Dr. Karen Lee's Blog https://drkarenlee.ca An Inside Look at MS Research Sat, 03 Feb 2018 22:03:50 +0000 en-US hourly 1 https://wordpress.org/?v=4.6.10 120353486 ACTRIMS 2018: Cutting Edge Development in MS Research https://drkarenlee.ca/actrims-2018-cutting-edge-development-in-ms-research/ https://drkarenlee.ca/actrims-2018-cutting-edge-development-in-ms-research/#comments Sat, 03 Feb 2018 22:03:50 +0000 https://drkarenlee.ca/?p=1694 Presenters at the cutting-edge developments in MS session deliver the newest key findings of pivotal studies. At the session, we heard about a novel therapeutic involved in remyelination, pathways that inhibit remyelination, a genetic risk factor that may also target the cell functions in the central nervous system, and reduced adverse events with extended interval dosing of an approved disease-modifying therapy.

Read on for highlights from the #ACTRIMS2018 cutting edge developments in MS research session.

Oligodendrocytes

Nanocrystalline Gold as a novel therapeutic for remyelination in multiple sclerosis

Current therapies in MS are immunosuppressive—targeting both the good and bad immune  cells to prevent additional damage of the myelin. While these therapies are beneficial in slowing down progression of MS, they do not restore the lost function by repairing myelin by myelin-producing cells called oligodendrocytes. Oligodendrocyte precursor cells (cells that are immature and have not developed in mature myelin producing cells; OPCs) are detected around the lesions, yet it has been a challenging task to promote OPCs to mature. Dr. Michael Hotchkin from Clene Nanomedicine presented a novel treatment for the maturation of OPCs into oligodendrocytes—with the goal of promoting remyelination and improving symptoms. The therapeutic? The team developed a novel preparation of crystalline gold (Au) nanoparticles (CNM-Au8). While the mechanism of action of this therapy is being explored, Dr. Hotchkin believes it may be through regulating energy levels. In two different animal models of MS, Hotchkin presented robust remyelination response following CNM-Au8 treatment. Furthermore, Hotchkin showed restored behavioural function following demyelination. Therefore, CNM-Au8 is a promising new therapeutic candidate for MS—hence a human phase II clinical trial will commence in 2018.

IFN-γ signaling is a novel pathway that regulates oligodendrocytes precursor cells maturation

Oligodendrocyte precursor cells are being studied extensively in MS due to their potential to mature and promote remyelination. In this talk, Leslie Kirby (Johns Hopkins School of Medicine in Baltimore Maryland) presents a novel mechanism involved in preventing OPCs from maturing into myelin-producing oligodendrocytes. The signaling pathway of interest? IFN-γ. IFN-γ is a protein involved in cell-to-cell signaling, its levels are increased during MS activity, and administration of IFN-γ is shown to aggravate clinical disease resulting in increased number of relapses. Using a variety of methods, Kirby presents IFN-γ signaling in OPCs results in the enrichment of MHC class I antigen (set of cell surface proteins essential to recognize foreign molecules). Furthermore, IFN-γ signaling in OPCs was shown to activate toxic T-cells that led to cell death and suppression of remyelination.

Potential genetic risk factor in MS may also drive astrocyte function in development of lesions

Variations in multiple genes are thought to contribute to MS risk. However, whether these genes also impact cell function in the central nervous system remains unknown. Dr. Gerald Ponath (Yale University, New Haven, Connecticut) presents on a genetic risk variant, called rs7665090-G, driving astrocyte function in MS. Using induced pluripotent stem cells (adult cells that are pushed back to their stem cell fate) differentiated to the astrocytic fate that have this risk variant, Ponath showed enhanced NF-kB signaling (pro-inflammatory pathway this is thrown out of balance in MS) which results in recruitment of lymphocytes and toxicity. The risk variant directly perturbs central nervous system (CNS) cell functions through astrocytes, suggesting an interplay between the peripheral immune system and the CNS.

