# Clinical Trial Readiness for Multiple System Atrophy

> **NIH NIH U01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $230,598

## Abstract

SUMMARY/ABSTRACT
The overall aim of this study is to develop and validate sensitive clinical and biological outcome measures for
clinical trials of patients with multiple system atrophy (MSA), a fatally progressive rare neurodegenerative
disorder with no cure. Recent breakthroughs in MSA research have identified the crucial role of misfolded α-
synuclein as disease-causative mechanism and there are finally a number of candidate drugs in the pipeline
aimed at slowing or arresting disease progression. Multiple drug companies are now working toward MSA-
targeted therapies and two placebo-controlled clinical trials are ongoing. However, MSA experts along with
industry and regulatory agencies, have identified several weaknesses in our current clinical trial arsenal, with
the lack of sensitive outcome measures as the main limitation. At present, there is only one clinical rating scale
for MSA (the UMSARS) validated as outcome measure for use in clinical trials. The downside is that the
UMSARS is only moderately responsive to change, so it requires large cohorts of study subjects and a long
follow-up period to achieve sufficient statistical power to test the effect of candidate drugs, which is not ideal for
a rare rapidly progressive disorder. There is also a lack of imaging or biochemical biomarkers to track disease
progression. To reach clinical trial readiness for MSA, we propose an international, multicenter, prospective
observational study enrolling 100 patients with MSA followed for a year at 4 sites. We will leverage the existing
infrastructure of the Natural History Study of the Synucleinopathies (an initiative started within the NIH RDCRN
Autonomic Rare Disorders Clinical Research Consortium), and the European MSA Study Group, both of which
include an established network of highly collaborative academic sites sharing their data. With the support of
three pharmaceutical companies working on disease-modifying candidates for MSA, and the endorsement of
the major MSA advocacy groups, we have a unique opportunity for a tight collaboration of all stakeholders to
jointly address the remaining challenges and establish clinical trial readiness for MSA. Our GOALS are: AIM 1.
To develop a novel clinical outcome assessment (COA) and determine its validity. We will determine the ability
to detect change and the response rate of each item of the UMSARS and other clinical scales from historical
data already collected from 400 patients with MSA who were enrolled in the RDCRN Natural History Study of
the Synucleinopathies. We will remove redundant items or with little ability to detect change, and, with the input
of patient advocacy groups, will develop a new COA, which we will validate prospectively in newly enrolled
MSA patients. AIM 2. To compare the responsiveness of the new COA against the UMSARS and determine
the minimally clinically important difference. AIM 3. To validate neuroimaging and biochemical biomarkers of
disease progression in MSA for their us...

## Key facts

- **NIH application ID:** 10833959
- **Project number:** 3U01NS122419-02S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** HORACIO KAUFMANN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $230,598
- **Award type:** 3
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833959

## Citation

> US National Institutes of Health, RePORTER application 10833959, Clinical Trial Readiness for Multiple System Atrophy (3U01NS122419-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10833959. Licensed CC0.

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