Contributor Ramtin Hakimjavadi
There is no denying that London, Ontario is and has long been a hub for groundbreaking multiple sclerosis (MS) research. Some of today’s the most exciting work is being conducted by researchers at Western University. Indeed, at London Health Sciences Centre’s University Hospital, Dr. Marcelo Kremenchutzky and Dr. Ana Cristina Wing dedicate their time to translating findings in basic research into medical practice, in an effort to make meaningful health outcomes for MS patients. Currently, their focus is on the first fecal microbiota transplantation (FMT) study on humans to investigate gut bacteria as a potential therapy for MS. MS is a potentially disabling immune-mediated neurodegenerative disease of the central nervous system (CNS). Signs and symptoms are often unpredictable given that lesions (damage to tissue) may occur anywhere in the CNS, and the disease most often affects young adults. Spasticity, tremor, cognitive impairment or fatigue are some of the common manifestations of the disease. Canadians have among the highest rates of MS in the world. There was a time when a diagnosis of MS was catastrophic, but this is no longer necessarily the case. Although there is currently no cure, many treatments — called disease-modifying therapies (DMTs) — have been developed over the past several decades. These therapies serve to significantly improve the quality of life for patients and alter the disease course by reducing MS disease activity. More recently, efforts are being directed towards research in neuroregeneration. In his twenty years as the Director of the London MS Clinic, Dr. Kremenchutzky established all the pivotal trials that lead to the approval of currently available treatments in MS in Canada and the World. Today, in collaboration with research fellow Dr. Wing, they are conducting pioneering research of the microbiome in relation to MS. They hope to find out if FMT is a viable treatment for MS patients. The relationship between the gut and various neurological diseases is an idea that is gaining popularity in neuroscience. Recently, some have argued that the manipulation of the human gut microbiome has therapeutic potential.
Dr. Wing said: “We already have a lot of research showing that [the gut microbiome of MS patients] seems to be different compared to the gut of people that do not have MS”. And we don’t exactly know why and how these differences relate to the disease.” This is what they have set out to determine. Currently, they are in the process of conducting a crossover phase II clinical trial. Two groups, an early intervention group and a late intervention group, are administered an FMT followed by monthly checkups for a year. The goal is to monitor the effectiveness of the treatment over a meaningful period of time and also to record any notable side effects.
“Since this is a phase II study, we are only looking for inflammation”, said Dr. Wing. “So, basically, we are going to measure the cytokine levels in the serum to see if they change somehow in a more anti-inflammatory pattern.” In collaboration with several laboratories at Western in immunology, the microbiome, and infectious disease, the work of Dr. Kremenchutzky and Dr. Wing could serve as a potential proof of concept. Their efforts build from past research that has established the therapeutic potential of FMT for other conditions. It has been shown that the colitis caused by antibiotic resistant Clostridium difficile infection (CDI) can be treated with FMT. Dr. Wing believes that this exploratory study will help address preliminary questions about the viability of such a treatment for MS patients.
“When we do this transfer successfully, we are able to restore a healthy composition in the gut […] if we transplant healthy bacteria from an individual that does not have MS into a patient that does have MS, are we able to change the microbiome? How will this influence inflammation?”
Answering these questions will open opportunities for future studies to ask more specific questions regarding FMT as a therapy for MS. “I think it is a very innovative and bold project. Because it has never been done before in MS,” said Wing. Despite the promise of this endeavor, Dr. Wing noted that the wider research community was initially reluctant to accept the idea of treating MS patients with FMT. “We do see some skepticism from people […] and some believe that we need more information before trying FMT with MS.” Fortunately, the early results have been promising. The patients have been responding well to the treatment. In Dr. Ana Wing’s view, the value of research is not predicated on obtaining the expected results. Rather, she believes any research is helpful regardless of whether the outcome is positive or negative. Ultimately, all pursuits of knowledge contribute to building a foundation for future studies. “We are going to learn something from this experience, I have no doubt of that … whatever works, or does not work, we will improve on it for next time.” For a disease that affects 2.3 million people worldwide, the importance of Drs. Kremenchutzky and Wing’s research cannot be overstated. Such developments in MS therapies makes one hopeful for the future of battling with a condition whose progression can be so unforgiving. For more information, visit the following links: https://clinicaltrials.gov/ct2/show/NCT03183869
Shortly after writing this article, it was discovered, with great sadness, the passing of Dr. Kremenchutzky on Monday, October 1st, 2018. A memorial service was held in London, ON, on Saturday, October 13th, 2018 at 1:00 p.m. Those wishing to make a donation in Dr. Kremenchutzky’s memory are asked to consider Lung Cancer Canada. The family wishes to extend a special ‘thank you’ to Dr. Mark Vincent, the London Regional Cancer Program and the Stroke Unit at University Hospital