Finding new uses for old drugs – could calcium channel blockers be used in MND?

Our Advancing Treatments Awards are funding the development of promising treatment approaches as they move toward clinical testing. One of three projects we are funding this year is spearheaded by Professor Kevin Talbot of the University of Oxford. Professor Talbot is exploring whether calcium channel blockers – drugs normally used to treat high blood pressure – could find a second life as a treatment for MND.

Developing brand new treatments is a slow process. This is for good reason – when testing new compounds, which science has less knowledge of, researchers must make sure they are both effective and safe. But, people living with MND do not have time to wait. Exploring existing drugs that we already know are safe is a way to speed up this process.

In previous work, Professor Talbot’s team identified that one problem facing motor neurons affected by MND is cellular damage caused by oxidative stress.

During oxidative stress, unstable molecules called reactive oxygen species run amok throughout cells. Professor Talbot assembled a library of already-approved treatments and conducted a screen in mouse cells that had been modified to act like human cells affected by MND. A screen is essentially a massive game of Battleships in which successful hits represent existing treatments that reduced oxidative stress in the mouse cells.

One treatment that stood out is called nisoldipine, a calcium channel blocker that treats high blood pressure. Nisoldipine proved especially effective at reducing oxidative stress and helping cells survive longer.

In this new study that we are funding, Professor Talbot’s team will test a series of calcium channel blockers in cellular models of MND. This will determine whether calcium channel blockers are able to repair or reduce the cellular damage caused by MND. They will then undertake a deep molecular analysis to understand exactly how the calcium channel blockers exert any protective effects. Finally, the team will explore whether any effects are maintained in animal models of MND – the final step before human clinical trials.

Why is this research important?

The calcium channel blockers that Professor Talbot is testing are already in clinical use and their safety has been established. If the compounds have beneficial effects on motor neurons, then they would be prioritised for clinical study through studies like EXPERTS-ALS and MND-SMART, both of which we support. We would then be able to assess these treatments more quickly than those without proven safety data