At its heart, multiple sclerosis is believed to occur when rogue immune cells attack myelin – a fatty coating that surrounds nerve cells in the brain and spinal cord. But what if these deviant immune cells could be taught to leave myelin alone? Or the immune system reprogrammed to fight these cells off? This is what researchers are hoping to do as they bring an age-old technology, vaccines, to bear in the treatment of MS.
When you think of vaccination, your mind probably goes to the shots you received as a child that were meant to protect you against certain bacterial or viral infections. Today, scientists are trying to adapt this same technology (with a few tweaks of course) to help stop autoimmune attacks. In the last few years a number of MS-focused vaccines have shown promising results in early phase clinical trials, and with each success the technology is closer than ever to offering a viable treatment option.
Source: James Gathany [Public domain], via Wikimedia Commons
Multiple sclerosis is a deeply personal disease. No two people experience MS in exactly the same way, and while the underlying autoimmune event that attacks myelin is consistently at the core of the MS disease process, the signs, symptoms, and progression of the disease can vary enormously from person to person.
In the same vein, every person living with MS responds to treatments in her or his own way. A little over twenty years ago, there were no therapies available that could alter the course of the disease and reduce the number of relapses and brain lesions; today, 11 disease-modifying therapies are approved for relapsing-remitting MS in Canada with several others in the pipeline. A wide selection of disease-modifying therapies is ideal in that it means more options that can manage the individual needs of people living with MS. Despite the crucial advancements in treatment options for MS, some people do not respond to the treatments that are available, which again speaks to the varying nature of the disease.
Jennifer Molson, a participants in the Canadian BMT Trial (Credit: The Ottawa Hospital)
Ongoing research is helping to expand the arsenal of treatment options for MS, while placing greater emphasis on a more personalized approach to treating the disease. The publication of the results from the Canadian Bone Marrow Transplantation (BMT) Trial in The Lancet represents the culmination of an extensive and collaborative effort funded by the MS Society of Canada’s affiliated Multiple Sclerosis Scientific Research Foundation (MSSRF) to identify a potential treatment for MS involving stem cells. The trial involved a procedure in which selected volunteers living with MS were given high-dose chemotherapy to dismantle the disease-causing immune system, followed by transfusion of their own stem cells to rebuild a healthy immune system that no longer attacks myelin. Given the risks associated with the procedure, individuals who were selected for the trial were those experiencing highly aggressive, inflammatory relapsing-remitting MS that did not respond to available treatments.
Our understanding of the genetic basis of multiple sclerosis has taken off over the past few years. Admittedly, the first link between MS and our genes was made in the early 1970s when scientists identified a set of immune-related genes that they found to be associated with an increased risk of MS. However, it wasn’t until the last ten years that a combination of advances in genetic sequencing technology, the bringing together of large population datasets, and bolstered by insights from the genetic blueprint constructed by the Human Genome Project, really put MS genetics on the map. Today, researchers to date have discovered over 100 genetic variants that have been linked to an increased risk of MS, and the overwhelming majority of these variants contain instructions for making proteins that influence the immune system. Individually, these variants only influence risk by a very small degree, and researchers are continuing to piece together the ways in which these genes interact and how they’re influenced by the environment to build up to a tipping point for triggering MS.
At the same time that scientists have been searching for genetic risk factors for MS, another story has been gradually unfolding since the 1980s looking at how MS is inherited within families. A pioneer in this field is Dr. Dessa Sadovnick from the University of British Columbia, who’s devoted her career to answering the question of why and how MS appears to cluster among relatives in certain families. Her early studies gathered enough evidence to build a strong case for receiving a $2.2 million grant by the MS Society and its affiliated MS Scientific Research Foundation to fund The Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS). A crucial outcome of this project was the development of one of the largest and richest MS genetic databases in the world encompassing over 30,000 people with MS and their relatives from 15 MS Clinics across Canada.
Since 2009, people around the world have marked the last Wednesday of every May in their calendar as World Multiple Sclerosis Day. Launched by the Multiple Sclerosis International Federation, World MS Day is an annual campaign that supports and connects the 2.3 million people living with MS across the globe with the goal of raising awareness and taking action to end MS.
This year’s World MS Day revolves around the theme of independence. For some people living with MS, independence means not having to rely on others for anything. For others, it means having the freedom of choice, even if one of those choices is accepting the support of others. Every person has their own definition of what independence means to them, and this year we’re celebrating all forms of independence for all people affected by MS.
