By Prof. Dr. Gregor K. Wenning, MD, PhD

MSA Diagnostic Criteria Revision

A major effort to revise the diagnostic criteria for multiple system atrophy is nearing completion. A taskforce was convened to consider deficiencies in the current criteria which had not been revised since 2008. The global community of movement disorder specialist neurologists had the opportunity to give their input in a survey with 470 replies received from 78 countries. The final consensus conference chaired by myself and Dr. Horacio Kaufmann was held virtually April 30 and May 1. The next step is for the writing committee to draft a paper to be submitted for publication in the Movement Disorders Journal this summer. Once published, the new criteria will provide a clear blueprint for neurology practitioners to diagnose MSA with more certainty. It will also help it to be recognized earlier so that patients may be considered in clinical research trials.

Update on MSA Coalition Research Program

The MSA Coalition issued a request for research grant applications that were due in mid-April. A total of 21 short research proposals (letters of intent) have been received and are currently under review by the Scientific Advisory Board (SAB). Nearly $1 Million in funding is being requested for these 1-year “SEED” projects. Those judged most promising will be invited to submit a more detailed project plan which will undergo further review over the summer. Seed grants allow researchers to perform small studies to test a hypothesis and gather more data before applying to government sponsored programs for larger multi-year funding support. The role of the SAB is to advise the MSA Coalition Board of Directors on the scientific relevance of proposed projects. The Board of Directors makes the final funding decisions. The seed grant program has been very successful with 42 projects funded since 2013 for a total of $2 Million.

In recent years the MSA Coalition has begun to develop a “CORE” research program as a complement to their successful seed grant program. Core grants are given to more robust collaborative multi-year projects that will help answer key questions about the disease. The “Core G – Genomics” project is now underway and is being coordinated by Dr. Dana Vuzman who will make use of the Clinical Genome Analysis Platform developed at Harvard Medical School. Although we know that MSA is not typically passed from parent to child there are actually clues that scientists can look for in the genetic makeup of those who develop MSA versus those who do not. A large genetic dataset with many thousands of MSA cases is needed however. Because MSA is a rare disease only small collections of isolated genetic samples are available around the globe. The MSA Coalition recognized that research groups were not working together in an organized fashion to combine their data and from that realization the Core G project was conceived. This project brings together a group of global collaborators who all agree to share their data as they look for common genetic traits in a centralized MSA genetic database which will contain thousands of samples. Dr. Vuzman and colleagues are currently working on building the needed infrastructure to enable the data to be collected and queried.

A second core project, “Core E – Environmental factors” is being overseen by epidemiologist Dr. Beate Ritz at UCLA and will look into environmental and genetic risk factors for MSA. This project is being conducted in collaboration with two established studies in Parkinson’s disease at UCLA. Since we know that MSA is most often misdiagnosed as Parkinson’s disease, this project is proposing to create an algorithm for more accurate identification of patients with MSA from Electronic Health Records. These patients can be contacted in future studies to better understand MSA onset, health care needs, and progression. A second component of this project aims to identify and collect pilot data from patients with MSA in a community heavily exposed to pesticides in the San Joaquin Valley in California. For this effort, neurologists are being contacted to identify and enroll people with MSA (as well as healthy control subjects) for interviews and collection of saliva and stool samples.

International MSA Congress 2021

For two days in late February, the 7th International MSA Congress was hosted virtually by Professor Shoji Tsuji at the University of Tokyo. Normally a much anticipated in-person event, this meeting takes place every 2-3 years and gives scientists with special interest in MSA the opportunity to network and update each other on the latest findings as well as educate young scientists and medical professionals about MSA. Although it was forced to be held virtually due to Covid-19, this year’s meeting was organized in a hybrid model to allow for a combination of livestreamed lectures (including very lively Q&A sessions) as well as on-demand presentations and poster sessions. The meeting was well attended by a global audience and has grown considerably over the last decade, due in large part to the support of the MSA Coalition. This year it was noted that well over a dozen speakers or poster presenters had received past support from the MSA Coalition through their research grant program allowing them to carry out and report on much needed studies. As an outcome of this meeting a special supplementary issue of the journal Cerebellum is being planned for publication later this year.

Clinical Trial Update

The MSA Coalition receives a lot of inquiries about ongoing or upcoming clinical trials. The Verdiperstat trial is still in phase 3 but no longer accepting any new patients. It’s important to remember that until every person enrolled has completed their trial no results good or bad are made available either to the drug company, the study investigators or to the public. We understand some patients may be sharing their impressions, however it is important to note that this is a double blind study. New phase 2 trials for ATH434 and Anle138b are currently being planned. Nothing can be announced until the drug companies make these details public. The phase 3 trial of Ampreloxetine (Sequoia study) for the treatment of neurogenic orthostatic hypotension symptoms commonly experienced by those with MSA is still accepting new patients. More details about these and other trials are available on the MSA Coalition’s treatment pipeline page.

Prof. Gregor K. Wenning, MD, PhD is a movement disorder specialist neurologist and a neurobiologist credited with generating the very first MSA mouse model during his PhD studies at the University of London. He is also the editor of the only medical textbook on Multiple System Atrophy. Prof. Wenning is the director of the Dysautonomia Center and chair of the Division for Clinical Neurobiology at Innsbruck Medical University, Innsbruck, Austria. He serves as chair of the Movement Disorder Society MSA Study Group (MoDiMSA) and is co-founder of the European MSA Study Group. He leads a consortium of 28 MSA centers in Europe and Israel, with the goal of driving forward accurate diagnostic markers and translational therapy research. Combining clinical and basic research, Prof. Wenning’s goal is to find a cure for people affected by multiple system atrophy. He has served on the MSA Coalition’s Scientific Advisory Board since 2012 and as chair since 2019.