A groundbreaking clinical trial is offering new hope to patients with progressive multiple sclerosis, a devastating neurological condition that affects more than 75,000 people in the UK and has virtually no available treatments. The world-first Octopus trial, led by Professor Jeremy Chataway at the National Hospital for Neurology and Neurosurgery in London, represents an innovative approach to drug development using adaptive trial methodology.
Revolutionary Trial Design
The Octopus trial employs a multi-armed, multi-staged design that allows researchers to test several potential treatments simultaneously while maintaining the ability to add new medications as they become available. This adaptive approach, previously successful in cancer and COVID-19 research, offers significant advantages over traditional clinical trial methods.
"We put patients on two already available drugs and a placebo. They will have an MRI scan and at that point they will carry on recruiting for the trial," explained Professor Chataway. "After about a year, they will look at an MRI scan of their brain and decide whether to carry on with all the medications or whether to drop some. That is the multi-stage. The multi-arm is the point at which they can then look at adding in new medications."
Targeting Disease Mechanisms
The trial is currently evaluating two repurposed medications: metformin, commonly used in diabetes treatment, and lipoic acid, an anti-inflammatory compound. In multiple sclerosis, the protective myelin coating around nerve fibers is progressively stripped away, leading to neurological deterioration. Metformin may help promote nerve regeneration, while lipoic acid aims to control the inflammatory processes that drive disease progression.
Addressing Critical Unmet Need
Progressive MS represents one of the most challenging forms of the disease, characterized by gradual worsening of symptoms without periods of remission. Brad Johnson, a 38-year-old management consultant diagnosed with primary progressive MS eight years ago, exemplifies the devastating impact of this condition.
"I get very tired, I have to plan when I'm going, and it takes quite a lot, actually, to get me out the house, so it has to be a great event, or something, for me to leave," Johnson said, describing how the disease has transformed his life from international travel and long work hours to rarely leaving his flat.
Johnson's initial symptoms included heavy legs, balance problems, and coordination issues that were initially mistaken for intoxication. "There were a few odd things, like getting turned away from a department store, always seeming like the drunkest person at a party," he recalled.
Treatment Landscape Disparity
The stark contrast between treatment options for different forms of MS highlights the urgent need for progressive MS research. Dr. Emma Gray, head of clinical trials at the MS Society, emphasized this disparity: "We have had a huge revolution of treatment with people with the relapsing MS, with 20-plus treatments now available. Some are better than others, there are some side effects of course, but what is still to crack, and why we need this campaign, is to find treatments for those tens of thousands of people that have progressive MS, and to stop it getting worse."
Funding and Future Prospects
The MS Society is supporting the trial through their Stop MS Campaign, recognizing the critical importance of developing effective treatments for progressive forms of the disease. The adaptive trial design offers the potential for faster drug development compared to traditional approaches, as researchers are not developing medications from scratch but rather testing existing compounds with known safety profiles.
Johnson, one of the first participants enrolled in the trial, remains optimistic despite not knowing whether he is receiving active treatment or placebo. "The trial gives him and others at least some hope," highlighting the psychological benefit of participating in cutting-edge research for a condition with limited therapeutic options.
The Octopus trial's innovative methodology could serve as a model for future neurological disease research, potentially accelerating the development of treatments for other conditions with significant unmet medical needs.
