A large focus in research regarding multiple sclerosis is how to protect from inflammation-mediated damage to the myelin sheath that acts as a barrier for the neuronal axons. Therefore, it is important to find effective remyelinating agents.
Recently, one has been discovered in an unexpected form – clemastine fumarate, an over-the-counter antihistamine.
The recent research
Jonah R. Chan, PhD is the vice chief of the Division of Neuroinflammation and Glial Biology and a Debbie and Andy Rachleff Distinguished Professor of Neurology. He is the senior author of the study, and the first to suggest clemastine fumarate, a drug that has been available to treat allergies for over twenty years, might be a method of treatment for multiple sclerosis.
A crossover study was conducted by UC San Francisco scientists that analyzed fifty patients who were experiencing relapsing multiple sclerosis. All patients remained on their preexisting immunomodulatory therapy, but one group was randomly chosen to take clemastine fumarate, while the other was given a placebo for three months, followed by two months of treatment. Both the researchers and patients were unaware throughout the duration of the study of which group had the placebo and which was actively taking the drug. Even after the switch, neither was aware. This form of control was especially effective, increasing the study’s statistical relevance and power.
Chan explains the initial reaction to the study: “People thought we were absolutely crazy to launch this trial, because they thought that only in newly diagnosed cases could a drug like this be effective – intuitively, if myelin damage is new, the chance of repair is strong. In the patients in our trial the disease had gone on for years, but we still saw strong evidence of repair.”
For more information, the results of the Phase II trial have been published in The Lancet, and are available online. The study was supported generously by the Rachleff family.
Importance of myelin
Myelin acts as a catalyst to electrical signals in the nervous system, making its strength instrumental in the health of those with the condition. MS affects around 2.5 million people internationally, and occurs when one’s immune system assaults myelin, which is many layers of fatty membrane that sits surrounding nerve fibers.
Myelin damage tends to progress throughout patients’ experiences with the disease, which results in neurons losing their transmission capabilities regarding electrical signals. This directly affects the patient by harming vision, balance, strength, mobility, and coordination.
The study showed profound results
The researchers showed that clemastine fumarate offers the first-ever proven drug-induced myelin repair in multiple sclerosis – or any chronic neurodegenerative condition for that matter.
Other treatments have attempted to protect the immune system from the progression of the destruction, but have not been able to actively repair the myelin. Restoring nervous system function impacts those with multiple sclerosis tremendously, and should offer relief to many.
Read on to learn more about these surprisingly positive results, and what they mean for the future of multiple sclerosis care and clinical research.
Effects of the drug on the group with MS
They found there to be much less visual-evoked potential latency delay in those who had received the clemastine fumarate.
The visual system is considered both one of the earliest and most prominent areas impacted by the condition. This delay is also used to confirm a diagnosis of multiple sclerosis, making it a clear indicator into the efficacy of the drug. Myelin regeneration results in the restoration of neural function, which is why a new study, named the ReBUILD trial, has been started.
Even those who switched from the placebo saw improvement
Even those who received the placebo at first and then switched to the clemastine fumarate had consistent responses.
The team watched over each group when taking the drug, and found that the neural signal that leads from the eye all the way to the back of the brain was directly impacted. They found this reaction to be particularly accelerated when compared to the baseline taken before the start of the study. Not only did this reaction occur in those who were initially taking the drug, but also those who had switched to placebo; what this means is that the regeneration of myelin is not only accessible during current use of the drug, but has long-lasting effects, making the antihistamine even more potent against multiple sclerosis.
MRIs present a temporary challenge
The team attempted to observe the regeneration of myelin directly via magnetic resonance imaging, or MRI, but the technique proved incapable of offering them access into this visual. Chan explained, “we still don’t have imaging methods that have been proven to be able to detect remyelination in humans.” However, that does not mean that their results are null or void; the researchers note that myelin regeneration is the only way to explain the results found in the VEPs, as it is able to act as a catalyst to neural transmission. This concept is present throughout neurobiology, and is a cornerstone of Chan’s preclinical research. Therefore, just because the MRI has proven to be too weak for direct observation does not mean that their hypothesis did not occur.
The drug is a great choice for those with multiple sclerosis who want to fight against neuron damage due to its powerful properties, but also lack of side effects. Fatigue is often present with those who take the drug, but nothing more serious has been reported to be connected.
No need to wait for approval
What is especially notable about this study is that, as opposed to trials that take years to offer access into useful treatments, the drug is available over-the-counter and is already FDA-approved, meaning that thousands of patients can begin to reap the benefits without waiting for long periods of time.
This research is the first of its kind
Ari Green, MD, is the principal investigator of the trial and explained the importance of the study: “To the best of our knowledge this is the first time a therapy has been able to reverse deficits caused by MS. It’s not a cure, but it’s a first step towards restoring brain function to the millions who are affected by this chronic, debilitating disease.”
Future implications are promising
Green, who is also chief of the Division of Neuroinflammation and Glial Biology, and a Debbie and Andy Rachleff Distinguished Professor of Neurology, and medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center, continues in his explanation of their results: “This is the first step in a long process. By no means do we want to suggest that this is a cure-all. We want to ground-truth myelination metrics – we’re designing the crucible that’s going to be used to test any future method for detecting myelination.”
While it may not be a cure-all, the progress this study has offered is sizable, and inspires hope in many with multiple sclerosis.