The National Institute of Neurological Disorders and Stroke awarded the University of California, San Diego $236,115 on August 28, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to examine the impact of cobalamin C deficiency in human brain development.
The research investigates cobalamin C deficiency, one of the most common inborn errors of metabolism, which interrupts methionine remethylation and causes neonatal-onset encephalopathy, hypotonia, microcephaly, and neurodevelopmental delay in affected individuals. Current treatments are ineffective for neurological manifestations, and most patients experience severe developmental delays and intellectual disability despite early diagnosis and treatment. Principal investigator Dr. Huang, a clinical geneticist specializing in inherited metabolic disorders, will investigate the role of cobalamin C deficiency in human brain development using a human brain organoid model and develop a gene-editing approach to correct common mutations. The research program includes three aims: examining the timing and stage of differentiation blockage during oligodendrogenesis; exploring how disrupted methionine remethylation impacts the creatine synthesis pathway; and proposing an innovative intervention strategy.
Performance occurs in La Jolla, California. The period of performance runs through July 31, 2031.