A research team led by the University of California, Irvine, has linked the mutation that causes Huntington’s disease to developmental deficits in oligodendrocyte cells in the brain that are caused by changes in metabolism. They found that high doses of thiamine and biotin can restore normal processes.
OL cells generate the insulating coating around neurons, called myelin. The study, published online in the journal Nature Communications, provides a detailed insight into the whole process of how these changes in genes that regulate cell metabolism impair the development of OL, as well as the therapeutic value of treating HD with high doses of thiamine and biotin. . Thiamin and biotin are B vitamins and are involved in a wide range of metabolic processes that help maintain a healthy nervous system.
Our findings validate that the HD-causing mutation leads to maturation deficits in myelin-producing cells and show that treatment with high doses of thiamine and biotin restores the normal function of these cells.”
Leslie Thompson, Ph.D., co-author and Donald Bren Professor and chancellor in the departments of psychiatry and human behavior and biological chemistry in the UCI School of Medicine, and neurobiology and behavior in the School of Biological Sciences.
Using advanced modeling methods, researchers confirmed that in mouse and human HD brain tissue, the maturation state of OL cells and their precursors is arrested at mid-development, impairing myelin production which is critical for neural health and function. They found that high doses of thiamine and biotin were connected to a significant rescue of gene expression changes in OL cells.
“The mechanisms of HD OL pathology and how these changes occur are not fully understood,” said Ryan Lim, Ph.D., study co-author and MIND Research Unit project scientist. “Our next steps will be to longitudinally follow the effects of thiamine and biotin treatment in HD mice, so that we can further elucidate these molecular and cellular processes, evaluate the efficacy of this therapeutic approach, and identify other targets that may benefit HD patients.”
Team members also included co-corresponding author Dr. James E. Goldman, Professor of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons; and co-first authors Jie Wu, project scientist at the UCI School of Medicine; and Osama Al Dalahmah, assistant professor of pathology and cell biology, Columbia University College of Physicians and Surgeons; as well as faculty and graduate students at the Massachusetts Institute of Technology; and the University of the City of New York.
Source:
University of California – Irvine
Journal reference:
Lim, RG, et al. (2022) Huntington’s disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation. Communications of nature. doi.org/10.1038/s41467-022-35388-x.