Early results from a clinical trial suggest that a common diabetes drug taken with an antihistamine can partially repair damage in the nervous system that drives disability in multiple sclerosis.
While the effect was too small for patients to notice a benefit after six months, tests did reveal improvements in nerve function, raising hopes that damage to the protective coatings around nerve fibres might be reversed with drugs.
“I feel like we’re at this precipice of a new class of therapies for MS and that’s why this is exciting,” said Dr Nick Cunniffe, a neurologist at the University of Cambridge who led the CCMR Two trial.
Nearly 3 million people worldwide live with multiple sclerosis and there are more than 150,000 patients in the UK. Most are diagnosed in their 30s and 40s. It is the most common neurological condition in young adults.
The disease arises when the immune system attacks protective fatty coatings around nerves in the brain and spinal cord. The loss of these myelin sheaths slows electrical signals passing along the nerves or stops them getting through entirely.
The first symptoms tend to be tingling, numbness, a loss of balance and vision problems, but because other illnesses cause similar ailments, a definitive diagnosis can take time.
Many patients start with relapsing MS, where symptoms come and go as the myelin sheaths around their nerves are damaged, repaired and damaged again. Others have a progressive form in which the body can no longer repair the damaged myelin and the nerve cells steadily die off. This drives progressive disability and symptoms such as tremors, speech problems, muscle stiffness and spasms. In time patients may need a walking aid or wheelchair.
In the past decade, scientists found that an antihistamine called clemastine had the potential to reinvigorate the body’s myelin repair mechanisms and potentially prevent progressive nerve damage. But its potency is unclear. The ReBuild trial at the University of California, San Francisco, found that while clemastine improved nerve function, the effect was very small.
The CCMR Two trial, funded by the MS Society, built on further research that showed metformin, a diabetes drug, might enhance the effect of clemastine.
The Cambridge trial recruited 70 people with relapsing MS. Half took clemastine and metformin and half received a placebo for six months. To assess the effect on nerves, the researchers measured how fast electrical signals zipped between the eyes and the brain. This was slower than normal in patients on the trial because of damage to the myelin and inflammation around the optical nerve.
While the drugs appeared to boost nerve function, there was no improvement in the patients’ vision or disability. Electrical signals travelled faster in people on the drugs than on the placebo, but only by 1.3 milliseconds.
“It’s smaller than we were hoping for,” said Cunniffe, who described the work at the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona on Friday.
“My conclusion is that the drugs have a biological effect to promote remyelination, but we need to be clear that people do not feel better on these drugs over six months,” Cuniffe said.
Emma Gray, director of research at the MS Society, said: “These are really positive proof of concept results and we’d like to see them followed up.
“We would not expect them to have a clinical benefit after only six months. It will take longer for this to be seen.”
The researchers stressed that people should not attempt to get hold of the drugs outside of a clinical trial as they were still being assessed. In the Cambridge trial, many patients experienced fatigue from clemastine and diarrhea from metformin. Drugs that remyelinate nerves would not regenerate nerves that have already died.
Jonah Chan, a professor of neurology at the University of California, San Francisco, who worked on the ReBuild trial, said finding drugs to remyelinate nerves was crucial.
“I’m more convinced than ever that remyelination is the critical path to preventing permanent disability in MS. It is also the only immediate hope for restoring function, albeit people have to be realistic about in what contexts it can restore function,” he said.
“We need to use everything we have learned over the last decade of hard work and struggle to pursue scientifically, experimentally validated compounds from the lab to see if they really work in people. We need to be inspired by optimism but comfortable with learning from setbacks.”