Researchers have discovered a possible treatment for Sandhoff and Tay-Sachs diseases, which are two rare and often deadly lysosomal storage disorders that lead to progressive damage in the brain and spinal cord’s nerve cells. After many years of studying how these diseases operate, the research team has pinpointed an already approved drug by the FDA that could greatly enhance the quality of life for patients and their families.
A pioneering study conducted by researchers at McMaster University has revealed a potential treatment for Sandhoff and Tay-Sachs diseases, two uncommon and frequently life-threatening lysosomal storage disorders resulting in gradual nerve cell deterioration in the brain and spinal cord.
Following extensive research into the diseases’ fundamental processes, the team discovered an FDA-approved medication that could markedly improve the lives of those affected.
“Sandhoff and Tay-Sachs are truly tragic conditions,” states Suleiman Igdoura, a biology and pathology professor who has spent years researching these illnesses. “They are characterized by a gradual loss of motor abilities, affecting everything from sitting and standing to swallowing and even breathing as nerve cells in the nervous system fail. Witnessing this situation is heartbreaking.”
Tay-Sachs disease, which is more prevalent between the two disorders, usually appears within the first year of life, advancing rapidly and often resulting in death within a few years. Occasionally, symptoms of Tay-Sachs or Sandhoff disease may emerge later in childhood or early adulthood, progressing more slowly and offering a prolonged but still extremely difficult life journey.
“As symptoms deteriorate, patients frequently require intensive hospital care, and our existing treatment options are very limited,” notes Igdoura. “But now, there is a glimmer of hope.”
By examining late-onset cases, Igdoura and his associates found that these disorders initiate in the spinal cord, where ongoing stress to a cellular component known as the endoplasmic reticulum triggers a process of programmed cell death. Monitoring the loss of spinal cord neurons in late-onset patients provided vital information about how the disease spreads throughout the body.
This significant finding led to the discovery of a possible therapeutic agent: 4-phenylbutyric acid (4-PBA), a drug that has already received FDA approval for another health condition. Tests on a mouse model of the diseases indicated that 4-PBA greatly enhanced motor skills, prolonged lifespan, and increased the number of healthy motor neurons.
The team’s research results have now been published in the journal Human Molecular Genetics.
As one of the very few laboratories globally focused on Sandhoff and Tay-Sachs, Igdoura and his team are hopeful that this discovery might be game-changing.
“We receive very sad stories from families across the globe dealing with these diseases,” comments Igdoura. “Providing access to an FDA-approved drug for off-label use could instill hope and enhance both life expectancy and quality of life for these patients.”
Additional research is currently being conducted to determine the ideal human dosage for 4-PBA.
The knowledge gained from researching Sandhoff and Tay-Sachs could also have wider implications, potentially aiding research into other neurodegenerative conditions such as Alzheimer’s and ALS.
“There may be valuable lessons here that relate to a variety of neurodegenerative disorders,” concludes Igdoura.
