Substrate reduction therapy has gained attention as a potential treatment for various genetic disorders, including Glutaric Aciduria Type 1 (GA1). Both GA1 and PDE are part of the same metabolic pathway involving the degradation of lysine, making substrate reduction therapy a relevant approach to both disorders. Video can be found here.
Dr. Sander Houten’s Expertise in Inborn Errors of Metabolism
Dr. Sander Houten, a Clinical Biochemical Geneticist with over two decades of experience, has focused his research on inborn errors of metabolism. He discovered that mevalonate kinase deficiency causes hyper-IgD syndrome and conducted studies to understand the transcriptional control of metabolism in various models.
Substrate Reduction Therapy for GA1
Glutaric Aciduria Type 1 (GA1) is a rare autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH), leading to the accumulation of neurotoxic glutaric acid and 3-hydroxyglutaric acid. Dr. Houten’s presentation on substrate reduction therapy for GA1 outlined the potential of inhibiting 2-Aminoadipic semialdehyde synthase (AASS), which catalyzes the first step in the lysine degradation pathway. By reducing substrate accumulation, this therapy could offer a safer and more effective treatment for GA1 and PDE patients.
Connecting GA1 and PDE
Pyridoxine-Dependent Epilepsy (PDE) is also part of the lysine degradation pathway, involving similar metabolic processes. Given the common pathway, substrate reduction therapy could hold promise for treating both GA1 and PDE. The focus on reducing harmful substrates in the body could lead to more effective management of these disorders, improving patient outcomes and quality of life.
Conclusion
Dr. Houten’s work on substrate reduction therapy for GA1 and its implications for related pathways such as PDE offers a glimpse into the future of treatment for rare genetic disorders. By advancing research in this area, we can continue to develop innovative therapeutic approaches that address the root causes of these conditions and pave the way for better patient care and outcomes.
