Materiały źródłowe

• #1 Adrenoleukodystrophy | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/adrenoleukodystrophy?content_id=CON-20369148

  Adrenoleukodystrophy has no cure. However, stem cell transplantation may stop the progression of ALD if done when neurological symptoms first appear. Doctors will focus on relieving your symptoms and slowing disease progression. […] Treatment options may include: […] Stem cell transplant. This may be an option to slow or halt the progression of adrenoleukodystrophy in children if ALD is diagnosed and treated early. Stem cells may be taken from bone marrow through bone marrow transplant. […] Adrenal insufficiency treatment. Many people who have ALD develop adrenal insufficiency and need to have regular adrenal gland testing. Adrenal insufficiency can be treated effectively with steroids (corticosteroid replacement therapy). […] Medications. Your doctor may prescribe medications to help relieve symptoms, including stiffness and seizures.

• #2 An update on the diagnosis and treatment of adrenoleukodystrophy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36373727/

  Purpose of review: The present review summarizes recent advances in the diagnosis and management of patients with X-linked adrenoleukodystrophy (ALD). […] Hematopoietic stem cell transplant (HSCT) remains the only successful treatment option available for early cerebral ALD but does not reverse neurological changes or affect the course of adrenal insufficiency. […] Novel therapies such as gene therapy and gene editing have shown promising results in animal models and are exciting potential treatment options for the future. […] Early diagnosis and HSCT are key to improving the morbidity and mortality associated with ALD. The implementation of universal newborn screening for ALD and rigorous investigations of novel diagnostic and therapeutic agents is the need of the hour.

• #3 Adrenoleukodystrophy (ALD) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/adrenoleukodystrophy-ald

  Gene therapy treatment for adrenoleukodystrophy (ALD) is now called SKYSONA, which was developed to stop the disease progression and highlights the importance of early diagnosis. […] The good news is that there are treatments for CALD, including a new gene therapy, that can halt the decline in brain function in CALD and allow children to thrive if given early enough. […] If CALD is diagnosed early enough before neurologic symptoms develop or while symptoms are still very mild there are two very effective treatments: gene therapy and hematopoietic stem cell transplant. […] A gene therapy for CALD called SKYSONA (elivaldogene autotemcel) has now been approved by the U.S. Food and Drug Administration. This treatment is for boys with CALD who are experiencing few or no symptoms. […] Studies have found that when gene therapy is given early enough, it can prevent or minimize damage to the brain and disability caused by CALD.

• #4 Treating ALD — The Stop ALD Foundation

  http://www.stopald.org/treating-ald

  Boys with ALD who have a Loes score lower than 8 or 9 (an MRI measure of the severity of the disease) are generally considered candidates for stem cell transplantation. There are currently two sources for transplanted stem cells: umbilical cord blood (UCBT) or bone marrow (BMT). In both cases, the goal is to provide the patient with healthy stem cells that produce a functioning ALD protein — the protein that is lacking in people with ALD. Scientists believe that this works as some portion of the donated cells, which are not genetically defective, find their way into the brain, express the missing or nonfunctioning ALD protein, and halt or even reverse the brain damage. […] Although much of this theory remains to be scientifically proven, these transplants have been successful; among the small number of patients who have had transplants, some have had their condition stabilize, and a few even made slight improvements. But there is a very narrow window in which stem cell transplantation appears to be effective — the time between when the brain lesions appear on an MRI, and when the boy first starts showing symptoms.

• #5 Treating Cerebral ALD

  https://www.itmightbeald.com/cerebral-ald-treatment

  Currently, the only treatment for cerebral adrenoleukodystrophy (ALD) that can stabilize disease progression is allogeneic hematopoietic stem cell transplantation (allo-HSCT) and it can be lifesaving. Early diagnosis during the first signs of cerebral involvement is critical because outcomes with allo-HSCT are more favorable with earlier initiation of treatment. […] Treatment early in the course of cerebral disease demonstrated greater major function disability (MFD) -free survival and overall survival. […] Allo-HSCT can stabilize disease progression if performed during the early stage of cerebral involvement, but it has significant associated risks. These include transplant-related mortality (TRM), graft failure or rejection, graft-versus-host disease (GVHD), and the potential for opportunistic infections.