Extended interval dosing of Tysabri is associated with reduced progressive multifocal leukoencephalopathy risk

Inflammatory T cells enter the central nervous system by attaching to the blood-brain barrier with “sticky molecules”, called alpha-4 integrins. Approved treatment, Natalizumab (aka Tysabri), blocks alpha-4 integrin and prevents T cells from entering the central nervous system, where they cause inflammation and damage to myelin. Tysabri has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). PML is fatal viral disease that causes progressive damage or inflammation of the white matter of the brain and can result in disability or death. Dr. Lana Zhovtis Ryerson (NYU Langone Health, New York University, New York) examined if extended interval dosing (EID) of Tysabri could reduce the risk of PML.  The recommended dosage for Tysabri is 300mg, intravenously, every four weeks which was considered standard dosing (SD) in Dr. Ryerson’s paradigm. EID was based on dosing intervals greater than 5 weeks and less than 12 weeks. Of note, only people with MS who had anti-JC virus antibody were included in the analysis. The presence of anti-JCV increases PML risk. 13,132 individuals on SD and 1988 on EID were analyzed for the risk of PML. Ryerson showed a significant reduction in PML risk in  the EID group compared to SD group. As the efficacy of Tysabri was not collected in this group, the benefit-risk of EID treatment was not assessed.

These new findings are sure to make a splash in MS. Where do you think the future of cutting-edge development lies? Leave a comment below.

 

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ACTRIMS 2018: What are some emerging concepts in MS? https://drkarenlee.ca/actrims-2018-what-are-some-emerging-concepts-in-ms/ https://drkarenlee.ca/actrims-2018-what-are-some-emerging-concepts-in-ms/#comments Sat, 03 Feb 2018 02:27:34 +0000 https://drkarenlee.ca/?p=1687 5950870236_64af74c06d_o

Human T-cell

Gut microbiome, blood brain barrier, risk factors—these are all emerging concepts in MS. Scientists have immersed themselves in research in these areas because of the promise they hold in finding a cure for MS.  In fact, in the past couple of decades, there has been a remarkable expansion of new treatments for MS, novel imaging techniques that allow for earlier and quicker diagnosis, and great new ideas that all started as an “emerging concept”. In this session, researchers present the new ideas/concepts that inform us about how MS works, factors involved in MS and new ways to measure and capture disease activity and treatment options for people with MS.

While current treatment in MS function by managing and reducing the number of relapses by modulating aspects of the immune system, progression continues. Therefore, researchers like Dr. Kristen Evonuk (Cleveland Clinic) is looking at ways to protect the neurons that are damaged with new therapies for MS. Examining the link between excitotoxicity (the process through which neurons are damaged or killed due to over stimulation) in oligodendrocytes and MS, Dr. Evonuk’s project examined if stopping excitotoxicity would prevent damage of myelin in an animal model of MS. Inhibiting excitotoxicity in an animal model of MS, specifically in oligodendrocytes, resulted in improved clinical scores and reduced myelin damage. Furthermore, there was no change in the number of infiltrating T cells suggesting that protection of myelin occurs independently of altering the immune system. Dr. Evonuk’s work supports that excitotoxicity is a mechanism involved in damage that occurs in MS.

Dr. Adil Harroud from the lab of MS Society funded researcher, Dr. Brent Richards, investigated the effect that age at puberty has on susceptibility of developing MS. Puberty is already associated with an increased incidence (and emergence of more females with MS compared to males) of MS, however, the role of puberty on the risk of developing MS is unknown. The current research in this area is contradictory—some groups have identified increased risk of MS with earlier age of puberty while other have found no associations. Some have even found a delayed onset of MS with earlier age of puberty. Dr. Harroud stated that studies of different groups may be confounded due to factors such as obesity which impacts both time of puberty and risk of developing MS. Performing a meta-analysis involving over 300,000 women, Dr. Harroud examined if age of puberty increased the odds of developing MS and if the puberty effects of MS were mediated by body mass index (BMI). This study revealed that decreased age at puberty increases the odds of developing MS—in fact one year decrease in the onset of puberty increased the odds of developing MS by 8%. Furthermore, the association between puberty and age were found to be mediated due to the effects of puberty timing with BMI.

