Repurposed FDA-approved drug could uncover potential treatment for rare genetic disorders microbiologystudy

In a new study, researchers at McMaster University have identified a potential treatment for Sandhoff and Tay-Sachs diseases—two rare, often fatal lysosomal storage disorders that cause progressive damage to nerve cells in the brain and spinal cord.

The team’s findings were published in the journal Human Molecular Genetics.

After years of investigating the diseases’ underlying mechanisms, the research team has identified an existing FDA-approved drug that could significantly improve quality of life for affected patients and their families.

“Sandhoff and Tay-Sachs are devastating diseases,” says Suleiman Igdoura, a professor of biology and pathology who has been researching these conditions for years. “They’re marked by progressive loss of motor functions—from sitting, standing, and swallowing to even breathing—as neurons in the nervous system die. Watching someone go through this is heartbreaking.”

Tay-Sachs disease, the more common of the two disorders, typically manifests within the first year of life, progressing quickly and often proving fatal within a few years. In rare cases, symptoms of Tay-Sachs and Sandhoff disease appear later in childhood or even in early adulthood, progressing more slowly and offering a longer—but still profoundly challenging—life course.

“Patients often require intensive hospital care as symptoms worsen, and our current treatment options are severely limited,” explains Igdoura. “But now, there’s hope.”

By studying late-onset cases, Igdoura and his team uncovered that these diseases begin in the spinal cord, where chronic stress on a cellular component called the endoplasmic reticulum triggers programmed cell death. Observing the decline in spinal cord neurons in late-onset patients provided crucial insights into how the disease progresses throughout the body.

This breakthrough led to the identification of a potential therapeutic compound: 4-phenylbutyric acid (4-PBA), an FDA-approved drug initially developed for another condition. Testing in a mouse model of the disease showed that 4-PBA significantly improved motor function, extended lifespan, and increased the number of healthy motor neurons.

As one of the few labs in the world studying Sandhoff and Tay-Sachs, Igdoura and his team are optimistic that this discovery could be transformative.

“We receive heartbreaking stories from families around the world affected by these diseases,” says Igdoura. “Offering an FDA-approved drug for off-label use could provide hope and improve both life expectancy and quality of life for these patients.”

Further research is underway to identify the optimal human dosage of 4-PBA.

The insights gained from studying Sandhoff and Tay-Sachs may also have broader implications, potentially informing research into other neurodegenerative diseases such as Alzheimer’s and ALS.

“There may be lessons here that apply to a range of neurodegenerative conditions,” Igdoura says.