• #6 Treating ALD — The Stop ALD Foundation

  http://www.stopald.org/treating-ald

  This treatment also has serious risks. Both types of transplantation require that the patient’s immune system essentially be wiped out by high-dose chemotherapy and/or radiation, so that their bodies do not reject the foreign donor cells. This leaves patients vulnerable to almost any kind of infection, and these procedures have a mortality rate that is as high as 40%. It can also be difficult to find a well-matched donor, and sometimes the donor cell graft does not „take.” […] Unfortunately, there also appears to be a period of about six to eighteen months following transplant when the disease progression continues. This means that, even in a best case scenario, the child emerging from this medical procedure will have more advanced brain damage than he had going in. If the downward slide is then arrested by the transplant, this may be a trade-off worth making. But in boys suffering from a late diagnosis, often a BMT will only rapidly advance their condition into a completely vegetative state.

• #7 Stanford Medicine offers gene therapy for a devastating pediatric neurologic disease | News Center

  https://med.stanford.edu/news/all-news/2024/06/adrenoleukodystrophy-therapy.html

  Experts at Stanford Medicine Children’s Health helped conduct clinical trials for the new therapy, which gives kids with X-linked adrenoleukodystrophy, or ALD, a functioning copy of the abnormal gene. […] The new therapy, approved by the U.S. Food and Drug Administration in late 2022, halts brain complications of the genetic disease more commonly known as ALD. […] Stanford Medicine experts helped conduct the clinical trial that enabled FDA approval for the new therapy, which is called elivaldogene autotemcel (marketed as Skysona and made by Bluebird Bio). […] „What’s exciting about this new treatment is that patients do not go through the toxicity of a typical transplant,” said Ami Shah, MD, clinical professor of pediatrics, who led the Stanford Medicine arm of the clinical trial. […] In the new gene therapy treatment, instead of transplanting stem cells from another person, the patient’s own stem cells are removed, modified to insert the missing gene, then returned to them.

• #8 Stanford Medicine offers gene therapy for a devastating pediatric neurologic disease | News Center

  https://med.stanford.edu/news/all-news/2024/06/adrenoleukodystrophy-therapy.html

  „With this option, there is less chemotherapy and zero risk of graft-versus-host disease,” Shah said. […] Stanford Medicine is currently the only site west of the Mississippi equipped to administer the new therapy. […] Catching these signs quickly gives patients the best chance for successful treatment with a stem cell transplant or gene therapy, as these approaches can stop the brain complications from worsening but don’t reverse brain damage that has already occurred. […] Five years later, when Ivan needed treatment, his physician recommended the gene therapy clinical trial. […] The family was thrilled when they learned that the process carried a much lower risk of complications. […] Medical care for ALD has been gradually improving since the first stem cell transplant for the condition was performed in the early 1980s, but commercially available gene therapy treatment still has uncertainties, Shah noted.

• #9 Adrenoleukodystrophy | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/adrenoleukodystrophy?content_id=CON-20369148

  Physical therapy. Physical therapy may help relieve muscle spasms and reduce muscle rigidity. Your doctor may recommend wheelchairs and other mobility devices if needed. […] In a recent clinical trial, boys with early-stage cerebral ALD were treated with gene therapy as an alternative to stem cell transplantation. Early results from gene therapy are promising. Disease progression stabilized in 88 percent of boys who participated in the trial. Additional research is necessary to assess long-term results and safety of gene therapy for cerebral ALD.

• #10 Gene Therapy Halts Progression of Cerebral Adrenoleukodystrophy in Clinical Trial | Dana-Farber Cancer Institute

  https://blog.dana-farber.org/insight/2017/12/gene-therapy-halts-progression-of-cerebral-adrenoleukodystrophy-in-clinical-trial/

  Adrenoleukodystrophy depicted in the 1992 movie Lorenzos Oil is a genetic disease that most severely affects boys. […] But now, a breakthrough treatment is offering hope to families affected by adrenoleukodystrophy. A gene therapy treatment effectively stabilized CALDs progression in 88 percent of patients, according to clinical trial results reported in the New England Journal of Medicine. […] In the clinical trial, sponsored by bluebird bio, 15 of 17 patients had stable neurologic functioning more than two years after receiving the gene therapy. […] Although we need to continue to follow the patients to determine the long-term outcome of the gene therapy, so far it has effectively arrested the progress of cerebral adrenoleukodystrophy in these children, says David A. Williams, MD, chief scientific officer and senior vice-president for research at Boston Childrens Hospital, president of Dana-Farber/Boston Childrens Cancer and Blood Disorders Center and the lead author of the study.

