THE NEUROLOGY COMMUNITY
TMF has partnered with some of the top Neurology Departments in the country to aid in the advancement of preventative treatments for Alzheimer’s, ALS, Parkinson’s, MS and other life-altering illnesses. We hope to diagnose sooner and ultimately find cures.
Meet the doctors in the respective communities we support.
Merit Cudkowicz, MD, MSc
Chief, Neurology Service, MGH.
Specializes in clinical trials for ALS therapies.
Rudy Tanzi, PHD
Vice- Chair, Neurology, MGH
Specializes in genetics and aging research.
Jonathan Rosand, MD, MSc
J.P. Kistler Neurologist and Chief, Neurocritical Care and Emergency Neurology, MGH
Specializes in stroke & traumatic brain injury.
Eric Klawiter, MD, MSc
Assistant Neurologist, MGH
Specializes in MS Research.
HOWARD L . WEINER, MD
Co-director, Ann Romney Center for Neurologic Diseases, BWH
Specializes in MS imaging and clinical evaluation
DENNIS J. SELKOE, MD
Co-director, Ann Romney Center for Neurologic Diseases, BWH
Specializes in Clinical trials for Alzheimer’s
WHY RESEARCH MATTERS
With the financial support of TMF, our research experts are breaking ground on innovative diagnostic tools, procedures and treatment options for patients. Take a look at what is being discovered right now:
MASS. GEN RESEARCH
+ Integrated Care for Optimal Brain Health
Dedicated to developing strategies to preserve and promote brain health and prevent brain disease. This truly dynamic and integrative approach will change the way we think about brain-healthy lifestyles.
The Institute for Brain Health (IBH) at Massachusetts General Hospital is dedicated to preserving and promoting brain health and preventing brain disease. The IBH is led by Dr. Jonathan Rosand, MD, PhD, a clinician and Chief of Neurocritical Care and Emergency Neurology at Mass General; Dr. Rudy Tanzi, PhD, a scientist and Vice-Chair for Research of the Department of Neurology at Mass General; and Dr. Greg Fricchione, MD, Director of the Benson-Henry Institute. The IBH brings together clinicians, investigators, scientists and therapists to provide patients with truly integrative care across three patient populations:
GREEN: healthy individuals motivated to preserve brain function Goals: preserve and promote brain health and prevent disease YELLOW: individuals at high risk for disease Goals: preserve / promote / prevent First-degree relatives Potent risk factors present (primary prevention) Recovering from brain disease/injury (secondary prevention) RED: individuals with active disease or brain injury Goals: preserve and restore brain function
By serving individuals who do not yet have active brain disease (the “green” and “yellow” populations), the IBH at Mass General fills a need not currently addressed by primary care or the neuroscience specialties, but analogous to the approach to prevention of heart disease and preservation of heart function, and to the screening for cancer, two cornerstones of modern primary care.
+ Therapeutic advances in Neurodegenerative Diseases
Our determined effort to find therapies to relieve the symptoms, stop the progression and cure diseases such as ALS, MS and Alzheimer’s disease require a better understanding of the disease biology. We are currently in the midst of 20 clinical trials including promising therapies for ALS, the possibility of a definitive blood test for diagnosing MS in addition to more accurate measurements of cognitive dysfunction in MS, and testing new therapies, including gene therapy, for earlier diagnosis of Alzheimer’s disease.
Amyotrophic Lateral Sclerosis (ALS): Drug development in ALS is risky and expensive, yet the need and urgency is great. Clinical trials in ALS in the past have failed primarily due to the limited understanding of what causes or accelerates the disease and the lack of well-validated treatment targets. It is much clearer now that ALS is not one illness, but likely represents several different disorders that all lead to the same clinical symptoms. The targets for treatments are much better defined, but there is still much to do.
Large pharmaceutical companies often do not invest in ALS until the later stages of drug development, when there are studies that show proof of mechanism, target engagement and preliminary effectiveness. As a result, most of the early promising therapies fall in the valley of death due to lack of funding. Philanthropy plays a significant role in allowing our MGH team to test promising targeted therapies quickly in patients and we have a Phase II Clinical Trial Fund dedicated to moving these trials forward.
We currently are enrolling people with ALS in more than 20 clinical research studies, including six clinical trials with novel therapies. The rest of the studies explore imaging or fluid markers to better understand the cause of illness and best targets for treatments. Funding at this stage of research can significantly advance our knowledge and allow us to gather critically important data, which can then be used to leverage funding from pharmaceutical partners or the NIH.
There are therapies today, based on great science and strong rationale, ready to move forward into clinical trials in our patients, but the lack of funding has stalled this critically important testing phase. Our goal is to bring these great therapeutic ideas from the laboratory to clinical trials for people with ALS.
