Repurposing Diazepam as a new therapeutic approach for ALS

FightMND Drug Development Research Grant (DDG)

Repurposing - using an existing drug for new diseases - offers significant advantages in decreasing the development cost/time for treatments compared to discovering new medicines. This research will examine a known, widely prescribed drug for which extensive literature is already available. The drug directly targets an important disease mechanism in ALS, making this project highly promising. The main hallmark of MND is the production of faulty TDP-43 protein, occurring in 97% cases. Importantly, we know that this drug prevents the accumulation of faulty TDP-43 in cells. We will determine in this study if it is protective in two mouse models that represent genetic forms of MND and the much more common sporadic forms of disease. Rodents are commonly used disease models because they have similar genetics and brains to humans. The MND mice develop paralysis, impaired movement and muscle strength and motor neuron death. If the drug prevents these important features in MND mice, it will provide strong evidence of its potential for treating these characteristics of human MND. Thus, this study will reveal whether this drug has potential to be repurposed for MND. The drug would treat MND by reducing nerve overactivity and boosting GABA, a key neurotransmitter. Its mechanism is well understood since it has been FDA-approved for 60+ years, and over 27,500 studies supporting its effects. As the drug also clears the key hallmark of TDP-43, this suggests it has broad benefits for MND