• #11 Gene Therapy Halts Progression of Cerebral Adrenoleukodystrophy in Clinical Trial | Dana-Farber Cancer Institute

  https://blog.dana-farber.org/insight/2017/12/gene-therapy-halts-progression-of-cerebral-adrenoleukodystrophy-in-clinical-trial/

  The treatment leverages bluebird bios proprietary Lenti-D gene therapy to deliver the functional gene to patients stem cells in the laboratory. […] Until now, stem cell transplantation using cells donated by another person has been the only known effective therapy for CALD. […] There are two great advantages to gene therapy, Williams says. The first is that patients dont have to wait to find a donor match. The second is that, because we use their own, gene-modified stem cells, theres no risk of graft-versus-host-disease and the patients do not require any immunosuppression drugs, which can have very significant, even fatal, side effects. […] In my clinic, the impact of this trial has been phenomenal, Eichler says. Boys without a donor match for stem-cell transplant were often passing away within a year or two of their diagnosis. Now, with early diagnosis and gene therapy, these boys are living longer and some are thriving enough to play sports and participate in other normal day-to-day activities. […] At the latest follow-up, all patients who participated in the clinical trial were expressing functional ALD protein, which their bodies had been unable to produce prior to gene therapy.

• #12 Stanford Medicine offers gene therapy for a devastating pediatric neurologic disease | News Center

  https://med.stanford.edu/news/all-news/2024/06/adrenoleukodystrophy-therapy.html

  However, given the severe and potentially fatal course of untreated cerebral ALD, experts who reviewed the treatment for FDA approval decided the risk was manageable, she added. […] Gene therapy treatment is expensive, at around $3 million, but U.S. health insurers have agreed to cover it, said Shah, adding that the treatment is not available in Europe because of the cost.

• #13

  https://link.springer.com/article/10.1016/j.nurx.2006.01.004

  Current therapies for X-linked adrenoleukodystrophy (X-ALD) include replacement therapy with adrenal steroids, which is mandatory for all patients with impaired adrenal function but does not alter neurological progression significantly; dietary therapy with Lorenzos Oil, which appears to have a preventive effect in asymptomatic boys whose brain MRI is normal; and hematopoietic stem cell transplantation in patients in the early stage of the cerebral inflammatory phenotype. […] Application of these interventions requires careful assessment of the patients phenotype, which often changes over time. Family screening provides important opportunities for disease prevention.

• #14 Adrenoleukodystrophy (ALD) |

  https://www.huntershope.org/family-care/leukodystrophies/adrenoleukodystrophy/

  Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 17,000 people. […] Although there is currently no cure for adrenoleukodystrophy, the symptoms can be managed to ensure the best possible outcomes. With proactive, comprehensive medical care the symptoms of ALD can be managed and give the individual the best quality of life possible. […] Through ALD Newborn Screening, affected children have the opportunity to benefit from lifesaving treatment. While treatment through a cord blood/stem cell transplant can slow the progression of the disease, it is not considered a cure. […] Approximately 90% of boys with ALD will also have adrenal insufficiency, or Addison’s Disease, which occurs when the adrenal glands do not produce enough of certain hormones. […] While ALD usually does not present before the age of 3, adrenal insufficiency can present within the first year of life. Therefore, it is extremely important to test blood ACTH and cortisol levels. Adrenal insufficiency can be treated easily by replacing or substituting the hormones the adrenal glands are not making with daily steroids.

• #15 Adrenoleukodystrophy Information | Mount Sinai – New York

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

  Adrenal dysfunction may be treated with steroids (such as cortisol) if the adrenal gland is not producing enough hormones. […] A specific treatment for X-linked ALD is not available. A bone marrow transplant may stop worsening of the condition. […] Supportive care and careful monitoring of impaired adrenal gland function may help in improving comfort and quality of life.

