Posts tagged MS
Posts tagged MS
For some, the disease multiple sclerosis (MS) attacks its victims slowly and progressively over a period of many years. For others, it strikes without warning in fits and starts. But all patients share one thing in common: the disease had long been present in their nervous systems, hiding under the radar from even the most sophisticated detection methods. But now, scientists at the Gladstone Institutes have devised a new molecular sensor that can detect MS at its earliest stages—even before the onset of physical signs.
In a new study from the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, scientists reveal in animal models that the heightened activity of a protein called thrombin in the brain could serve as an early indicator of MS. By developing a fluorescently labeled probe specifically designed to track thrombin, the team found that active thrombin could be detected at the earliest phases of MS—and that this active thrombin correlates with disease severity. These findings, reported online in Annals of Neurology, could spur the development of a much-needed early-detection method for this devastating disease.
MS, which afflicts millions of people worldwide, develops when the body’s immune system attacks the protective myelin sheath that surrounds nerve cells. This attack damages the nerve cells, leading to a host of symptoms that include numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease’s underlying causes—causes that researchers are only just beginning to understand.
Last year, Dr. Akassoglou and her team found that a key step in the progression of MS is the disruption of the blood brain barrier (BBB). This barrier physically separates the brain from the blood circulation and if it breaks down, a blood protein called fibrinogen seeps into the brain. When this happens, thrombin responds by converting fibrinogen into fibrin—a protein that should normally not be present in the brain. As fibrin builds up in the brain, it triggers an immune response that leads to the degradation of the nerve cells’ myelin sheath, over time contributing to the progression of MS.
"We already knew that the buildup of fibrin appears early in the development of MS—both in animal models and in human patients, so we wondered whether thrombin activity could in turn serve as an early marker of disease." said Dr. Akassoglou, who directs the Gladstone Center for In Vivo Imaging Research (CIVIR). She is also a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "In fact, we were able to detect thrombin activity even in our animal models—before they exhibited any of the disease’s neurological signs."
Scientists are gaining a new level of understanding of multiple sclerosis (MS) that may lead to new treatments and approaches to controlling the chronic disease, according to new research released today at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
MS is a severe, often crippling, autoimmune disease caused by the body’s immune system attacking the nervous system. Today, more than two million people worldwide suffer from MS and other neuroinflammatory diseases. MS usually strikes in early adulthood and manifests with symptoms including vision loss, paralysis, numbness, and fatigue. The disease can be intermittent or progressive and currently has no cure.
Today’s new findings show that:
Other recent findings discussed show that:
“The findings shown today represent real promise for the millions suffering from MS,” said press conference moderator Jeffrey Rothstein of Johns Hopkins University and an expert in neurodegenerative diseases. “These studies are breakthroughs in understanding and treating a disease that remains uncured, difficult to diagnose, and for which it is very difficult to prevent progression.”
Researchers used magnetic resonance imaging to quantify brain tissue volume, a critical measurement of the progression of multiple sclerosis and other diseases.
Imagine that your mechanic tells you that your brake pads seem thin, but doesn’t know how long they will last. Or that your doctor says your child has a temperature, but isn’t sure how high. Quantitative measurements help us make important decisions, especially in the doctor’s office. But a potent and popular diagnostic scan, magnetic resonance imaging (MRI), provides mostly qualitative information.
An interdisciplinary Stanford team has now developed a new method for quantitatively measuring human brain tissue using MRI. The team members measured the volume of large molecules (macromolecules) within each cubic millimeter of the brain. Their method may change the way doctors diagnose and treat neurological diseases such as multiple sclerosis.
"We’re moving from qualitative – saying something is off – to measuring how off it is," said Aviv Mezer, postdoctoral scholar in psychology. The team’s work, funded by research grants from the National Institutes of Health, appears in the journal Nature Medicine.
Mezer, whose background is in biophysics, found inspiration in seemingly unrelated basic research from the 1980s. In theory, he read, magnetic resonance could quantitatively discriminate between different types of tissues.
"Do the right modifications to make it applicable to humans," he said of adapting the previous work, "and you’ve got a new diagnostic."