Dr. Evelyn PeelenCurrent techniques for identifying and visualizing immune cells in brain lesions are limited, with only 3-4 markers available. The need for additional techniques so that we can better profile the cells that are disease causing in MS are needed. A postdoctoral fellow funded by the MS Society of Canada, Dr. Evelyn Peelen from Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CHUM), presented a method through which different immune cells and type of lesion could be identified within a single MS brain lesion. Using postmortem tissue, she took one third of the lesion to characterize the type of lesion (pre-active, active, chronic) by staining the tissue with different colours based on the chemistry of the tissue. The remainder of the tissue was analyzed through a method called flow cytometry, a laser based technique employed to sort different types of cells.  Dr. Peelen was able to detect five different subsets of T cells, macrophages, dendritic cells and five different subsets of B cells—all of which have been implicated in MS. Furthermore, this technique showed changes in the amount of different types of cells in cortical lesions compared to active white matter lesions allowing for the characterization immune cells in different lesions.

What emerging concepts interest you? Leave a comment below!

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Leading researchers and clinicians gather to present their work at the third annual ACTRIMS Forum https://drkarenlee.ca/leading-researchers-and-clinicians-gather-to-present-their-work-at-the-third-annual-actrims-forum/ https://drkarenlee.ca/leading-researchers-and-clinicians-gather-to-present-their-work-at-the-third-annual-actrims-forum/#respond Tue, 30 Jan 2018 20:47:43 +0000 https://drkarenlee.ca/?p=1682 ACTRIMS Forum logo

The research team is on site again for another year of reporting on the latest and hottest news presented at the annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2018. This year’s meeting is held in San Diego, California from February 1-3.

Themed, “Therapeutic Targets in MS: the Frontier and Future of Disease Modifying Therapy,”, the forum is packed with leading researchers/clinicians presenting on hot topics in the field. Emerging concepts in the pathology, risk factors and imaging tools are sure to be news-worthy. Sessions are also planned on different cells—lymphocytes, microglia, macrophages, astrocytes and oligodendrocytes—and what role they play in MS.  Moreover, the session on cutting-edge developments with topics such as novel therapeutics, and genetic influences of MS are for sure to be of interest. For more information, visit the ACTRIMS Forum 2018 site.

Stay tuned for more updates on #ACTRIMS2018 over the next few days, both here on the blog and on Twitter at @Dr_KarenLee.

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Happy New Year! Here are my three top research moments of 2017! https://drkarenlee.ca/happy-new-year-here-are-my-three-top-research-moments-of-2017/ https://drkarenlee.ca/happy-new-year-here-are-my-three-top-research-moments-of-2017/#respond Mon, 08 Jan 2018 15:54:41 +0000 https://drkarenlee.ca/?p=1675 new year post

Happy New Year! It’s the time of year many of us make that list of New Year’s resolutions whether it’s being healthier, getting organized, being happier or something else. For many of you affected by MS, one hope you have is to stay well through your very personal journey.

Happily, 2018 seems promising for another year of discoveries. The MS Society continues to fund some of the world’s most groundbreaking MS research—research that has improved quality of life for people affected by MS. So here’s to another year of life-changing scientific advances like those we saw in 2017:

