Overview

Betaine and Peroxisome Biogenesis Disorders

Status:
Completed
Trial end date:
2015-06-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
McGill University Health Center
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators:
Children's Hospital & Medical Center Omaha
Children's Hospital and Medical Center, Omaha, Nebraska
Treatments:
Betaine
Criteria
Inclusion Criteria:

- Males or females

- Any age

- Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two
peroxisomal enzyme parameters:

- Elevated plasma VLCFA (C26/22) > 0.02

- Elevated plasma branched chain pristanic acid > 0.3 μg/ml

- Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07

- PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum
disease (IRD)

- Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1
mutation that is predicted to be null

- Expected survival of at least 6 months

Exclusion Criteria:

- Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any
second PEX1 mutation that is predicted to be null

- Patient already treated with betaine