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Abstract Details

A Futility Trial of Sirolimus in Multiple System Atrophy: Protocol, Recruitment and Preliminary Adverse Event Profile
Movement Disorders
P3 - Poster Session 3 (5:30 PM-6:30 PM)
10-019

We present the protocol, recruitment numbers, and preliminary adverse event profile of patients with multiple system atrophy (MSA) enrolled in a single-center, NIH-funded futility trial with sirolimus (NCT03589976).
In patients with MSA, autophagy is impaired and misfolded αSyn accumulates in neurons and glia, causing neurodegeneration. Sirolimus, a medication that has been approved by the U.S. Food and Drug Administration for chronic treatment in humans for a variety of disorders for almost 20 years ago, is a potent activator of autophagy. We hypothesize that treatment with sirolimus might activate autophagy of αSyn resulting in reduced neurodegeneration and slower progression of the neurological deficits in patients with MSA.
Single-center, randomized, placebo-controlled, phase-2 futility clinical trial to determine if sirolimus is of sufficient promise to slow the disease progression of patients with MSA, prior to embarking on a large-scale and costly phase-3 study to assess its efficacy. Non-futility will offer strong support for a phase-3 trial to detect clinical efficacy. We will enroll 56 patients with a 3:1 (sirolimus:placebo) randomization. We expect to complete enrollment within 2 years.
The first patient was screened and enrolled in September 2018. By October 2018, 10 patients have been screened and 7 have been enrolled. By April 2019 we expect to have enrolled 25 patients (44% of our final target enrolment). By October 2018, 3 patients have been randomized. No adverse events have been reported so far. Recruitment and adverse events will be updated by the time of this abstract presentation.
This is the first time sirolimus or analogs will be used clinically with the aim of slowing disease progression in patients with neurodegenerative disorders. Our observations may offer strong support for a phase-3 trial to confirm the efficacy of sirolimus in MSA. 
Authors/Disclosures
Jose-Alberto Palma, MD, PhD, FAAN (New York University Grossman School of Medicine)
PRESENTER 		Dr. Palma has received personal compensation for serving as an employee of Eli Lilly. The institution of Dr. Palma has received research support from National Institutes of Health. Dr. Palma has received publishing royalties from a publication relating to health care.
No disclosure on file
Erin Barnes, MD (Albany Medical Center) An immediate family member of Dr. Barnes has received personal compensation for serving as an employee of Go2For Lung Cancer. The institution of Dr. Barnes has received research support from NIH.
Sharon S. Simon (University of Sao Paulo Medical School) No disclosure on file
No disclosure on file
Horacio C. Kaufmann, MD, FAAN (NYU Langone Health - NYU Dysautonomia Center) Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Therapeutics. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AskBio. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BioArctic. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Spinger. The institution of Dr. Kaufmann has received research support from Biogen. The institution of Dr. Kaufmann has received research support from Vaxxinity. Dr. Kaufmann has received publishing royalties from a publication relating to health care.