• #16 Adrenal insufficiency and the use of mineralocorticoid treatment in male patients with adrenoleukodystrophy; a retrospective analysis of an institutional database | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-024-01712-3

  Adrenoleukodystrophy (ALD) patients exhibit three primary clinical phenotypes: primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral demyelination due to the accumulation of saturated very long-chain fatty acids in the adrenal cortex and central nervous system white matter and axons. We investigated the diagnosis of adrenal insufficiency (AI) and the use of mineralocorticoid treatment in male ALD patients. […] Of the male ALD patients, 60% (213 out of 358) had a diagnosis of AI, and 39% (84 out of 213) of those with AI were prescribed mineralocorticoid replacement therapy. […] AI is highly prevalent among ALD patients, with approximately 40% of those with a diagnosis of AI undergoing mineralocorticoid replacement therapy. […] Approximately 40% of AI and ALD patients received mineralocorticoid replacement therapy, which could be due to the preferential VLCFA accumulation in the zona reticularis and zona fasciculata of the adrenal cortex, while sparing the zona glomerulosa. The treatment of adrenal insufficiency in patients with adrenoleukodystrophy (ALD) is similar to other patients with primary adrenal insufficiency, involving the replacement of glucocorticoids. However, unlike other patients with primary adrenal insufficiency, those with ALD may not always require mineralocorticoid replacement, as the loss of mineralocorticoid function is not universal in these patients.

• #17 Treating ALD — The Stop ALD Foundation

  http://www.stopald.org/treating-ald

  Clearly, the decision to pursue a bone marrow transplant is not an easy one and cannot be made lightly. […] Lorenzo’s oil is a combination of two fats extracted from olive oil and rapeseed oil. It was developed by Augusto and Michaela Odone to treat their son, Lorenzo, after he was diagnosed with ALD in 1982. The mixture of fatty acids in Lorenzo’s oil works to reduce the levels of very long chain fatty acids, which are known to cause ALD. […] Recent studies indicate that Lorenzo’s oil may be effective in staving off the onset of symptoms in boys with the disease who have not yet become symptomatic. A study published in theArchives of Neurology in July 2005 followed 89 boys with ALD who took Lorenzo’s oil and ate a low-fat diet. The boys had normal MRIs and no symptoms of ALD, but had been screened for the disease because they had an affected relative. After an average follow-up of seven years, 74% of the boys still had normal MRIs and no neurological symptoms.

• #18 Adrenoleukodystrophy in Children: Diagnosis and Treatment

  https://www.massgeneral.org/children/adrenoleukodystrophy/diagnosis-treatment

  How Do Doctors Treat Adrenoleukodystrophy? Treatment depends on a person’s symptoms and the type of adrenoleukodystrophy that they have. It is important to diagnose the disorder early so treatment will work better. Your child’s doctor will help figure out the best treatment. […] There are two aspects to treatment: […] Steroid replacement therapy. This is necessary when the adrenal glands are damaged and can no longer make the adrenal hormones cortisol and aldosterone. […] Lorenzo’s Oil. Along with reduced fat intake, Lorenzo’s oil has been used to reduce the risk of progression of the severe cerebral form of the disease […] Stem cell transplant. Stem cells are cells from bone marrow (soft core of bones) that can help make more protein from the ABCD1 gene.

• #19 Treating ALD — The Stop ALD Foundation

  http://www.stopald.org/treating-ald

  This study does not definitively prove that Lorenzo’s oil is what kept the boys from developing symptoms. It is possible that the boys who did not develop symptoms would not have developed the disease in childhood anyway, and they all could still develop adrenomyeloneuropathy (the later-onset form of the disease) when they reach adulthood. […] Nonetheless, the study’s results are encouraging. Parents with a child who may be at risk for ALD can inquire about enrolling in a clinical trial at the Kennedy Krieger Institute, 800-873-3377. That is presently the only way to obtain Lorenzo’s oil in the U.S. Since it is not approved by the Food and Drug Administration and still considered an experimental drug, not all insurance companies will provide coverage for the oil, which costs over $400 for a month’s treatment.

• #20 Adrenoleukodystrophy Clinical Practice Guidelines – 2022 Guideline Summary for Adrenoleukodystrophy

  https://www.guidelinecentral.com/guideline/2306198/

  To treat cerebral ALD, consult an ALD transplantation expert who can determine allogeneic or genetically transduced autologous stem cell transplantation eligibility. […] Treatment is supportive. Aim treatment at reducing pain and spasticity and maintaining functional ability and quality of life. […] Data to support the efficacy of Lorenzo’s oil as a disease-modifying treatment in patients with ALD are insufficient. […] Transplantation eligibility should be determined by an ALD transplantation expert. […] Genetically transduced autologous stem cell transplantation (gene therapy) should be considered (if available) in boys if allogeneic donor options are poor. […] If adrenal insufficiency is present, we recommend glucocorticoid replacement therapy by an endocrinologist. […] Mineralocorticoid replacement therapy should not be initiated based on symptoms alone but should also take into account plasma renin and serum electrolyte abnormalities. […] Data to support the efficacy of Lorenzo’s oil as a disease-modifying treatment in patients with ALD is insufficient.