  1. The publication of the results of the minocycline clinical was one of the biggest highlights of 2017. This MS Society-funded clinical trial showed that minocycline reduces the risk of developing clinically definite MS in individuals with early signs of MS. Since treating a first clinical demyelinating event as early as possible is a key step in reducing the likelihood of developing MS, the possibility of access to an effective and low-cost treatment like minocycline is extremely exciting. This unique Canadian research study was designed and conducted by Canadian researchers and involved Canadian patients. The MS Society of Canada and MS Society Scientific Research Foundation have been behind this work from start to end-from funding the initial basic biomedical science study published by Dr. V. Wee Yong and his team in 2002 to the most recent success of Dr. Metz and her team in the final phase III clinical trial. See the news update for details.
  2. Health Canada approved two disease modifying therapies (DMTs) for the treatment of relapsing-remitting MS. In August, Roche’s Ocrevus™ which targets white blood cells called B cells -known to be involved in the abnormal immune response in MS- was approved based on the results from two pivotal phase III clinical trials called OPERA I and OPERA II. Health Canada also approved EMD Serono’s disease modifying therapy, Mavenclad™ (oral cladribine) which selectively targets and accumulates in certain types of white blood cells (lymphocytes), such as disease-causing T cells. Approval of Mavenclad™ by Health Canada is based on results from the phase III clinical trial called CLARITY. With the approval of these two DMTs, there are now 15 disease-modifying therapies available for Canadians diagnosed with RRMS.
  3. Going from the bench-to-bedside is no swift or easy feat as the minocycline story above shows. Promising results from the bench or discovery phase rarely make it to the translational phase as it requires careful research to assess if the drug will be safe and effective. Funding of translational research has declined, resulting in a critical gap that has caused the translation of new research discoveries into treatments to fall behind. The MS Society of Canada is addressing this gap by supporting research in the translational phase. In 2017, we continued our collaboration with Fast Forward (a non-profit subsidiary of the National MS Society- U.S) and Centre for Drug Research and Development (CDRD) to fund two more promising projects. With Fast Forward, the MS Society funded Fang Liu from the Centre for Addiction and Mental Health (CAMH) in Toronto, Ontario for the top-ranked proposal testing drug-like compounds that could be used to halt the neurodegenerative process in MS. Dr. Phillipe Séguéla will work with CDRD to identify compounds that could limit neurodengeration in progressive MS by targeting the way that cells in the brain communicate with each other. By collaborating these two organizations are leveraging their expertise in drug development; funding from the MS Society will enable the advancement of their research through a critical stage of preclinical development towards a transformative treatment option.

With these exciting discoveries and developments in 2017, I can’t wait to see what 2018 has in store for us in research and innovation in MS.

Wishing everyone a happy and healthy 2018!

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Late-breaking session at #MSParis2017 unveils advances in human anatomy, a new biomarker, and clinical trial results for Progressive MS https://drkarenlee.ca/late-breaking-session-at-msparis2017-unveils-advances-in-human-anatomy-a-new-biomarker-and-clinical-trial-results-for-progressive-ms/ https://drkarenlee.ca/late-breaking-session-at-msparis2017-unveils-advances-in-human-anatomy-a-new-biomarker-and-clinical-trial-results-for-progressive-ms/#comments Tue, 19 Dec 2017 21:22:04 +0000 https://drkarenlee.ca/?p=1671 As per yearly tradition, the 7th joint ECTRIMS/ACTRIMS meeting ended with late-breaking research news. This year, we heard about discoveries related to human brain anatomy, a new biomarker for phase 2 clinical trials and a potential drug for progressive MS.

Dr. Danny Reich: Lymphatic vessels are discovered using imaging techniques

The lymphatic system’s function is to remove dead cells and waste from the body’s organs. Lymphatic vessels run alongside blood vessels and transport a colourless fluid that contains infection-fighting immune cells and waste called lymph.   Dr. Danny Reich, a senior investigator at the National Institute of Neurological Disorders and Stroke, reported the existence of previously unknown lymphatic vessels in the brain of human and nonhuman primates. High-resolution Magnetic Resonance Imaging (MRI) scans were obtained from five healthy human volunteers and three primates. Imaging revealed the presence of lymphatic vessels in the outermost layer of the brain and spinal cord, called the dura mater. This discovery may shed light on how the brain expels waste, holding promise for a better understanding of the normal physiology of lymphatic drainage from the brain and spinal cord and potential abnormalities in neurological diseases.

Dr. Maria Pia Sormani: Neurofilament light chain (NfL) is a promising biomarker in phase II clinical trials

NfL is one of the proteins of the neural cytoskeleton (which supports the shape of the cell), and helps in the growth of axons or nerve fibers commonly damaged in MS. Following damage to the axons, NfL levels in the cerebrospinal fluid change and are thus considered a promising biomarker of injury in neurological disorders. Dr. Maria Pia Sormani, a researcher at the University of Genoa, and her team explored whether NfL could be used as an outcome measure in Phase 2 clinical trials for relapsing-remitting MS. They analyzed the levels of NfL in participants of the FREEDOMS study (a clinical trial testing the efficacy of Gilenya). Their data showed a decrease in NfL in individuals taking fingolimod compared to those on placebo. NfL may qualify as an informative and convenient endpoint for future Phase 2 clinical studies as it can capture both inflammatory and degenerative aspects of MS.