Previous quantitative MRI measurements required uncomfortably long scan times. Mezer and psychology Professor Brian Wandell unearthed a faster scanning technique, albeit one noted for its lack of consistency.
"Now we’ve found a way to make the fast method reliable," Mezer said.
Mezer and Wandell, working with neuroscientists, radiologists and chemical engineers, calibrated their method with a physical model – a radiological “phantom” – filled with agar gel and cholesterol to mimic brain tissue in MRI scans.
The team used one of Stanford’s own MRI machines, located in the Center for Cognitive and Neurobiological Imaging, or CNI. Wandell directs the two-year-old center. Most psychologists, he said, don’t have that level of direct access to their MRI equipment.
"Usually there are many people between you and the instrument itself," Wandell said.
This study wouldn’t have happened, Mezer said, without the close proximity and open access to the instrumentation in the CNI.
Their results provided a new way to look at a living brain.
MRI images of the brain are made of many “voxels,” or three-dimensional elements. Each voxel represents the signal from a small volume of the brain, much like a pixel represents a small volume of an image. The fraction of each voxel filled with brain tissue (as opposed to water) is called the macromolecular tissue volume, or MTV. Different areas of the brain have different MTVs. Mezer found that his MRI method produced MTV values in agreement with measurements that, until now, could only come from post-mortem brain specimens.
This is a useful first measurement, Mezer said. “The MTV is the most basic entity of the structure. It’s what the tissue is made of.”
The team applied its method to a group of multiple sclerosis patients. MS attacks a layer of cells called the myelin sheath, which protects neurons the same way insulation protects a wire. Until now, doctors typically used qualitative MRI scans (displaying bright or dark lesions) or behavioral tests to assess the disease’s progression.
Myelin comprises most of the volume of the brain’s “white matter,” the core of the brain. As MS erodes myelin, the MTV of the white matter changes. Just as predicted, Mezer and Wandell found that MS patients’ white matter tissue volumes were significantly lower than those of healthy volunteers. Mezer and colleagues at Stanford School of Medicine are now following up with the patients to evaluate the effect of MS drug therapies. They’re using MTV values to track individual brain tissue changes over time.
The team’s results were consistent among five MRI machines.
Mezer and Wandell will next use MRI measurements to monitor brain development in children, particularly as the children learn to read. Wandell’s previous work mapped the neural connections involved in learning to read. MRI scans can measure how those connections form.
"You can compare whether the circuits are developing within specified limits for typical children," Wandell said, "or whether there are circuits that are wildly out of spec, and we ought to look into other ways to help the child learn to read."
Tracking MTV, the team said, helps doctors better compare patients’ brains to the general population – or to their own history – giving them a chance to act before it’s too late.
A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging” was published on Nov. 1 in Plos One. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.
The study investigated the neural correlates of cognitive fatigue in MS utilizing three neuroimaging approaches: functional magnetic resonance imaging (fMRI), which allows researchers to look at where in the brain activation is associated with a task or an experience; diffusion tensor imaging (DTI), which allows researchers to look at the health of the brain’s white matter; and voxel-based morphometry (VBM), which allows researchers to investigate structural changes in the brain. These three approaches were used to examine how likely it is for an individual to report fatigue(“trait” fatigue), as well as the fatigue an individual feels in the moment (“state” fatigue). This study is the first to use neuroimaging to investigate these two, separable aspects of fatigue.
“We looked specifically at the relationship between individuals ‘self-reported fatigue and objective measures of cognitive fatigue using state-of-the-art neuroimaging,” explained Helen M. Genova, Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. “The importance of this work lies in the fact that it demonstrates that the subjective feeling of fatigue can be related to brain activation in specific brain regions. This provides us with an objective measure of fatigue, which will have incalculable value as we begin to test interventions designed to alleviate fatigue.”
In Experiment 1, patients were scanned during performance of a task designed to induce cognitive fatigue. Investigators looked at the brain activation associated with “state” fatigue. In Experiment 2, DTI was used to examine where in the brain white matter damage correlated with increased “trait” fatigue in individuals with MS, as assessed by the Fatigue Severity Scale (FSS). The findings of Experiments 1 and 2 support the role of a striato-thalamic-frontal cortical system in fatigue, suggesting a “fatigue-network” in MS.