+ Developing an Effective Blood Test for Multiple Sclerosis:
There is no definitive test for the diagnosis of multiple sclerosis (MS). Developing a blood test for the diagnosis and/or prognosis of MS will allow for the identification of the disease at an earlier stage. Understanding platelet signatures – known to be abnormal in neuroinflammation but not well studied in MS patients – may help establish the disease course of MS from this new biomarker standpoint.
Platelets exist in an activated state in MS, potentially promoting the traffic of immune cells across the blood-brain barrier. Blocking platelet receptors has been shown to reduce disease activity in the animal model most resembling MS. These early results suggest that platelets may have an important role in understanding MS disease activity and anti-platelet agents may play a therapeutic role. Funding for this study will allow Farrah Mateen, MD, PhD, to determine if there is a specific blood-based platelet RNA signature that can distinguish MS patients from non-MS patients; if the platelet messenger RNA signature changes in discernible ways during a clinical relapse among patients with MS; and if platelet RNA signatures differ among MS patients treated with specific disease-modifying therapies. This information will help identify the most effective therapies.
+ Accurate Measurement of Cognitive Dysfunction in MS:
Eric Klawiter, MD, MSc, is using a sophisticated imaging tool only available at Mass General to get a clearer picture of how MS prompts the immune system to attack the protective coating around nerve fibers and develop ways to protect them. Dr. Klawiter’s most recent work was accepted for presentation at an imaging conference in Vancouver in February, 2017. Further research will allow him to expand this study to a larger group of patients, providing critically important information and therapeutics that will discourage the immune system’s reaction.
Another focus of Dr. Klawiter’s research is using MRIs to evaluate cognitive dysfunction, a significant complaint in 50 percent of patients with MS. His team recently discovered that the areas of the brain most highly connected tend to have the most atrophy in patients with MS. More research into these connections will lead to a better understanding of therapies that can reduce atrophy and improve cognitive function for these patients.
+ Promising Therapies for Alzheimer’s Disease:
Neurogeneticist Rudy Tanzi, PhD, who found the first Alzheimer's disease gene in 1987, recently completed the Alzheimer’s Genome Project, an intensive effort to discover all the gene variants that increase a person’s risk of Alzheimer’s disease. Tanzi and his team are already using his revolutionary “Alzheimer’s in a dish” technique to quickly and efficiently apply this genetic information to identify prevention and treatment strategies and test their impact. By focusing initially on drugs already FDA-approved for another use, Tanzi’s team has identified several promising therapies that may reduce the accumulation of plaques, tangles, or neuroinflammation. Early administration of cromolyn sodium, approved for use with asthma, significantly decreased AD pathogenic aggregation-prone proteins in a transgenic mouse model of AD, and is now in phase 3 clinical trials in AD patients. In addition, Dr. Tanzi has developed a very promising anti-amyloid drug known as a “gamma secretase modulator,” which is expected to enter into human clinical trials later this year.
In addition, Brad Hyman, MD, PhD, is using sophisticated imaging tools to gain a better understanding on how AD progresses. He is also working with Dr. Tanzi using information from the Alzheimer’s Genome Project to focus on a rare mutation in the APOE AD-risk gene that protects people from developing AD. He is also developing techniques to edit genes, including APOE, to reduce the accumulation of proteins that cause neurons to die. This gene therapy program also has the benefit of providing the toolbox to take advantage of new targets, too. The Hyman team recently found they could protect the brain form amyloid-induced damage by using gene therapy to target the tau gene. We believe gene and cell therapy are soon going to help patients with Alzheimer’s in the same way they are already beginning to help cancer patients.
+ Early Diagnostics
All of these therapies will work best if applied early in the course of disease. A critical need, therefore, is developing new approaches to this problem – and the MGH Memory Disorders team has a major effort along these lines. Dr. Teresa Gomez Isla is helping to develop PET ligands that will find neurofibrillary tangles in early disease patients; Dr. Steve Arnold is searching for biomarkers with advanced proteomics and lipidomics approaches; Dr. Steve Gomperts is using electroencepholgrams, a classical tool in neurology, to tease out subtle changes that occur in the brain as damage begins; Dr. Mark Albers has invented a dramatically sensitive olfactory memory test that anticipates clinical symptoms by a few years, and Drs. Reisa Sperling and Doreen Rentz are developing new memory tests that are more sensitive and specific than the classic techniques used clinically. Teaming with neuroradiologists Bruce Rosen and his colleagues, the MGH Memory Disorders team is also exploring new MRI approaches to find the specific lesions of Alzheimer's at a very early stage.
+ Illuminating Neurodegenerative Disorders
New imaging technologies will create opportunities to study aspects of neurodegenerative diseases and immediately translate these discoveries to effective treatments.
One of the biggest challenges in ALS drug development is the lack of a mechanistic readout of drug efficacy in patients at early phases of clinical drug development.