• #21 Adrenoleukodystrophy (ALD) |

  https://www.huntershope.org/family-care/leukodystrophies/adrenoleukodystrophy/

  Once a boy is diagnosed with cerebral ALD, it is crucial to undergo prompt evaluation in order to evaluate eligibility for a bone marrow transplant. […] The oil is still considered experimental and may have some benefit in normalizing the VLCFA (Very Long Chain Fatty Acids), which may prevent the childhood cerebral form of ALD. […] For men with Adrenolmyeloneuropathy, methods of care consist of rehabilitation therapy, symptomatic medications for pain and stiffness, creating a diet and exercise regimen for ideal health. […] The FDA approved bluebird bio’s gene therapy treatment for childhood cerebral ALD on September 16, 2022. Gene therapy is a treatment option for children with cerebral ALD that offers an alternative to allogeneic hematopoietic stem cell transplant, eliminating the need for a bone marrow match.

• #22 Paramedical Treatment for Adrenoleukodystrophy (ALD)

  https://adrenoleukodystrophynews.com/2021/02/03/paramedical-treatment-adrenoleukodystrophy/

  Occupational therapists can work with patients to find easier ways to perform daily tasks, such as getting dressed, and may help patients maintain mobility and overall independence. […] For all patients with such issues, speech therapy may help. […] Massage, particularly of the hands and feet, can help improve circulation, stimulate the nerves, and even temporarily relieve pain. […] There has been at least one report of an ALD patient in Korea who was treated with acupuncture, which may have had an effect on the management of his disease.

• #23 What is the treatment of Adrenoleukodystrophy? | OnlyMyHealth

  https://www.onlymyhealth.com/what-treatment-adrenoleukodystrophy-12977604265

  Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the Leukodystrophies. Symptomatic and supportive treatments for Adrenoleukodystrophy include physical therapy, psychological support, and special education. […] In all patients with ALD, adrenal function must be tested periodically. The treatment with adrenal hormones can be lifesaver. The symptomatic and supportive treatment options are physical therapy, psychological support and special education. There is scientific evidence to suggest that a mixture of oleic acid and erucic acid, known as „Lorenzo’s Oil,” can reduce or delay the appearance of symptoms. Bone marrow transplants can provide long-term benefits. The treatment options also carry the risk of mortality and morbidity. In some cases, oral administration of docosahexanoic acid (DHA) may help infants and children with neonatal ALD.

• #24 Research & Clinical Trials — The Stop ALD Foundation

  http://www.stopald.org/current-treatment-research

  Scientists are still searching for comprehensive treatments for ALD and AMN. For the ALD cerebral onset, an approach is needed that would overcome some of the limitations and risks of stem cell transplantation and offer a wider therapeutic window than current transplantation or Lorenzos oil. For AMN, the adult version of ALD, options are needed to help with symptoms and prevent further deterioration. […] One of the most promising treatments on the horizon for ALD is gene therapy. This involves inserting the corrected genetic sequence with the appropriate blueprints into cells. The repaired cells will then produce the ALD protein that had been missing or defective prior to treatment, and the disease process will halt or moderately reverse. […] Successful gene therapy would yield the same positive results of stem cell transplantation, for many more patients, with far fewer risks.

• #25 Research & Clinical Trials — The Stop ALD Foundation

  http://www.stopald.org/current-treatment-research

  Other new treatment options, that may provide hope even after the disease has begun to ravage the brain, are also being studied. In early 2007, scientists from the University of Minnesota reported that treatment with a drug called Mucomyst (acetylcysteine), appears to provide protection from rapid neurological decline in the advanced form of ALD. […] Other possibilities now being studied by scientists funded by the Foundation include ALDR upregulation, in which a gene very similar to the ALD gene, which already exists in a normal form in people with ALD, could be upregulated. […] Scientists at several institutions are studying the use of mesenchymal stem cells (MSCs) in treating ALD. […] The Myelin Project is pursuing research into therapies that could actually restore the lost myelin, potentially reversing the damage done by the disease. […] Several agents are being investigated.