“Identifying a network of fatigue-related brain regions could reframe the current construct of cognitive fatigue and help define the pathophysiology of this multifaceted yet elusive symptom of MS,” said John DeLuca, Ph.D., VP of Research & Training at Kessler Foundation. “Replication of these findings with larger sample sizes will be an important next step.”
Kessler researchers find aerobic exercise benefits memory in persons with multiple sclerosis
A research study headed by Victoria Leavitt, Ph.D. and James Sumowski, Ph.D., of Kessler Foundation, provides the first evidence for beneficial effects of aerobic exercise on brain and memory in individuals with multiple sclerosis (MS). The article, “Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings,” was released as an epub ahead of print on October 4 by Neurocase: The Neural Basis of Cognition. The study was funded by Kessler Foundation.
Hippocampal atrophy seen in MS is linked to the memory deficits that affect approximately 50% of individuals with MS. Despite the prevalence of this disabling symptom, there are no effective pharmacological or behavioral treatments. “Aerobic exercise may be the first effective treatment for MS patients with memory problems,” noted Dr. Leavitt, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. “Moreover, aerobic exercise has the advantages of being readily available, low cost, self-administered, and lacking in side effects.” No beneficial effects were seen with non-aerobic exercise. Dr. Leavitt noted that the positive effects of aerobic exercise were specific to memory; other cognitive functions such as executive functioning and processing speed were unaffected.
The study’s participants were two MS patients with memory deficits who were randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. Baseline and follow-up measurements were recorded before and after the treatment protocol of 30-minute exercise sessions 3 times per week for 3 months. Data were collected by high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Aerobic exercise resulted in a 16.5% increase in hippocampal volume, a 53.7% increase in memory, and increased hippocampal resting-state functional connectivity. Non-aerobic exercise resulted in minimal change in hippocampal volume and no changes in memory or functional connectivity.
“These findings clearly warrant large-scale clinical trials of aerobic exercise for the treatment of memory deficits in the MS population,” said James Sumowski„ Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation.
While it’s been known for over a century that iron deposits in the brain play a role in the pathology of Multiple Sclerosis (MS), new imaging research from Western University (London, Canada) helps to answer the question of whether these accumulations are a cause or consequence of the disease. The study led by Ravi Menon, PhD, of the Robarts Research Institute found iron deposits in deep gray matter, suggesting the accumulation occurs very early in the disease course. The researchers also found evidence casting further doubt on the controversial liberation therapy for MS. The research is in early publication online in Multiple Sclerosis and Related Disorders.
Menon and PhD candidate Matthew Quinn used 3-Tesla Magnetic Resonance Imaging (MRI) to scan 22 patients with clinically isolated syndrome (CIS). These are patients who’ve had a single clinical attack, at least half of whom will go on to be diagnosed with MS. The others may have a different disease. Sixteen age and sex matched controls were also studied.
"We wanted to know if the iron deposits happen early in the process, or whether it’s something that accumulates with time as the disease progresses," says Menon, who holds a Canada Research Chair in Functional Magnetic Imaging. "We also studied the veins that drain from the brain and looked for a correlation between the diameter of of these veins and iron accumulation. One of the reasons to do this, of course was the hypothesis proposed by Paolo Zamboni that if you had narrow jugular veins, this would give rise to additional iron and in turn cause MS."
The scientists found iron deposits in the CIS group were well above the amounts found in the control group. The MRIs also revealed for the first time, subtle damage to the brain’s white matter even at this early stage. The researchers also found no correlation between the iron deposits and diameter of the veins.
"So while the iron in the brain correlates with the disability of the subjects, the iron in the brain does not correlate with the actual diameter of the jugular veins. So the Zamboni hypothesis is incorrect as far as the iron being related to some kind of obstruction." Menon found narrowed veins in the control group as well as the CIS group, and both groups had narrower veins on one side compared to the other.
Menon hopes this imaging research will lead to the earlier diagnosis of MS. He plans to follow the patients every four months for the next two years, to see retrospectively, what characterizes those patients that go on to be diagnosed with MS compared to those who do not.
