The importance of early diagnosis and views on newborn screening in metachromatic leukodystrophy: results of a Caregiver Survey in the UK and Republic of Ireland | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-022-02550-z

  Metachromatic Leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). […] The rapid rate of deterioration in MLD makes it an essential candidate for NBS, particularly now the first gene therapy (Libmeldy) has been approved by the European Medicines Agency. […] The prevalence of MLD is estimated at 1.1 cases per 100,000 live births in the EU. […] The exact definition of the different subtypes may vary slightly between sources, although broadly speaking, the most common subtype, late infantile MLD, occurs in the first two years of life. […] Diagnosis of MLD is challenging due to the broad spectrum of symptoms and their overlap with other diseases and conditions. […] MLD is currently diagnosed by biochemical testing using mass spectrometry to quantify sulfatides in dried blood and urine spots. […] Currently, most management is focused on palliative care, although haematopoietic stem cell transplantation (HSCT) is available. […] The rapid rate of disease progression MLD makes it an essential candidate for NBS, particularly now as the first gene therapy has been approved.

• #28

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/07000/metachromatic_leukodystrophy_in_infant_presenting.55.aspx

  MLD takes its name from the presence of metachromatic granules in the affected cells, formed as a result of the accumulation of sulfatides and sphingolipids presented in myelin. […] In most cases, MLD is not included in the fetus and newborn genetic screening tests given that MLD is a rare disease. […] Early diagnosis plays a pivotal role in managing MLD. […] This underscores the importance of considering rare diseases in cases of unexplained neurological regression in children. […] Regrettably, this case highlights the dearth of effective treatments for MLD. […] There are no fully curative therapies for MLD, but early MLD is a treatable disease. […] Allogeneic hematopoietic cell transplantation (HSCT) is the first-line treatment option offered for eligible patients. […] This case report is a poignant illustration of the challenges of rare genetic diseases like MLD.

• #29 Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/90/5/543

  Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused mainly by deficient activity of arylsulfatase A (ARSA). ARSA is responsible for the desulfation of cerebroside sulfate, a major glycolipid of myelin, and decreased ARSA activity leads to the accumulation of cerebroside sulfate in the CNS and peripheral nerves (as well as the kidneys and other visceral organs). The result is central and peripheral demyelination. […] In almost all cases, recessive mutations in the ARSA gene are responsible, although very rarely, MLD can be caused by mutations in the PSAP gene. […] Diagnosis is established by demonstrating deficient ARSA activity in leucocytes (white cell enzyme testing) or cultured skin fibroblasts. […] No curative treatment is currently available, but HSCT has slowed disease progression in some patients. Other promising novel treatments include gene therapy and enzyme replacement.

• #30 SciELO Brazil – Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis

  https://www.scielo.br/j/ramb/a/4Tcf3mYwRfLMdxkTzwXxT5q/

  Recently, advances have allowed combining HSCT with gene therapy. […] Gene therapy is the delivery of genetic material, using viral vectors, to the cells or tissues of an individual for therapeutic purposes. […] Enzyme replacement therapy (ERT) is an alternative that benefits from the enzyme provision via the intrathecal route in patients with the late infantile presentation.

• #31 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

  Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. It is caused by a deficiency of an enzyme called arylsulfatase A (ARSA), leading to a buildup of sulfatides (fatty substances) in the cells. […] This buildup causes damage to the central and peripheral nervous system, manifesting with loss of motor and cognitive function and early death. […] There is no cure for MLD, and treatment typically focuses on supportive care and symptom management.

• #32 Metachromatic Leukodystrophy – A Rare Indication unmet medical need

  https://www.delveinsight.com/blog/metachromatic-leukodystrophy-mld-rare-indication-great-unmet-medical-need

  Metachromatic Leukodystrophy (MLD) is a rare lysosomal storage disease which is genetic, degenerative, neurometabolic in nature. […] Patients suffering from MLD are deficient in the arylsulfatase-A enzyme, which is responsible for breaking down fatty substances called sulfatides into harmless chemicals. […] A person with MLD cannot break down these sulfatides, causing them to accumulate in the body. […] This accumulation causes the destruction of myelin (demyelination), which is the protective covering on the nerve fibers that enables communication between the nerves and the brain. […] As Metachromatic Leukodystrophy is a genetic disorder, companies are however intent on exploring technologies related to Gene Therapy, Cell therapy, and Enzyme technology while certain institutions are also working relentlessly towards exploring new treatment scenarios.

• #33 Metachromatic Leukodystrophy – A Rare Indication unmet medical need

  https://www.delveinsight.com/blog/metachromatic-leukodystrophy-mld-rare-indication-great-unmet-medical-need

  At present, controlling the expression of malfunctioning gene as well as modulating the activity of ARSA enzyme is the only currently available treatment that can provide some ray of hope for treating this untreated indication while new research output may provide a much-needed boost for patients suffering from this genetic condition.

• #34 From Research to Reality: Gene Therapy for Metachromatic Leukodystrophy – ACCESS Health International

  https://accessh.org/from-chairs-desk/from-research-to-reality-gene-therapy-for-metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is a rare genetic disorder that affects the nervous system. This condition is caused by a deficiency of the lysosomal enzyme arylsulfatase A (ARSA), which breaks down sulfatides in the body. […] When ARSA levels are low, sulfatides build up in the body and cause progressive demyelination of the central and peripheral nervous systems.

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