Dr. Robert Fox: Ibudilast shows potential for progressive MS, is well-tolerated, and slows brain atrophy compared to placebo

Treatment options for progressive MS are still limited but there has been a recent increase in treatments for progressive MS in the research pipeline. Ibudilast, which reduces inflammation in nerve cells by targeting pro-inflammatory signaling pathways, was tested for potential use in progressive MS. Dr. Robert Fox, a neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic, and a team of researchers analyzed the safety, tolerability and efficacy of ibudilast. In phase 2 of the SPRINT (Secondary and Primary Progressive Ibudilast NeuroNEXT Trial) -MS trial, 255 participants with either primary or secondary progressive MS were randomized to receive either ibudilast (up to 100mg) or placebo. The study met its primary outcome by reducing brain atrophy by 48% compared to placebo. Ibudilast was reported as being safe and well-tolerated, with gastrointestinal symptoms (nausea, diarrhea, abdominal pain or vomiting) seen as the most common adverse events.

Have a question or comment about the late-breaking news? Leave it below.

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MSParis2017: The gut continues to be an area of active MS research https://drkarenlee.ca/msparis2017-the-gut-continues-to-be-an-area-of-active-ms-research/ https://drkarenlee.ca/msparis2017-the-gut-continues-to-be-an-area-of-active-ms-research/#respond Mon, 18 Dec 2017 14:14:16 +0000 https://drkarenlee.ca/?p=1668 Bacteria backgroundThe trillions of bacteria that call the intestines home collectively make up the gut microbiome. Bacteria in the gut do much more than digest food and break it down into nutrients; they are involved in many biological functions including metabolic processes and regulating aspects of our immune system. Researchers are learning that these tiny creatures are important in the general maintenance of good health and are incredibly sensitive to change. Disruption of gut bacteria has been implicated in a host of health conditions including diabetes, obesity and autoimmune diseases like inflammatory bowel disorder and multiple sclerosis (MS). Studies have shown that certain strains of bacteria are elevated in individuals with MS but not in healthy individuals. We will be hearing more about the role the gut microbiome plays in the development, prevention, and treatment of MS in the coming years.

Already, the gut microbiome was an area of great interest at the #MSParis2017 conference this year. Here are highlights of the research discussed in the talks of Dr. Hartmut Wekerle and Dr. Helen Tremlett.

Dr. Hartmut Wekerle: The composition of the gut microbiome may be a trigger for MS

 Dr. Hartmut Wekerle, an Emeritus Director at the Max Planck Institute of Neurobiology in Munich, was interested in the connections between the gut microbiome and brain and how these interactions may trigger MS. Dr. Wekerle used a mouse model of MS to test the connections between the two in what he called the “Munich twin trial.” Dr. Wekerle initially compared the gut composition of 34 pairs of human identical (or monozygotic) twins in which one twin had MS and the other twin was not impacted by the disease. He found an increase in a bacterial species called Akkermansia, a species that is currently being studied by other researchers for its effects on metabolism, obesity, diabetes and inflammation. Dr. Wekerle and his research team then transplanted fecal matter from the healthy twin and the twin with MS into healthy mice known to be susceptible to MS.  The fecal matter from the healthy twin induced MS in 30% of these mice, whereas MS developed in 60% of the mice that received fecal transplant from a twin with MS. Dr. Wekerle’s team also measured the microbial profiles of the mice, producing two important findings in the mice with a fecal transplant from a twin with MS.  The mice showed decreases in the normal levels of an organism in the gut called Sutterella, which has been previously shown to regulate the immune response. They also showed a decrease in normal levels of interleukin 10, an anti-inflammatory molecule. The work performed by Dr. Wekerle and his team suggests that the components of the microbiome contribute to the development of MS. This work was recently published in the renowned journal Proceedings of the National Academy of Sciences.