"We’re looking at a couple of different approaches to diagnostics using this imaging research. In suspected MS cases –the very first time they appear in clinic, if they have an abnormally high amount of iron in the frontal cortex of the brain –that’s probably a pretty good sign they have MS or some other white matter disease." This research was funded primarily by the Canadian Institutes of Health Research.
MS is the most common neurological disease affecting young adults, with symptoms that include loss of balance, impaired speech, double vision, extreme fatigue and paralysis.
Scientists at The Scripps Research Institute (TSRI) have identified a set of compounds that may be used to treat multiple sclerosis (MS) in a new way. Unlike existing MS therapies that suppress the immune system, the compounds boost a population of progenitor cells that can in turn repair MS-damaged nerve fibers.
One of the newly identified compounds, a Parkinson’s disease drug called benztropine, was highly effective in treating a standard model of MS in mice, both alone and in combination with existing MS therapies.
“We’re excited about these results, and are now considering how to design an initial clinical trial,” said Luke L. Lairson, an assistant professor of chemistry at TSRI and a senior author of the study, which is reported online in Nature on October 9, 2013.
Lairson cautioned that benztropine is a drug with dose-related adverse side effects, and has yet to be proven effective at a safe dose in human MS patients. “People shouldn’t start using it off-label for MS,” he said.
A New Approach
An autoimmune disease of the brain and spinal cord, MS currently affects more than half a million people in North America and Europe, and more than two million worldwide. Its precise triggers are unknown, but certain infections and a lack of vitamin D are thought to be risk factors. The disease is much more common among those of Northern European heritage, and occurs about twice as often in women as in men.
In MS, immune cells known as T cells infiltrate the upper spinal cord and brain, causing inflammation and ultimately the loss of an insulating coating called myelin on some nerve fibers. As nerve fibers lose this myelin coating, they lose their ability to transmit signals efficiently, and in time may begin to degenerate. The resulting symptoms, which commonly occur in a stop-start, “relapsing-remitting” pattern, may include limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression, among other problems.
Current therapies, such as interferon beta, aim to suppress the immune attack that de-myelinates nerve fibers. But they are only partially effective and are apt to have significant adverse side effects.
In the new study, Lairson and his colleagues decided to try a complementary approach, aimed at restoring a population of progenitor cells called oligodendrocytes. These cells normally keep the myelin sheaths of nerve fibers in good repair and in principle could fix these coatings after MS damages them. But oligodendrocyte numbers decline sharply in MS, due to a still-mysterious problem with the stem-like precursor cells that produce them. “Oligodendrocyte precursor cells (OPCs) are present during progressive phases of MS, but for unknown reasons don’t mature into functional oligodendrocytes,” Lairson said.
A 100,000-Molecule Screen
Using a sophisticated small-molecule screening laboratory that TSRI manages in conjunction with the California Institute of Regenerative Medicine and in collaboration with the California Institute for Biomedical Research (Calibr), Lairson and his team screened a library of about 100,000 diverse compounds for any that could potently induce OPCs to mature or “differentiate.”
Several compounds scored well as OPC differentiation-inducers. Most were compounds of unknown activity —but one, benztropine, had been well characterized and indeed was already FDA-approved for treating Parkinson’s disease. “That was a surprise, and it meant that we could move forward relatively quickly in testing it,” said graduate student Vishal A. Deshmukh, first author of the paper who performed most of these experiments.
With the help of Brian R. Lawson, a senior author of the paper and assistant professor of immunology at TSRI, and his colleague Research Associate Virginie Tardif, Deshmukh set up tests of benztropine in mice with an induced MS-like autoimmune disease—a model commonly used for testing prospective MS drugs.
In these tests, benztropine showed a powerful ability to prevent autoimmune disease and also was effective in treating it after symptoms had arisen—virtually eliminating the disease’s ability to relapse. Although benztropine on its own worked about as well as existing treatments, it also showed a remarkable ability to complement these existing treatments, in particular two first-line immune-suppressant therapies, interferon-beta and fingolimod.
“Adding even a suboptimal level of benztropine effectively allowed us, for example, to cut the dose of fingolimod by 90%—and achieve the same disease-modifying effect as a normal dose of fingolimod,” said Lawson. “In a clinical setting that dose-lowering could translate into a big reduction in fingolimod’s potentially serious side effects.”