A Mass General team led by Nazem Atassi, MD, is now building an exciting and diverse pipeline of mechanistic imaging platforms to be used as specific readouts of drug efficacy in many efficient and cost effective ALS clinical trials.
Similar imaging pipelines allowed the multiple sclerosis field to develop many successful and effective treatments that were approved in the past 10 years. Our goal is to replicate the MS successes in ALS by building imaging tools that are available for researchers and companies around the world to accelerate drug discoveries for ALS patients. This is already happening with the launch of three ALS clinical trials (Ibudilast, RNS60, AMX0035) using MGH imaging technologies. These advanced imaging technologies will open the window to study mechanism such as Inflammation, excitotoxicity and epigenetics in patients who suffer from the disease, and immediately translate these discoveries to effective treatments for ALS patients. We are eager to incorporate advanced imaging tools in more Phase II clinical trials to accelerate the pace of ALS drug discovery.
+ Multidisciplinary Care Clinics
Patient live longer and have a better quality of life when they are provided with comprehensive, socialized, sensitive care that addresses the patient’s health, as well as their family, work and social life.
Individuals with neurological diseases who receive care at a multidisciplinary clinic survive longer and have a better quality of life. At Mass General’s Multidisciplinary Care Clinic patients and their families are provided with comprehensive, specialized, sensitive care that addresses the patient’s health, as well as their family, work and social life. Care teams are comprised of clinicians from a variety of specialties and disciplines who work together to coordinate an individual patient’s care. Having a multidisciplinary care team also allows our patients to receive all their care in one place, often scheduling visits with multiple specialists in one day.
The Multidisciplinary Care Clinic team includes experts in physical therapy, respiratory therapy, nursing and social services. They work closely with our physicians to address and manage the range of issues patients may encounter. Insurance covers only a small portion of these services, with scheduling, coordination and specialized services such as speech and physical therapy either not covered at all or only covered for a percentage of the clinician’s time. Knowing the positive impact the multidisciplinary care approach has, not only on the patient’s quality of life, but also on the family caregivers, we are committed to making this available to every patient who needs it. Philanthropy allows us to serve the needs of every patient who comes to us.
+ Breaking New Ground In Brain Tumor Research
With only marginal improvements in survival rates over the past 30 years, new approaches are urgently needed to better treat this devastating disease. Dr. Krichevsky and her team are focused on the role of microRNA—small RNA molecules that regulate gene expression—in brain tumor development, as these molecules also represent a promising class of targets for tumor treatment. Widely recognized as a pioneer in the field, Anna Krichevsky, PhD, is spearheading innovative and encouraging research on malignant brain tumors. With only marginal improvements in survival rates over the past 30 years, new approaches are urgently needed to better treat this devastating disease. Dr. Krichevsky and her team are focused on the role of microRNA—small RNA molecules that regulate gene expression—in brain tumor development, as these molecules also represent a promising class of targets for tumor treatment. The team is focused specifically on miR-10b, a mciroRNA abundant in most brain tumors that promotes tumor growth and appears essential for the survival of tumor cells. The team has discovered a gene editing technique to eliminate miR-10b within the tumor, halting its activity and killing the cancer cells. Team members are now working to optimize this potentially lifesaving therapeutic strategy, which stands to provide a common therapy with widespread impact for the thousands of patients diagnosed with brain tumors each year.
+ Promising Advances Toward A Blood Test for Alzheimer's Disease
Using the most sophisticated technology available, Dr. Selkoe and his colleague Dominic Walsh, PhD, are working to detect proteins in the blood or cerebrospinal fluid that could serve as biomarkers for AD, including tau, the protein that makes up the “tangles” that accumulate in the brain and impair cognitive function in AD. Dennis Selkoe, MD, continues to advance efforts to identify and validate Alzheimer’s disease (AD) biomarkers, and then leverage those discoveries toward new tools for diagnosis, monitoring, and treatment. Using the most sophisticated technology available, Dr. Selkoe and his colleague Dominic Walsh, PhD, are working to detect proteins in the blood or cerebrospinal fluid that could serve as biomarkers for AD, including tau, the protein that makes up the “tangles” that accumulate in the brain and impair cognitive function in AD. They were able to successfully measure elevated tau levels in blood samples, suggesting that it may become possible to detect AD with a simple blood test. Such a test would offer the potential to detect AD even before symptoms develop, an extraordinary breakthrough that would allow for earlier intervention and improved outcomes in countless patients, as well as streamlined clinical trials.
+ Moving Toward a New Therapy for ALS
The study of microRNA, non coding RNA found in plants and animals, is leading to promising potential treatments to slow the progression of ALS.
