The University at Albany team has developed a compound designed to reduce toxic CAG repeats that underlie 50–70 neurodegenerative diseases, including Huntington's. They received $50,000 from SUNY to advance development and have created 40 compound variants to solve solubility and safety issues. Current formulations dissolve only in solvents unsafe for patients, so further optimization and years of testing are needed before clinical trials. The project is supported by a mix of charity, federal and state funding and will rely on international patient networks for trials.
UAlbany Compound Could Treat Huntington’s and Dozens of Related Neurodegenerative Diseases
Scientists Hannah Shorrock and John Cleary look at a screen on the Xenium Analyzer in the Next Generation Transcriptomic Facility at the University at Albany on Tuesday in Albany. The machine takes tiny slices of tissue and visualizes RNA at a cellular level. (Lori Van Buren/Times Union)
Researchers at the University at Albany have developed a promising compound intended to reduce harmful CAG repeats — the genetic fault that drives 50 to 70 degenerative neurological diseases, including Huntington's disease. The team has received a $50,000 award from the State University of New York to advance the compound toward preclinical development and eventual clinical trials.
How the approach works
Many related disorders are caused by an expanded CAG repeat in a gene. That repeated sequence produces defective proteins; the longer the repeat, the earlier and more rapidly symptoms progress, leading to loss of speech, mobility and fine motor control, and ultimately breathing and swallowing difficulties. The Albany researchers' compound is designed to reduce production of the CAG-containing RNA so less toxic protein is made.
Progress and challenges
The team, led by researchers John Cleary and Hannah Shorrock, already has a compound that demonstrates the desired effect in laboratory studies. However, formulation and safety hurdles remain. The molecule is poorly soluble in liquids that would be safe for long-term human dosing: it dissolves in ethanol and in dimethyl sulfoxide (DMSO), but those solvents are unsuitable for patient use. In animal tests, the DMSO formulation caused mice to stop gaining weight, a concerning toxicity signal.
To overcome these issues the researchers have synthesized 40 chemical variants to find a version with acceptable solubility and safety for pharmaceutical use. The SUNY Technology Accelerator Fund award will help them identify the best candidate and advance it toward clinical testing. Even with progress, human trials are likely years away.
Funding, collaboration and scope
The project grew from a postdoctoral fellowship supported by the National Ataxia Foundation and philanthropic donations, and has since attracted funding from the National Institutes of Health, New York State and SUNY. Shorrock and Cleary emphasize the need for an international patient network to recruit enough participants for trials, because each individual disorder is rare. The team itself is international: Cleary is Canadian and Shorrock is British, and they say their work will build both research and economic benefits for the U.S.
"To knock them off one at a time, you're talking hundreds of years," said John Cleary. "We're pursuing overlapping therapies that could help many patients at once."
Outlook
If the team finds a formulation that is safe and effective, the same compound could potentially be adapted to treat the entire group of CAG repeat disorders. That would offer a rare opportunity to address dozens of debilitating diseases with a shared molecular therapy, but substantial development, testing and regulatory work remains.