In further analyses, the researchers confirmed that benztropine works against disease in this mouse model by boosting the population of mature oligodendrocytes, which in turn restore the myelin sheaths of damaged nerves—even as the immune attack continues. “The benztropine-treated mice showed no change in the usual signs of inflammation, yet their myelin was mostly intact, suggesting that it was probably being repaired as rapidly as it was being destroyed,” said Lawson.
Benztropine is known to have multiple specific effects on brain cells, including the blocking of activity at acetylcholine and histamine receptors and a boosting of activity at dopamine receptors. But Lairson and his colleagues found evidence that the drug stimulates OPCs to differentiate mainly by blocking M1 or M3 acetylcholine receptors on these cells.
In addition to setting up initial clinical trials, Lairson and his team hope to learn more about how benztropine induces OPC maturation, and how its molecular structure might be optimized for this purpose. “We’re also looking at some of the other, relatively unknown molecules that we identified in our initial screen, to see if any of those has better clinical potential than benztropine,” he said.
“This work, like our previous studies with hematopoietic and mesenchymal stem cells, illustrates the power of small molecules to control stem and precursor cells in ways that may ultimately lead to a new generation of drugs for regenerative medicine,” said Peter G. Schultz, the Scripps Family Chair Professor in the Department of Chemistry at TSRI and one of the study’s senior authors.
A study led by Dr. Anthony Traboulsee of the University of British Columbia and Vancouver Coastal Health to see whether narrowing of the veins from the brain to the heart could be a cause of multiple sclerosis has found that the condition is just as prevalent in people without the disease.
The results, published in the U.K. medical journal The Lancet, call into question a controversial theory that MS is associated with a disorder proponents call chronic cerebrospinal venous insufficiency (CCSVI).
The study used both ultrasound and catheter venography (an x-ray of the vein after injecting it with a dye) to examine the veins of people with MS, their unrelated siblings and unrelated healthy volunteers. Catheter venography is considered the most accurate, “gold standard” technology for revealing the size and shape of veins, says Traboulsee, an associate professor of Neurology at UBC and director of the MS Clinic at UBC Hospital of Vancouver Coastal Health.
By comparing the width of veins between the brain and the heart with a normal reference point taken from below the jaw, the researchers showed that at least two-thirds of each of the groups had narrowing of the extracranial veins that was greater than 50 per cent. Differences in rates of venous narrowing between the groups were not statistically significant.
“Our results confirm that venous narrowing is a frequent finding in the general population, and is not a unique anatomical feature associated with multiple sclerosis,” Traboulsee says. “This is the first study to find high rates of venous narrowing in a healthy control group, as well as the first to show that the ultrasound criteria usually used to ‘diagnose’ CCSVI are unreliable. The connection between venous narrowing and MS remains unknown, and it would certainly appear to be much more complicated than current theories suggest.”
TAU researchers find chemicals in marijuana could help treat MS
Multiple sclerosis is an inflammatory disease in which the immune system attacks the nervous system. The result can be a wide range of debilitating motor, physical, and mental problems. No one knows why people get the disease or how to treat it.
In a new study published in the Journal of Neuroimmune Pharmacology, Drs. Ewa Kozela, Ana Juknat, Neta Rimmerman and Zvi Vogel of Tel Aviv University’s Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases and Sackler Faculty of Medicine demonstrate that some chemical compounds found in marijuana can help treat MS-like diseases in mice by preventing inflammation in the brain and spinal cord.
"Inflammation is part of the body’s natural immune response, but in cases like MS it gets out of hand," says Kozela. "Our study looks at how compounds isolated from marijuana can be used to regulate inflammation to protect the nervous system and its functions." Researchers from the Weizmann Institute of Science co-authored the study.
Israel has a strong tradition of marijuana research. Israeli scientists Raphael Mechoulam and Yechiel Gaoni discovered THC, or tetrahydrocannabinol, in 1964, kick-starting the scientific study of the plant and its chemical constituents around the world. Since then, scientists have identified about 70 compounds — called cannabinoids — that are unique to cannabis and have interesting biological effects. In the 1990s, Prof. Vogel was among the first researchers to describe endocannabinoids, molecules that act like THC in the body.