Working closely with collaborators at Massachusetts General Hospital, Oleg Butovsky, PhD, is studying microRNA to develop potential new treatments for ALS. Dr. Butovsky and his team have focused their attention on miR-155, a microRNA molecule that plays a major role in regulating inflammation, and may be involved in the progression of ALS and other neurodegenerative conditions. Building on their studies showing that inhibiting miR-155 prolonged life in animal models and lowered levels in human cells, Dr. Butovsky and his team have partnered with miRagen Therapeutics—a biopharmaceutical company that specializes in developing microRNA-targeting therapies—to develop specific inhibitors to shut down miR-155 in humans. In the past year, they have identified two promising blockers that will soon be ready for clinical trials.
Brigham and Women's Research
+ Exploring The Gut-Brain Connection In Multiple Sclerosis
Existing research has suggested a connection between the gut microbiome—the collection of microorganisms that live in the intestine—and brain inflammation. But how the two are linked and how diet may influence this connection has remained largely unknown, until now.
In a new line of study led by Francisco Quintana, PhD, researchers have shown for the first time that changes in diet and the gut microbiome may influence the activity of astrocytes, star-shaped cells that reside in the brain and spinal cord and play a key role in controlling inflammation and neurodegeneration, two processes closely tied to MS. The study, published in Nature Medicine in August 2016, may point to potential new therapeutic targets, as well as biomarkers for diagnosis and monitoring disease progression.
+ The Parkinson's Disocvery Engine: Understanding Disease Progression
Clemens Scherzer, MD, is working to decode the genetic architecture controlling disease progression in Parkinson’s, which will lay the groundwork for precision therapies, improving clinical trial design and heralding a new era of tailored treatment for Parkinson’s.
In Parkinson’s disease, as in many neurodegenerative conditions, the pace of disease progression varies considerably among patients, but the underlying mechanisms driving these differences remain poorly understood. Clemens Scherzer, MD, is working to decode the genetic architecture controlling disease progression in Parkinson’s, which will lay the groundwork for precision therapies, improving clinical trial design and heralding a new era of tailored treatment for Parkinson’s. Dr. Scherzer is working to develop genetic biomarkers that are predictive of how the disease will progress, and he is partnering with pharmaceutical companies to match drugs to the specific targets identified by these markers. More aggressive inherited forms of the disease can be blocked, and mutations that slow or halt the progression of Parkinson’s—protective genes—will be targets for drugs that aim to mimic that effect. The goal is to speed potential new therapies to clinical trial and, ultimately, prevent disease progression.
+ Unraveling the Mysteries of Neurologic Disease in Women
Evidence-based studies are being conducted to improve how we care for pregnant women with MS and their babies. Research will center on several critical areas, including identifying the underlying biological mechanisms behind the different risk profiles of women and men, as well as the most significant gaps in our understanding and how to best capitalize on this emerging understanding to develop treatments and services specifically for women.
Although sex differences are pervasive in neurologic diseases, they represent an underserved area of research where many key questions remain unanswered. Researchers at the center aim to help fill this critical knowledge gap through an exciting new focus that will build upon research already underway by our expert investigators. This new effort is a response to the unique challenges faced by women, who often find themselves at the intersection of patient and caregiver. For example, the new PREG-MS study led by Maria Houtchens, MD, aims to create the first evidence-based guidelines to improve how we care for pregnant women with MS and their babies. Research will center on several critical areas, including identifying the underlying biological mechanisms behind the different risk profiles of women and men, as well as the most significant gaps in our understanding and how to best capitalize on this emerging understanding to develop treatments and services specifically for women. Center investigators will collaborate closely with expert colleagues from across BWH and beyond, harnessing a wealth of multidisciplinary expertise and advancing a comprehensive approach to these complex issues.
+ New Frontiers in Brain Imaging
Research teams will have access to state of-the-art imaging technologies, including a 7 Tesla (7.0T) MRI scanner, the newest and most powerful MRI machine available and the first to be installed in a clinical setting in North America, which will allow clinicians and researchers to visualize structures and pathways not previously visible by MRI.
With the opening of the Building for Transformative Medicine, clinicians and researchers at the center now have access to advanced tools and opportunities to collaborate, pushing the boundaries of discovery in ways that have never been possible before. Research teams will be able to leverage state of-the-art imaging technologies, including a 7 Tesla (7.0T) MRI scanner, the newest and most powerful MRI machine available and the first to be installed in a clinical setting in North America. Due to arrive in 2017, the 7.0T will allow clinicians and researchers to visualize structures and pathways not previously visible by MRI, offering new insight into otherwise unseen processes. The vastly improved signal will help differentiate between conditions with similar symptoms and allow doctors to choose the best treatment options for patients. The 7.0T will at first be used exclusively for clinical research, with the hope that it will soon be approved by the FDA for clinical use. A true game changer, this new instrument will help our research teams to propel work forward across all five disease areas, paving the way toward a new era in diagnosis, monitoring, and treatment for neurologic diseases.