• #26 Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy in compassionate-use study published in Brain

  https://www.minoryx.com/media/leriglitazone_halts_disease_progression_in_adult_patients_with_early_cerebral_adrenoleukodystrophy_in_compassionate-use_study_published_in_brain/

  Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy in compassionate-use study published in Brain. […] In a French early-access program study, 10 of 13 patients were clinically and radiologically stable. […] The compassionate-use study was led by Fanny Mochel, MD, Ph.D., professor at the Hôpital Universitaire La Pitié-Salpêtrière (Paris, France), as part of an early-access program through the French national drug agency (ANSM) that allows for the use of innovative treatments with favorable safety profiles under a Compassionate Access Authorization protocol (ATU). […] Among the 13 patients treated with leriglitazone, the disease stabilized clinically and in radiological tests in 10 patients through up to two years of follow-up. […] Leriglitazone was well tolerated in all patients, with minimal weight gain in most patients and moderate leg edema in only two patients.

• #27 Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy in compassionate-use study published in Brain

  https://www.minoryx.com/media/leriglitazone_halts_disease_progression_in_adult_patients_with_early_cerebral_adrenoleukodystrophy_in_compassionate-use_study_published_in_brain/

  This cohort study shows that leriglitazone can halt neuroinflammation and disease progression in adult patients with cALD at early disease stages, as evidenced by clinical, radiological, and biological stability for up to two years of treatment, said Prof. Mochel. […] The results are very encouraging and support the efficacy of leriglitazone that we have observed in our clinical trials, ADVANCE and NEXUS. […] In consultation and alignment with the U.S. Food and Drug Administration, Minoryx has launched a phase 3 clinical trial (CALYX) in patients with adult progressive cALD that have a profile similar to those treated at Hôpital Universitaire La Pitié-Salpêtrière. […] NEZGLYAL (leriglitazone) is Minoryx Therapeutics novel orally bioavailable and selective PPAR gamma agonist with a potential first-in-class and best-in-class profile for CNS diseases.

• #28 ALD – Adrenoleukodystrophy – Alex – The Leukodystrophy Charity

  https://alextlc.org/condition/adrenoleukodystrophy-ald/

  The NHS clinical commissioning policy recommends that Allo-HSCT is available as a routinely commissioned treatment option for adult patients with C-ALD within the criteria set out in this document. […] New Born Screening for ALD would allow more boys with ALD to receive treatment before the condition progresses. This has been introduced in parts of the USA, and Alex TLC are actively involved in efforts to introduce it in the UK.

• #29 Adrenoleukodystrophy (ALD) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/adrenoleukodystrophy-ald

  The SKYSONA treatment is currently available for early, active CALD. […] Stem cell transplant from a genetically matched donor is an established, lifesaving option for CALD that can halt progression of the disease. […] As with gene therapy, early treatment is crucial; it unfortunately is not effective when disease is already advanced. […] Stem cell transplant and gene therapy each have pros and cons that your care team can discuss with you.

• #30 Gene therapy for ALD: Matthew’s story – Boston Children’s Answers

  https://answers.childrenshospital.org/first-gene-therapy-ald-recipient/

  With limited treatment options for ALD, doctors recommended a bone marrow transplant for Marc, using healthy blood stem cells from a donor to replace his diseased bone marrow. […] Meanwhile, an international research team, led by Dr. David Williams, chief of Hematology/Oncology at Boston Children’s Hospital, and Dr. Florian Eichler, who directs the Center for Rare Neurological Diseases at Massachusetts General Hospital, had developed a study protocol aimed at halting the progression of ALD using gene therapy. […] “There are two great advantages to gene therapy,” Dr. Williams says. “First, patients don’t have to wait to find a donor match. Second, because we use their own, gene-modified stem cells, there’s no risk of graft-versus-host-disease, and the patients do not require any immunosuppression drugs, which can have very significant, even fatal, side effects.”

• #31 Gene Therapy for ALD |

  https://adrenoleukodystrophy.info/treatment-options/gene-therapy-for-ald

  The primary efficacy endpoint of the Starbeam study was the absence of major functional disabilities (MFD) at 24 months post-transplant. […] These initial results suggest that gene therapy with Lenti-D for the treatment of cerebral ALD is at least as effective as conventional allogeneic transplantation. The absence of graft-versus-host disease suggests that it may be safer.

