Established twice monthly, our multidisciplinary clinic P+A+MSA Clinic (Parkinson’s + Ataxia + Multiple System Atrophy), is an MSA Center of Excellence. It was founded in 2017 by Dr Khurana. It takes place on the 2nd and 4th Friday of each month. In each clinic session patients are evaluated by three different specialties in consecutive, scheduled appointments. These include a movement disorders specialist (MD, NP, or PA), neuro-physical therapist, and social worker. All appointments take place in the neurology outpatient clinic at the Hale Building for Transformative Medicine in the Brigham and Women’s Hospital Main Campus. On the first Friday of each month, the core team meets to discuss prior and forthcoming cases develop a cohesive plan for diagnosis and treatment. We conduct a battery of clinical and diagnostic investigations (e.g., autonomic function tests, urodynamic studies, UPSIT, DaT/MIBG/PET scans and volumetric MRI).
Additionally, our monthly Movement Genetics Clinic evaluates early-onset MSA patients and those with a family history. This clinic runs on the second and fourth Thursdays of each month. Patients from the Multidisciplinary PAMSA clinic who have relevant family history, or an unusually early presentation are discussed in our BWH Movement Disorders genetics clinic and are seen by a genetics counselor. In this appointment we will determine the need for additional genetic testing as clinically indicated.
We have an active referral base to specialists and allied health professionals including medical and imaging specialists with dedicated clinical and research effort for MSA (see “Clinical Staff” below).
Please ask your movement disorders specialist for more information at your next appointment.
We are actively involved in conventional Biopharma clinical trials (recent enrolments for Biohaven, Teva and Ono), but we are also developing our own therapies for MSA. We have, for example, an IND pending for treating MSA with an anti-CD3 antibody (Foralumab) developed at BWH with clinical trial slated to begin late Fall 2023.
Our MSA patients are all enrolled in a clinical trial-ready cohort program that involves thorough diagnostic testing and longitudinal tracking with biometrics (video oculography, accelerometry, Hevelius computerized app) and biomarkers (Harvard Biomarkers Study and CLIMB study which, together, track more than 4000 patients longitudinally with neurologic disease). Patients are also offered experimental PET tracers (for neuroinflammation, TSPO PBR06, and, through an active collaboration with AC Immune, alpha-synuclein) with > 10 patients scanned with these novel tracers to date.
Dr. Anastasia Kuzkina has helped pioneer the seeded amplification of alpha-synuclein for patients with MSA, PD and related disorders from skin and nasal brushings. This allows us to identify the specific form of alpha-synuclein aggregating in our patients’ brains and to make earlier and more precise diagnoses.
We have assembled at BWH the largest collection worldwide of induced pluripotent stem cells (iPSC) form MSA patients, many of which are matched to postmortem brains. These cells allow us to create patient-specific models of MSA for drug discovery “in the dish”. These iPSC lines are freely available to anyone in the research community. We have begun to test different therapeutic strategies in these models, and hope in time to be able use them to match our patients to the correct treatment. Our aim is to slow down the progression of MSA.
Our clinical center has played a coordinating role in the development of MSA Coalition Core G, with genomes of our patients at BWH being sequenced both by this Core and also with AMP-PD at the NIH (Sonja Scholz, MSA). The aim of this research is to identify genetic risk factors contributing to MSA.
One major challenge for developing therapies for MSA is our inability to identify accurately the accumulation of the protein alpha-synuclein in the brain of MSA patients. Recently, our center with collaborators were winners of the Ken Griffin award from the Michael J. Fox Foundation to develop an alpha-synuclein radiotracer. We are actively enrolling patients now for testing this radiotracer in addition to another tracer available from the company AC Immune, with whom we have an active collaboration. Our hope is that patients who complete this study will proceed to further clinical trials for MSA therapies.
The point of contact for our research program in MSA is Diego Rodriguez, MD (drodriguez29@bwh.harvard.edu).
Our MSA Research is currently supported by the MSA Coalition Seed Grant Program, the Michael J. Fox Foundation, the Barbara Bloom Ranson Fund for MSA Research at Brigham and Women’s Hospital, and the NIH (R01 NS109209).
In a recent manuscript (Ndayisaba et al., Cerebellum 2022) we describe our translational and clinical trials research infrastructure. We are well regarded for our basic research in synucleinopathies and MSA (e.g., Chung, Khurana et al, Science, 2013; Khurana et al., Cell Systems 2017; Vincent et al., Cell Reports 2018; Hallacli et al., Cell, 2022). Our division houses the largest collection of MSA iPSC worldwide, 20 lines of which are matched to human postmortem brain (Ndayisaba, Lam et al., Biorxiv 2022; in revision, Neuron). Dr Kuzkina’s work on the seeded amplification assay for MSA, and related disorders has been described in multiple publications (Kuzkina et al., Movement Disorders 2023; Kuzkina et al., NPJ Parkinson’s Disease 2023; Kuzkina et al., NPJ Parkinson’s Disease 2021).
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