Potential treatment for rare degenerative disease discovered

Potential treatment for rare degenerative disease discovered
© iStock/RossHelen

Researchers have discovered a potential treatment for the rare Wolfram Syndrome – a degenerative disease.

Researchers from Yale have uncovered the mechanism behind a rare and lethal disease called Wolfram Syndrome along with a potential treatment. Wolfman’s Diseases is a progressive, degenerative disease that affects about one in 500,000 people worldwide and is characterised by diabetes in childhood, followed by psychiatric symptoms, loss of vision, deafness, and incontinence – with most patients dying in their 30s.

The research has been published in the journal Proceedings of the National Academy of Sciences.

Understanding Wolfram Syndrome

The team, led by pharmacology professor Barbara Ehrlich, have proposed a potential treatment involving two existing drugs and

have confirmed in their study that calcium inside cells play a key role in the disease. The research shows that when the protein Wolframin is lost in cells in the pancreas, “calcium signalling goes awry,” Ehrlich said. This, the team found, results in reduced cell viability and lower insulin secretion, which, in turn, triggers the debilitating symptoms of the disease.

By testing a number of compounds for their effectiveness in restoring calcium signalling and improving cell functions, the team found the two drugs that worked – ibudilast and a calpain inhibitor.

The role of calcium

Calcium supports a variety of critical biological functions, said Ehrlich, and the team have scrutinised calcium that is found in solutions inside cells and bodily fluids, which is necessary for muscle contraction, nerve function, and insulin secretion.

“Calcium is a signalling molecule,” Ehrlich said. “It will signal, for instance, when insulin should be secreted.”

Tom Fischer, a medical student from Germany working in Ehrlich’s lab, said: “The first step was to better understand what the protein Wolframin does. In our cell model that is lacking Wolframin, we measured intracellular calcium and found that calcium signalling as well as calcium-dependent cell functions, particularly insulin secretion and cell viability, were disrupted.”

The team will begin a study in mouse models within six months, with potential to move to human trials if successful.  

Although Wolfram Syndrome is a rare disease caused by genetic mutations in a single gene, it is tied to a number of other diseases that could be viable targets for this treatment, including diabetes and bipolar disorder, the researchers said.

Ehrlich said: “Some people with bipolar disorder also have mutations in Wolframin. This might be one of the first genetically identified mood disorders, and we will definitely be exploring this more.”


Please enter your comment!
Please enter your name here