- On the research front, Cure SRD5A3 is actively funding drug repurposing and gene therapy programs.
- On the drug repurposing side, we are working with the Canadian biotechnology company Modelis to generate genetic models for SRD5A3-CDG in worms and zebrafish. SRD5A3-deficient worms exhibit a slow motility phenotype compared to wild-type worms. These worms are currently being used to evaluate whether a library of drugs can improve their movement, which could translate to patient benefit. Modelis is also generating SRD5A3-deficient zebrafish.
- On the gene therapy side, Cure SRD5A3 is working with Dr. Steven Gray’s lab at the University of Texas Southwestern Medical Center in Dallas, Texas, to develop and test adeno-associated virus (AAV) gene therapy as a potential treatment SRD5A3-CDG. On that front, the gene therapy has been designed and is currently being tested for safety in normal mice. It will also soon be in SRD5A3-deficient mice (originally generated by Dr. Vincent Cantagrel). A similar SRD5A3-deficient mouse model will also soon be available to the broader research community through Jackson Laboratories.
- Beyond the work on drug repurposing and gene therapy, internal research efforts led by Cure SRD5A3 Research Program Director, Omid Karkouti, are being used to generate patient-derived cell-based models for SRD5A3-CDG, and assays to evaluate their effects in cells, animal models, and patient samples.
- Beyond evaluating potentially effective therapies for SRD5A3-CDG, one of the important questions Cure SRD5A3 wishes to answer is a mechanistic understanding of whether disease is primarily caused by polyprenol accumulation or dolichol deficiency.