Besides THC, the most plentiful and potent cannabinoid in marijuana is cannabidiol, or CBD. The TAU researchers are particularly interested in CBD, because it offers medicinal benefits without the controversial mind-altering effects of THC.
In a 2011 study, they showed that CBD helps treat MS-like symptoms in mice by preventing immune cells in their bodies from transforming and attacking the insulating covers of nerve cells in the spinal cord. After inducing an MS-like condition in mice — partially paralyzing their limbs — the researchers injected them with CBD. The mice responded by regaining movement, first twitching their tails and then beginning to walk without a limp. The researchers noted that the mice treated with CBD had much less inflammation in the spinal cord than their untreated counterparts.
High hopes for humans
In the latest study, the researchers set out to see if the known anti-inflammatory properties of CBD and THC could also be applied to the treatment of inflammation associated with MS — and if so, how. This time they turned to the immune system.
The researchers took immune cells isolated from paralyzed mice that specifically target and harm the brain and spinal cord, and treated them with either CBD or THC. In both cases, the immune cells produced fewer inflammatory molecules, particularly one called interleukin 17, or IL-17, which is strongly associated with MS and very harmful to nerve cells and their insulating covers. The researchers concluded that the presence of CBD or THC restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules’ ability to reach and damage the brain and spinal cord.
Further research is needed to prove the effectiveness of cannabinoids in treating MS in humans, but there are reasons for hope, the researchers say. In many countries, CBD and THC are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.
"When used wisely, cannabis has huge potential," says Kozela, who previously studied opiates like morphine, derived from the poppy plant. "We’re just beginning to understand how it works."
Study brings to 110 known risk factors and provides important insight into disease mechanism
Scientists of the International Multiple Sclerosis Genetics Consortium (IMSGC) have identified an additional 48 genetic variants influencing the risk of developing multiple sclerosis. This work nearly doubles the number of known genetic risk factors and thereby provides additional key insights into the biology of this debilitating neurological condition. The genes implicated by the newly identified associations underline the central role played by the immune system in the development of multiple sclerosis and show substantial overlap with genes known to be involved in other autoimmune diseases.
Published online September 29 in the journal Nature Genetics, the study, “Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis,” is the largest investigation of multiple sclerosis genetics to date. Led by the University of Miami Miller School of Medicine, this study relied upon an international team of 193 investigators from 84 research groups in 13 countries and was funded by more than 40 local and national agencies and foundations.
Multiple sclerosis (MS) is a chronic disabling neurological condition that affects over 2.5 million individuals worldwide. The disease results in patchy inflammation and damage to the central nervous system that causes problems with mobility, balance, sensation and cognition depending upon where the damage to the central nervous system occurs. Neurological symptoms are often intermittent in the early stages of the disease but tend to persist and progressively worsen with the passage of time for the majority of patients. The risk of developing multiple sclerosis is increased in those who have a family history of the disease. Research studies in twins and adopted individuals have shown that this increased risk is primarily the result of genetic risk factors.
The findings released in this study nearly double the number of confirmed susceptibility loci, underline the critical role played by the immune system in the development of multiple sclerosis, and highlight the marked similarities between the genetic architecture underlying susceptibility to this and the many other autoimmune diseases.
The present study takes advantage of custom designed technology known as ImmunoChip—a high-throughput genotyping array specifically designed to interrogate a targeted set of genetic variants linked to one or more autoimmune diseases. IMSGC researchers used the ImmunoChip platform to analyze the DNA from 29,300 individuals with multiple sclerosis and 50,794 unrelated healthy controls, making this the largest genetics study ever performed for multiple sclerosis. In addition to identifying 48 new susceptibility variants, the study also confirmed and further refined a similar number of previously identified genetic associations.
With these new findings, there are now 110 genetic variants associated with MS. Although each of these variants individually confers only a very small risk of developing multiple sclerosis, collectively they explain approximately 20 percent of the genetic component of the disease.
Explaining the significance of the work and the nature of the collaboration, the Miller School’s Jacob McCauley, Ph.D., who led the study on behalf of the IMSGC, said, “With the release of these new data, our ongoing effort to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step. By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies. These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal.”