New hope for rare genetic disorders: USFDA-Approved drug shows promise

New Delhi (The Uttam Hindu): A team of Canadian researchers has found an existing US Food and Drug Administration-approved drug that could significantly improve the quality of life for patients affected with Sandhoff and Tay-Sachs diseases -- two rare genetic disorders. Sandhoff and Tay-Sachs diseases cause progressive damage to nerve cells in the brain and spinal cord. There is currently no cure for both disorders. After years of investigating the diseases’ underlying mechanisms, the research at McMaster University identified a potential therapeutic compound: 4-phenylbutyric acid (4-PBA). 4-PBA is an FDA-approved drug that was initially developed for another condition.

Suleiman Igdoura, a professor of biology and pathology at the varsity stated that Sandhoff and Tay-Sachs “are devastating diseases that are marked by progressive loss of motor functions -- from sitting, standing, and swallowing to even breathing -- as neurons in the nervous system die”. In the study, published in the journal Human Molecular Genetics, the team tested 4-PBA in a mouse model of the disease. The results showed that 4-PBA significantly improved motor function, extended lifespan, and increased the number of healthy motor neurons. 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.” The team focussed on the late-onset of the rare diseases. They found that these originate in the spinal cord -- where chronic stress on a cellular component called the endoplasmic reticulum triggers programmed cell death. Igdoura said offering 4-PBA for “off-label use may provide hope and improve both life expectancy and quality of life for these patients.” He noted that the findings may have broader implications, potentially informing research into other neurodegenerative diseases such as Alzheimer’s and ALS.