• #32 Treating ALD — The Stop ALD Foundation

  http://www.stopald.org/treating-ald

  There are currently only two available treatments for childhood cerebral ALD: Lorenzo’s oil and stem cell transplantation, using either umbilical cord stem cells or bone marrow stem cells. Both treatment approaches have shown promise, and been effective for some boys with ALD, but they also both have drawbacks. While research indicates that these treatments may be able to arrest the progress of the disease, neither can dramatically repair the damage done by ALD once it has already begun. To do that, a treatment would have to actually restore the lost myelin. […] Both Lorenzo’s oil and stem cell transplantation are considered treatments only for boys with childhood cerebral ALD; the options for treating men with adrenomyeloneuropathy (AMN), the adult form of the disease, are more limited. Currently, doctors will not perform stem cell transplantation on adults with the disease, generally because the risks of the treatment are considered to outweigh the potential benefits. But as transplantation technology improves and becomes safer, it is possible that stem cell transplantation will be available for men with AMN.

• #33 What is ALD? (Adrenoleukodystrophy Explained) – ALD Alliance

  https://www.aldalliance.org/ald-support.html

  For men with adrenolmyeloneuropathy methods of care consist of rehabilitation therapy, symptomatic medications for pain and stiffness, creating a diet and exercise regimen for ideal health. There are also clinical trials for developing medications that may be useful. […] The FDA approved bluebird bios gene therapy treatment for childhood cerebral ALD on September 16, 2022. Gene therapy is a treatment option for children with cerebral ALD that offers an alternative to allogenic hematopoietic stem cell transplant, eliminating the need for a bone marrow match. […] 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.

• #34 Dietary treatment for X-linked adrenoleukodystrophy: Is “Lorenzo’s oil” useful? | Endocrinología y Nutrición (English Edition)

  https://www.elsevier.es/en-revista-endocrinologia-nutricion-412-articulo-dietary-treatment-for-x-linked-adrenoleukodystrophy-S2173509313000020

  Various reports suggest that the administration of GTO/GTE to asymptomatic patients may prevent the occurrence of neurological symptoms, although further studies are needed. […] It is not recommended either in children under one year of age, because it may decrease the levels of essential fatty acids, particularly of docosahexaenoic acid. […] No benefit has been demonstrated in AMN, although if treatment has been started and is well tolerated, it may be continued. […] Once neurological involvement has occurred, GTO/GET is ineffective in preventing disease progression or achieving symptom remission. […] In this situation, the only treatment that could currently be effective (provided a compatible donor exists) is HSCT in the phase of early cerebral disease, although this does not correct an existing adrenal insufficiency.

• #35 Clinical Trials | ALD Connect

  https://aldconnect.org/clinical-trials-and-research/clinical-trials/

  Clinical trials are research studies designed to evaluate the safety, efficacy, and potential benefits of new treatments, drugs, or therapies in human participants. For adrenoleukodystrophy (ALD), clinical trials are crucial in advancing our understanding of the disease and developing effective treatments. These trials may involve gene therapy, medications, or other interventions aimed at slowing disease progression, improving symptoms, or correcting the underlying genetic mutations. Participants in ALD clinical trials contribute to scientific research that could lead to new therapies, offering hope for better management of the disease and improving the quality of life for those affected. […] Participation in clinical trials for ALD is not only a step toward potentially accessing new treatments but also a vital contribution to the broader ALD community. When individuals with ALD participate in trials, they provide researchers with critical data that helps to deepen the understanding of the disease, its progression, and how it responds to different interventions. This collective knowledge accelerates the development of new therapies, which can benefit everyone in the ALD community.

• #36 Clinical Trials | ALD Connect

  https://aldconnect.org/clinical-trials-and-research/clinical-trials/

  Additionally, clinical trial participation helps to identify which treatments are most effective and safe, paving the way for approval by regulatory bodies and wider availability. For families affected by ALD, participating in clinical trials is a way to be actively involved in the fight against the disease, offering hope not just for their own loved ones, but for all those who may be impacted by ALD in the future. […] A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adults Male Subjects with Cerebral Adrenoleukodystrophy. […] This is a prospective, non-therapeutic protocol designed to create and maintain a registry of participants with adrenoleukodystrophy (ALD) and known/presumed carriers of ALD. […] The primary objectives of this study are 1) to assess the prevalence of symptomatic courses in females with X-ALD and 2) to determine the impact of AMN symptoms on the quality of life of affected women in various areas (including everyday life, work, social network, sleep quality, sexuality, mood).