Dr. Helen Tremlett: Triggers and facilitators of MS in children with MS

Dr. Helen Tremlett’s (University of British Columbia) research interest lies in the role the gut may play in triggering or facilitating MS. In a group of kids with MS, Dr. Tremlett set out to explore two primary questions: (1) Do the gut micro-organisms that make up the microbiome differ in kids with pediatric MS from kids without MS? and (2) Is the composition of the microbiome in the gut associated with future relapse risk in pediatric MS?

A population of pediatric MS patients affords researchers the opportunity to study the disease process at very early stages of MS.  Dr. Tremlett measured the composition of the gut microbiome in 15 children with MS and compared it with nine children without MS. Her research team aimed to discover any differences in the relationship between the developing gut microbiota and certain cells of the immune system known to be markers.  Dr. Tremlett and her team discovered correlations between the diversity of gut microbiota and the presence of markers from the immune system in children without MS. However, these correlations were not identified in children who have MS suggesting that the relationship between the gut microbiome and immune system can impact the development of MS.

In another study, Dr. Tremlett examined whether the relapse rate in pediatric MS was associated with alterations in the gut microbiome. The research team discovered that depletion of a bacteria called Fusobacteria in children with MS was associated an earlier relapse compared with children who had this bacterium. Interestingly, Fuscobacteria was previously correlated with immune system markers in children without MS but not those with MS.

The gut microbiome influences the risk of developing MS as well as progression in MS-and it may be possible to modify it. But first many questions remain to be answered. What key microorganisms in the gut regulate the immune system? What mechanism(s) allows for the associations between the gut and MS? Researchers around the world are eagerly pursuing the needed data.

Have a question/comment on this hot topic? Leave it below.

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Aging and comorbidities: a hot topic at the #MSParis2016 conference https://drkarenlee.ca/aging-and-comorbidities-a-hot-topic-at-the-msparis2016-conference/ https://drkarenlee.ca/aging-and-comorbidities-a-hot-topic-at-the-msparis2016-conference/#respond Fri, 15 Dec 2017 20:35:15 +0000 https://drkarenlee.ca/?p=1666 Comorbidities (when someone is living with more than one condition) are common in MS and can affect people at the onset of their disease, and are even more prevalent in the aging MS population. Evidence presented at the 7th Joint ECTRIMS/ACTRIMS meeting in Paris, France on October 24-28, 2017 by Dr. Ruth Ann Marrie (University of Manitoba) suggests that comorbidities are associated with a negative impact on outcomes including an increase in disability progression, hospitalizations, mortality and a change in response to fatigue management. Aging is associated with certain comorbidities in the general population, and is no different in people living with chronic conditions such as MS. The most common comorbidities for people with MS were diabetes, heart disease, hypertension (high blood pressure), hyperlipidemia (high cholesterol) and peripheral vascular disease. In the aging MS population, comorbidities may appear at a time when disability progression is increasing and management of the disease is more challenging.

According to a separate Canadian study[1], the number of people living with MS over the age of 55 is increasing. It is postulated that this is due to improved quality of life of patients and the availability of more effective treatments for MS.

As people living with MS age, the risk of certain comorbidities increases. The need for multi-disciplinary, patient-centred care for prevention and treatment of comorbidity in people living with MS is critical in the overall management of the disease, especially within the aging MS population.

[1] Ploughman M, Beaulieu S, Harris C, et al. The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results. BMJ Open 2014;4: e005718. doi:10.1136/ bmjopen-2014-005718

