Peroxisome Biogenesis Disorder (PBD) Clinical Trial
Official title:
A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders.
The PBD are a rare group of inherited disorders due to the failure to form functional cellular peroxisomes. Most patients have progressive hearing and visual loss, leading to deafness and blindness, as well as neurological deterioration. There are no therapies for this disorder. A misfolded protein with residual function, PEX1-Gly843Asp, represents one third of all mutant alleles. Using patient cell lines with this mutation, we reported the recovery of peroxisome functions by treatment with Betaine, acting as a nonspecific chemical chaperone for the misfolded PEX1 protein. Betaine, or trimethylglycine, is a Health Canada and FDA approved orphan drug for the treatment of homocystinuria and is used by us safely and regularly in genetic medicine. We will perform a 6 month pilot study with 12 patients to test the hypothesis that Betaine, at recommended doses, can recover peroxisome biochemical functions in blood.
Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty
assembly of peroxisomes, structures located inside cells that regulate levels of important
fats and lipids in the body. When there is faulty peroxisome assembly, as in PBD, these
important fats and lipids either accumulate or are not made. These changes result in
abnormalities of organ formation that a child is born with, such as changes in bone, brain
and eye formation. There is no specific treatment for these disorders, and management is
supportive. In order to complement existing supportive therapies, physicians and researchers
are still actively looking for new treatments acting on the root cause of PBD: the
peroxisome function. To identify drugs that help recover peroxisome function a group of
scientists have developed a test to be used in laboratories, aiming at reviewing the
activity of the large number of potential treatments.
Using this test, they have uncovered that Betaine can improve the function of the
peroxisome, when the defect is caused by a PEX1-Gly843Asp mutation, and as such may improve
the overall health of child suffering from PBD.
Betaine is a medication already available as a powder for oral solution, for another rare
disease. It is approved in many countries, including Health Canada for Canada and the Food
and Drug Administration for the USA. Paediatric genetic physicians are used to prescribing
this medication and know it well.
At the current stage of scientific knowledge, it is a critical next step to evaluate the
benefit of betaine in children having a PBD due to a PEX1-Gly843Asp mutation, to ensure that
the medication is safe and to measure the level of improvement of the function of the
peroxisome.
Thus, the principal objective of the study is to determine the improvement in the key
peroxisome functions (plasma very long chain fatty acid profiles red cell plasmalogen
levels, plasma pipecolic acid levels and plasma bile acid profiles). Another objective is to
measure the growth of your child and his / her development.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment