Failed Drug May Have New Life as Treatment for Rare Motor Neuron Disease

Rare Daily Staff

A team of international researchers have identified a failed drug first discovered in the 1980s as a potential new treatment for hereditary motor neuron disease, a rare and progressive condition that damages the nerves that control movement.

About 20 percent of the cases of inherited motor neuron disease are caused by mutations in a gene that codes for a protein called SOD1. When the SOD1 gene is mutated, the protein assembly process is incomplete and the SOD1 protein that is produced is structurally unstable leading to formation of protein clumps in the motor neurons that cause them to die.

In a study led by biochemists at the University of Liverpool and published in the journal Nature Communications, scientists show that the drug ebselen can correct many of the toxic characteristics of the protein that causes some cases of hereditary motor neuron disease. The Motor Neurone Disease Association funded the research.

Ebselen had originally been developed as a potential treatment for strokes but was abandoned during development because studies failed to show it was efficacious. It has been explored as a potential treatment for a variety of conditions including bipolar disorder and hearing loss.

The researchers found that ebselen can effectively restore several important steps in the SOD1 assembly process.

“This discovery has the potential to prevent the accumulation of SOD1 into the large aggregates we see within the motor neurons of effected individuals,” said Gareth Wright, an MND researcher at the University of Liverpool. “If we can stop that, we might be able to stop the neurons dying.”

The researchers said the next step is to test ebselen in settings more accurately resembling human neuronal cells and optimizing it so that it can become useful as a drug for motor neuron disease.

May 22, 2018
Photo: Gareth Wright, an MND researcher at the University of Liverpool