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2017 revisions to MS diagnostic criteria presented at #MSParis2017 conference https://drkarenlee.ca/2017-revisions-to-ms-diagnostic-criteria-presented-at-msparis2017-conference/ https://drkarenlee.ca/2017-revisions-to-ms-diagnostic-criteria-presented-at-msparis2017-conference/#comments Mon, 11 Dec 2017 21:26:11 +0000 https://drkarenlee.ca/?p=1660 checklistThe McDonald criteria for MS was first established in 2001 by neurologist Ian McDonald and his team of researcher to diagnose individuals with MS with speed and sensitivity. The criteria include guidelines on Magnetic Resonance Imaging (MRI) evidence, clinical exams and the use of cerebrospinal fluid (fluid found in the brain and spinal cord, collectively called the central nervous system or CNS) to assist with the diagnosis of MS. Since then, it has undergone three separate revisions; the first took place in 2005, the second in 2010 and most recently, in 2017. The International Panel on Diagnosis of MS revised the 2010 McDonald criteria which was presented at the 7th Joint ECTRIMS/ACTRIMS meeting in Paris, France on October 24-28, 2017. The 2017 revisions were spurred by new data/research since the 2010 revision was released and now allow for an earlier and more efficient diagnosis of MS. The new data has lead to: a better understanding of MS including diagnostic strategies with more sensitivity, greater knowledge of conditions that mimic MS (which can result in misdiagnosis) and revised MRI criteria. The 2017 criteria lessen the risk of misdiagnosis, and most importantly, people can be diagnosed earlier and begin treatment right away.

The revisions include both symptomatic and asymptomatic MRI lesions whereas only asymptomatic lesions were applied in the 2010 criteria meaning now all lesions will be counted and considered. Also in the 2010 criteria, evidence of dissemination in time (more than one neurological attack at different points in time) and dissemination in space (lesions on separate areas of the CNS) were required to make a diagnosis of MS. Using the 2017 criteria, a diagnosis of MS in a person with clinically isolated syndrome or CIS, can be made based on evidence of dissemination of space and the presence of at least two oligoclonal bands (OBs) in the cerebrospinal fluid, which indicate inflammation. Presence of the OBs can replace the need for evidence of dissemination in time, allowing for earlier diagnosis and treatment plan. The criteria have further expanded potential lesion areas within the CNS to include cortical (outer most layer of the brain) and optic nerve (transmits visual information from the retina to the brain) lesions. In addition, the 2017 criteria provide more sensitivity for more accurate diagnoses in pediatric, Latin American and Asian patients.

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Researchers at #MSParis2017 talk about the factors regulating the Blood Brain Barrier in MS https://drkarenlee.ca/researchers-at-msparis2017-talk-about-the-factors-regulating-the-blood-brain-barrier-in-ms/ https://drkarenlee.ca/researchers-at-msparis2017-talk-about-the-factors-regulating-the-blood-brain-barrier-in-ms/#respond Wed, 22 Nov 2017 19:15:19 +0000 https://drkarenlee.ca/?p=1655 BBBThe blood-brain barrier (BBB) was highlighted in a session at the #MSParis2017 conference where researchers presented their recent findings on the relationship between the BBB and MS. The BBB is a network of cells (called endothelial cells) that line all the blood vessels in the brain. These cells are so tightly connected that they prevent harmful substances such as bacteria and toxins from entering the brain and spinal cord (collectively called the central nervous system or CNS).  In MS, the BBB is compromised and becomes leaky, allowing white blood cells from the immune system to pass through the barrier and enter the CNS. The white blood cells then attack myelin (the coating around the nerve cells in the CNS) which results in inflammation and lesions. Many research teams are examining what causes the BBB to weaken and ways to prevent this from happening.

Dr. Alexandre Prat: DICAM is a novel molecule that promotes the migration of harmful immune cells to the brain and spinal cord

MS Society funded researcher, Dr. Alexandre Prat from Centre de Recherche du Centre Hospitalier de l’Université de Montréal, talked about the factors that may regulate the movement of white blood cells from the blood to the CNS. One of these factors is the presence of cell adhesion molecules (CAMs) which are proteins found on the surface of immune cells that enable them to adhere to and cross over the BBB.  Dr. Prat and his research team have discovered a specific CAM, called DICAM, that may assist in orchestrating immune cells to accomplish this invasion. DICAM was found in the tissues of people with RRMS and is associated with the production of pro-inflammatory factors on white blood cells. Furthermore, Dr. Prat showed that reducing the quantity of DICAM prevented the migration of harmful immune cells into the CNS and hence delayed the onset of disease in a mouse model of MS. The data presented by Dr. Prat identified DICAM –a novel molecule that is found on white blood cells that promotes their migration across the BBB and into the CNS, where they cause damage.