• #37 Clinical Trials | ALD Connect

  https://aldconnect.org/clinical-trials-and-research/clinical-trials/

  A randomized controlled first-in-human Phase 1/2 study to assess the safety and explore the efficacy of SBT101, an investigational gene therapy, over the course of 2 years in men with AMN. […] The investigators recently observed that up to 25% of women with X-linked adrenoleukodystrophy (ALD) have moderate to severe Restless Leg Syndrome (RLS). In this study, the investigators aim to estimate the prevalence of RLS among women with ALD and to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD. […] This trial will evaluate the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of CALD. A subject’s blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

• #38 Clinical Trials | ALD Connect

  https://aldconnect.org/clinical-trials-and-research/clinical-trials/

  Considering participation in a clinical trial for ALD or AMN is a significant decision that involves weighing potential benefits and risks. Clinical trials offer access to cutting-edge therapies and medical care that might not be available outside the research setting, providing hope for slowing disease progression or managing symptoms. Participation also plays a crucial role in advancing scientific knowledge, contributing to the development of treatments that could benefit the entire ALD community.

• #39 Adrenoleukodystrophy | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/adrenoleukodystrophy

  Currently, there is no complete cure for ALD, but there are treatments that significantly change the course of this disease. The following treatments are available: […] Stem cell transplant may stop or slow the progression of CALD if it is done when neurological signs first appear on a specialized image of the brain called an MRI. […] Gene therapy offers an alternative to stem cell transplant. Elivaldogene autotemcel (brand name: Skysona) is a one-time, ex vivo gene therapy that slows the progression of neurologic dysfunction. […] Doctors may prescribe medications to help relieve symptoms such as stiffness and seizures. […] Physical therapy may help relieve muscle spasms and reduce muscle rigidity. […] Many children with ALD develop adrenal insufficiency, which can be effectively treated with steroids. Adrenal insufficiency can be life threatening without treatment.

• #40 Adrenoleukodystrophy | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/adrenoleukodystrophy

  Targeted treatment of CALD has the best outcome when performed on an individual before symptoms are clinically visible. […] The gene therapy recently approved by the U.S. Food and Drug Administration (FDA) noted above offers an alternative treatment. It uses a child’s own stem cells, so it doesn’t require a match in the registry. […] In recent clinical trials, gene therapy has shown promising results in stabilizing the progression of the disease in boys with early-stage CALD. However, additional research is necessary to assess its long-term effectiveness and safety.

• #41 Khymir’s Story: Gene Therapy to Treat Cerebral Adrenoleukodystrophy | Children’s Hospital of Philadelphia

  https://www.chop.edu/stories/khymir-s-story-gene-therapy-treat-cerebral-adrenoleukodystrophy

  Khymir is a 4-year-old boy who was found to have adrenoleukodystrophy (ALD) through Pennsylvanias newborn screening. […] Recently became the first patient at CHOP to receive a groundbreaking gene therapy treatment. […] Fortunately, a gene therapy recently approved by the U.S. Food and Drug Administration (FDA) offers an alternative treatment. Elivaldogene autotemcel (brand name: Skysona) is a one-time, ex vivo gene therapy that slows the progression of neurologic dysfunction. […] In September 2023, 4-year-old Khymir became the first patient at CHOP to receive gene therapy for CALD. […] Dr. Adang is hopeful that halting CALD before its effects take hold will put Khymir and other kids like him on a path to a normal life. […] Newborn screening, standardized monitoring programs, and gene therapy are going to save lives. […] As long as you can find children pre-symptomatically, gene therapy has the potential to be transformative, and our children can live long, healthy lives.

• #42 Adrenoleukodystrophy (ALD) | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/adrenoleukodystrophy/

  Adrenal insufficiency can be treated by giving replacement hormones (which are essential for life). […] Cerebral ALD (cALD) can be effectively treated if it is detected at a very early stage, using bone marrow transplant (BMT, also called haematopoietic stem cell transplant (HSCT)). There is also a gene therapy transplant available in some countries (not currently the UK) that can treat early stages of cALD. […] If ALD is diagnosed, careful evaluation will be made to see if cALD has already developed. If it has not, ongoing regular check-ups including with regular MRI brain scans will be undertaken to look out for early signs of cALD. […] For boys who already have advanced stages of cALD when the diagnosis is first made, BMT/HSCT and gene therapy will not be suitable. In that situation, high-quality symptom care management will be important to address all the problems that ALD can cause. […] There is a lot of ongoing research exploring new potential treatments for the different aspects of ALD.

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