On Tuesday of this week, Francis S. Collins, MD, PhD, announced he would step down from his role as Director of the NIH by the end of this year. The esteemed physician-geneticist is credited with the discovery of genes associated with numerous diseases, and was a part of the team that discovered the gene responsible for Huntington’s disease in 1993. When he was appointed to the role by President Obama in 2009, Dr. Collins was leading the international Human Genome Project at the National Human Genome Research Institute. As he ends his over 12-year tenure under three presidential administrations with intentions to return to the lab, we celebrate Dr. Collins’ accomplishments advancing genetic and brain disease research initiatives in addition to his achievements furthering research for cancer treatments, understanding of opioid misuse and addiction, and numerous efforts to further knowledge of the effects and measures to prevent the spread of COVID-19. Dr. Collins has been a tremendous friend to the HD Community; we owe him a debt of gratitude and wish him the best in his future endeavors!
Potential Therapeutic Target for HD: Thiamine
There are diverse research efforts currently underway to investigate possible gene-silencing therapies for HD, but exploration of other molecular mechanisms through which the toxic effects of mutant huntingtin protein (mHTT) come to be may unveil new targets for treatment of HD. A research group from the Center for Molecular Biology at the University of Madrid have identified a thiamine transporter gene, ThTr2, as a potential therapeutic target for HD. This gene has previously been linked to a neurometabolic brain disorder called biotin-thiamine-responsive basal-ganglia disorder (BTBGD). Similarly irregular levels of ThTr2 proteins in individuals with BTBGD and persons with HD have been linked to decreased striatal concentrations of metabolically active thiamine, indicating issues with uptake of thiamine. Individuals with BTBGD have had positive clinical outcomes from treatment with a combination of thiamine and biotin, and researchers are wondering if the same combination may lead to improvements in HD.
In a study recently published in the journal Science Translational Medicine, administration of high doses of thiamine and biotin led to reduced brain-cell damage in the striata of HD mice. The doses administered were much higher than could be achieved through diet alone, and vitamin excess from imbalanced supplementation can have toxic effects in humans. These early findings will be further explored in a pilot clinical trial in participants with HD to determine whether the doses required for positive therapeutic outcomes are safe and tolerable for people. Read more about the study here.
Help 4 HD: The Heart in HD
Help 4 HD podcast host, Lauren Holder, was recently joined by Dr. Sophie St-Cyr, a biologist at the Children’s Hospital of Philadelphia, to discuss her research on cardiac symptoms in individuals affected by HD. Heart disease is the second cause of mortality from HD, and the disease has been linked to heart abnormalities like cardiac arrhythmia, smaller heart size, and impaired stress response. Dr. St-Styr studies how RNA might contribute to HD-related heart abnormalities, specifically RNA-binding proteins (RBPs) that determine how multiple proteins can be produced from the same gene. Her hypothesis is that an imbalance of RBPs responsible for development of heart tissue results in these changes. To learn more about Dr. St-Cyr’s research in mouse models of HD, listen to the full podcast episode here.