Doctors in the UK are to launch a world-first clinical trial to assess whether drugs already on the market can prevent multiple sclerosis (MS) from worsening over time and even reverse the disabilities it causes. The groundbreaking Octopus trial, so named because of its various arms, will allow researchers to investigate the potential benefits of several drugs at once, in the hope of identifying effective new treatments three times faster than if the medicines were trialled separately. Hundreds of patients sought for the trial will be randomly assigned to have either standard care for progressive MS or standard care plus one of three drugs that doctors hope will at least protect their neurons from the disease if not repair the damage done. “It’s the first multi-arm, multi-stage trial for progressive MS in the world,” said Jeremy Chataway, a professor of neurology at University College London, who will co-lead Octopus with Mahesh Parmar, a professor of medical statistics and epidemiology, also at UCL. “It’s a more efficient way to go. I want this to mean that we get effective treatments for progressive MS faster,” he said. The team hope to start recruiting patients for the trial, which is funded by the MS Society through its Stop MS appeal, later this year, provided the coronavirus crisis does not interfere with its plans. About 130,000 people in the UK live with MS. The condition arises when the immune system mistakenly attacks the fatty myelin sheaths that wrap around nerves in the brain and spinal cord. Without the lipid-rich coating, electrical signals travel more slowly along nerves, are disrupted or fail to get through at all. Most people with MS are diagnosed between the ages of 20 and 50. Among the earliest signs are tingling, numbness, a loss of balance and problems with vision, but because other conditions cause the same symptoms, it can take time to reach a definitive diagnosis. Many patients have relapsing MS at first, a form of the disease where symptoms come and go as nerves are damaged, repaired and damaged again. But about half have a progressive form of the condition in which nerve damage steadily accumulates and causes ever worsening disability. Patients may experience tremors, speech problems and muscle stiffness or spasms, and may need walking aids or a wheelchair. There are more than a dozen drugs on the market that treat relapsing MS. They tend to be anti-inflammatories that hamper the immune system’s misguided attack on the central nervous system. But doctors have far fewer options to help the tens of thousands of patients whose MS has become progressive. “Whether we can protect the nerve cells and regenerate myelin, that is where the battleground is now,” said Chataway. The Octopus trial is intended to accelerate the search for drugs to treat progressive MS by comparing three against the same control group and rolling trial phases together. The design means that as soon as a drug shows any benefit, more patients can be recruited to gather further data on its efficacy and any side-effects. Patients who volunteer for the trial will have a brain scan after 18 months to see whether the drug they are receiving have slowed down the brain shrinkage that MS causes. If a drug is having no effect, it can be replaced with another medicine and the trial continues. Other tests may look at electrophysiology to see how well signals move around the central nervous system, biological markers that reveal when nerve damage is being repaired and levels of disability. Doctors are expected to decide which drugs form part of the trial this summer. “This trial could revolutionise treatment for people with progressive MS. They could stop worrying about the condition getting worse,” said Dr Emma Gray, the MS Society’s assistant director of research. A major trial is already under way to see whether the anti-cholesterol drug simvastatin protects against nerve damage in progressive MS. Doctors also have hopes for the diabetes drug metformin, which has been shown to repair damaged myelin in animals, probably by stimulating stem cells to repair the ailing nerve cells. Doctors showed last year that the cancer drug bexarotene can repair nerves in humans, an important proof of principle, but its side-effects are too severe to use as an MS treatment. “Ultimately, MS will be treated with a combination of drugs,” said Gray. “You’ll have immunomodulatory drugs and anti-inflammatory drugs that stop the immune attacks, and they will be combined with treatments that can protect nerves from damage, and treatments that can repair the damaged myelin. That should stop MS.”