Elizabeth Gowing: integrin α8 is a protein that is involved in facilitating the migration of immune cells into the central nervous system.

We also heard from Elizabeth Gowing – a PhD student in Dr. Alexandre Prat’s lab and the recipient of an MS Society PhD studentship award. Her research looks at proteins called integrins which facilitate the migration of cells across the BBB. She discovered a specific integrin, called integrin α8 is involved in several ways.  Gowing’s work shows integrin α8 (1) is linked to an increased quantity in pro-inflammatory immune cells, (2) is found in active MS lesions in the CNS, and (3) blocking integrin α8 decreases the migration of harmful immune cells into the CNS of mice that have MS like disease.

A member of my team also had a chance to talk to Elizabeth Gowing at the conference to find out a bit about what motivated her to get involved in research in MS and more about her project. Here is their conversation (8:14 minutes):

 

Catherine Larochelle: epidermal growth factor-like protein 7 (EGFL7) is a novel protein player that limits the infiltration of pro-inflammatory immune cells in MS

Following in the footsteps of her doctoral supervisor, Dr. Alexandre Prat, Dr. Catherine Larochelle, now a scientist at the Université de Montréal, examined the role of epidermal growth factor-like protein 7 (EGFL7) in regulating the migration of immune cells in MS. EGFL7 was previously demonstrated to enhance endothelial cell (cells lining the BBB) survival under stressful conditions. Dr. Larochelle discovered that EGFL7 can limit the amount of CNS infiltration of pro-inflammatory immune cells into the CNS by promoting BBB integrity and securing activated immune cells to the perivascular space (space that spans between blood vessels and brain matter) to prevent their migration into the CNS. Therefore, Dr. Larochelle believes that EGFL7 could represent a new therapeutic target in MS.

The studies presented at this session are important steps to finding out more about the BBB so that future studies can focus on how the BBB can be strengthened to prevent immune cells from entering the CNS, ultimately putting a halt on progression.

Have any questions or comments? Leave them below!

 

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Bonjour Paris! World’s leading researchers and clinicians gather in Paris for largest MS conference https://drkarenlee.ca/bonjour-paris-worlds-leading-researchers-and-clinicians-gather-in-paris-for-largest-ms-conference/ https://drkarenlee.ca/bonjour-paris-worlds-leading-researchers-and-clinicians-gather-in-paris-for-largest-ms-conference/#respond Wed, 25 Oct 2017 13:28:01 +0000 https://drkarenlee.ca/?p=1646 Palais Des CongresThe MS Society of Canada’s research team has arrived in the exciting city of Paris, France to attend the 7th Joint ACTRIMS/ECTRIMS meeting from October 25-28, 2017. Paris tidbit: Jean Martin Charcot, who identified and named multiple sclerosis (la sclérose en plaques), is from Paris, France. The ACTRIMS/ECTRIMS Congress is the largest international meeting devoted to scientific research and health management of multiple sclerosis, and each year the list of topics and number of participants grows.

With over 9,000 participants from over 100 countries attending the meeting with a record number of abstracts at 2,080, the conference is bound to provide the latest information in research and clinical trial outcomes. Themes for this year’s meeting include the revised diagnostic criteria, biomarkers in MS, neuroimmunology, symptom management in MS, and emerging strategies to promote repair, just to name a few.  Selected abstracts will be presented throughout the week at poster sessions (researchers showcase their data on posters and engage in discussions) and scientific sessions (presentations that are delivered to a larger audience). The conference also includes smaller workshops and education sessions for nurses, junior neurologists in training, and media.

The conference is a great platform for announcing breaking news in MS research and treatment, and provides an opportunity for researchers, clinicians and trainees to share the hottest data from their laboratories.

This year the research team will be delivering live updates throughout the week via Twitter(@Dr_KarenLee), Facebook (Multiple Sclerosis Society of Canada), and my blog. We are excited to hear about the latest advances in MS and report it to our MS Community.

Stay tuned for more updates and feel free to leave questions or comments below.

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