The precise causes of multiple sclerosis continue to baffle the scientific community, although in general most researchers agree that a combination of genes and environmental factors appear to play a role in influencing the risk of developing MS. In those people living with MS, there is a great deal of research ongoing that’s looking at different types of exposures that can impact the course of the disease, such as the rate of relapses, severity, and progression. At AAN, a handful of researchers took to the podium to present their latest findings about the genetic and environmental factors that affect the risk of MS and play a role in modifying disease course.
Between 2 – 5% of multiple sclerosis cases emerge before the age of 18. Research into MS in children and adolescents – referred to as pediatric-onset MS – is not only important for managing the disease in youth, but can also provide insights into some of the earliest triggers and drivers of MS, with implications for understanding and treating MS across all groups. Since MS is believed to spring from a combination of specific genetic and environmental factors, invited speakers at the pediatric-onset MS seminar session presented new data exploring these factors in children and adolescents.
The conversations taking place on the third day at AAN shifted gears from the day before, placing the focus back on multiple sclerosis and exploring existing treatment strategies for people living with MS in great depth. Specific questions that were brought up include: does stopping immune-modifying treatment in those transitioning into secondary progressive MS affect persistent relapses? How commonly do clinicians switch their patients’ first treatment regimen, and why? What are the effects of specific DMTs on pregnancy outcomes in expectant mothers? Continue reading to learn some of the answers to these questions based on the most recent research findings:
One of today’s sessions placed the focus squarely on neuromyelitis optica (more recently expanded to be called neuromyelitis optica spectrum disorder, or NMOSD), a rare autoimmune disorder of the central nervous system (CNS) in which the spinal cord and/or optic nerves are attacked and damaged by specific antibodies. While far less common than MS, NMOSD can sometimes be confused with MS due to similar clinical features, although NMOSD attacks are often more severe than MS relapses. Two of the most common symptoms experienced by people living with NMOSD are inflammation of the optic nerve (called optic neuritis) which causes blurring or loss of vision in one or both eyes, and inflammation of the spinal cord (transverse myelitis), which can lead to a host of symptoms including arm and leg weakness, muscle spasms, bladder and bowel problems, and pain.
Since NMOSD and MS are fundamentally different diseases that require their own unique set of diagnostic criteria and treatment strategies, the panel brought together researchers at the forefront of NMOSD research to present their latest findings with the view to improve our understanding and management of the disease.
This year’s AAN conference is filled to the brim with programming, with sessions starting bright and early at 6:30 am and continuing well into the evening to accommodate the staggering amount of new information pouring out of the labs and clinics of researchers around the world. Headlining the MS program for Day 1 was a series of presentations about new insights into MS gained from animal and cell studies. Although modeling disease necessarily reduces the complex mechanisms underlying MS into simplified models by design, these types of studies are crucial for uncovering important clues about the genes and molecules that can trigger and/or drive MS and for rapidly screening new therapeutics with the potential to treat MS by combating harmful inflammation, repairing damage in the brain and preventing injury from occurring in the first place. The evening poster presentations were a departure from the morning’s seminar series, shifting the focus from basic laboratory research towards observations about risk factors that both influence the likelihood of developing MS and predict how the disease changes over time in those already living with MS.
This year, more than 10,000 neurologists and basic researchers from all over the world are converging on the stunningly beautiful city of Vancouver to attend the American Academy of Neurology (AAN) 68th annual meeting. Over the next few days, they’ll be resisting the temptation to hike in the nearby mountains or stroll along the winding ocean-side paths to focus on presenting their latest cutting-edge work to peers, exchange information and ideas, and form collaborations with the goal of advancing diagnosis and treatment of neurological diseases. The conference also offers intensive education programming so that clinicians can test their knowledge and stay up to date on the best clinical practices for disease treatment and management.
Although multiple sclerosis is one of many topics that will be covered at AAN alongside dementia, epilepsy, stroke, neuromuscular disorders and other neurological diseases, there are plenty of seminars and poster sessions about MS to keep the research team and I busy over the next several days. Among the topics to be covered include: new insights from animal and cell models, treatment strategies and clinical outcomes, risk factors, advanced imaging techniques, pediatric MS, and the latest findings from clinical trials. Of course, Canadian researchers will be represented in strong numbers at the various sessions – a true testament to Canada’s reputation of punching above its weight when it comes to the breadth and depth of its MS research productivity.
Be sure to check in frequently for routine updates as I distill down the scientific details into digestible summaries and key findings. Follow me on Twitter at @Dr_KarenLee (hashtag: #AANAM) for live updates as they unfold. And of course, drop any comments or questions below.