Active research into leukodystrophies is happening worldwide (including Australia). New and experimental therapies are constantly being tested and tried to overcome the effects of the various causes of leukodystrophy and to either reduce the symptoms, slow the progression, or halt the progress of the disease altogether. Some of the leukodystrophies respond to relatively simple therapies. For example, Cerebrotendinous Xanthomatosis – patients can be helped by taking a simple oral medication to normalise cholesterol metabolism. The fat which accumulates in the blood of patients with Refsum’s disease (phytanic acid), for example, can be cleared by the implementation of a diet which restricts the intake of this fat in the diet. This can be beneficial for muscle strength and nerve function, and can arrest the deterioration of vision and hearing. International clinical trials on the effects of Lorenzo’s Oil therapy on Adrenoleukodystrophy are still in progress. The studies mostly involve patients who carry the abnormal gene but have not yet developed the disease. It has already been established that this treatment can reduce the levels of the very long chain fats in the blood (these substances accumulate in the tissues and blood of patients and are believed to contribute to the disease), but as yet it is not known whether damage to the brain can be prevented.
Another form of therapy which is showing promise is the partial replacement of mutated, inactive protein with active protein. This can be achieved by bone marrow transplantation. Stem cells derived from the transplant, which contain normal active protein, are able to handle the substance, which the patient’s body is unable to cope with. This form of therapy has already been used to treat some of the leukodystrophies, such as Adrenoleukodystrophy or Metachromatic Leukodystrophy. However, matched donors must be available and the procedure carries a risk, and there is still a question as to the extent to which the new cells can enter the brain – the organ most affected by leukodystrophies. Also, it is preferable that the procedure be used before possible irreversible damage to the brain occurs. An alternative approach is enzyme replacement therapy, in which the patient is administered the active protein obtained from some other source.
Perhaps the most exciting development is the replacement of the gene itself. In March 1996, in New Zealand, the world’s first human gene therapy trials for a neurological disease were carried out on two children with Canavan disease. Further trials involving more children have since been conducted and research into novel gene replacement therapies for other leukodystrophies is currently ongoing.
Early diagnosis of leukodystrophies is key for any successful therapy as many symptoms are unfortunately irreversible. Research in recent years has significantly improved the diagnosis of leukodystrophies and many new therapies are currently under development. To learn more about which clinical studies are happening for Leukodystrophy disease go to www.clinicaltrials.gov.
“Invitation to participate in research: Natural history study of Pelizaeus-Merzbacher Disease (PMD)
(HREC/61136/RCHM-2019) The Murdoch Children’s Research Institute, in collaboration with the Children’s Hospital of Philadelphia is studying the natural history of PMD in order to understand how PMD progresses over time in individuals of all ages. Understanding the natural progression of the disease is needed in order to accurately evaluate the effect of novel therapies. This study will involve the collection of information from existing medical records of individuals with PMD with consent from the individual, parent or guardian. The study does not require you or your child to do anything other than provide consent to access medical records.
If you or your child have been diagnosed with PMD and would like to participate or find out more about the study, please provide your details and preferred contact method to the study coordinator Eloise Uebergang at firstname.lastname@example.org
Passage Bio, a genetic medicines company developing AAV-delivered gene therapies for the treatment of rare monogenic central nervous system diseases, today announced that its third clinical trial program will be for infantile Krabbe disease, an inherited disease that causes progressive damage to the nervous system.
MASSIMO’S MISSION PROGRAM AND THE LEUKODYSTROPHY CLINIC
LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
Garvin Institute of Medical Research
Global Leukodystrophy Initiative are a global consortium of scientists, patient advocates, physicians, and families committed to improving the lives of individuals affected by white matter disorders
ClinicalTrials.gov is a database of privately and publicly funding clinical studies conducted around the world
Centre for White Matter Disease at VU University in Amsterdam where you will find neurologists Prof Marjo van der Knaap and Dr Nicole Wolf, world expert on hypomyelinating Leukodystrophies, of which PMD is one of the most common
ORPHANET The official journal of Orphanet, the portal for rare diseases and orphan drugs