Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Intrathecal Autologous Mesenchymal Stem Cells in Multiple System Atrophy – Finding the Optimal Dose
Neuromuscular and Clinical Neurophysiology (EMG)
P5 - Poster Session 5 (8:00 AM-9:00 AM)
1-005
To explore an intermediate add-on dose-cohort to a phase I/II study of intrathecal autologous mesenchymal stem cells (MSCs) in multiple system atrophy (MSA).
We recently completed a dose-escalation trial of intrathecal MSCs, which established safety and compelling efficacy signals with a dose of 50x106 MSCs per injection. However, MRI showed changes of the cauda equina, and a number of patients reported low-back discomfort. A dose of 10x106 showed no side effects but a lower efficacy signal.
We enrolled additional patients with confirmed MSA to receive intrathecal injections of 25x106 MSCs at baseline and 6 months. Patients were followed for 12 months with clinical, laboratory, and MRI surveillance. Primary endpoints were frequency and type of adverse events; secondary endpoints were the rate of clinical progression (Unified MSA Rating Scale, UMSARS) and surrogate efficacy measures with neurotrophic factors and neurofilament light chain (NFL) in CSF, and MRI morphometry. We compared outcomes with those of a simultaneously conducted natural history biomarker study.
All 6 enrolled patients had MSA-C. One patient reported transient mild low back discomfort indistinguishable from soreness from lumbar puncture. MRI showed very subtle changes of the cauda equina in two patients. The clinical rate of change measured by UMSARS was close to zero. There was a significant rise in neurotrophic factors following injections. While in our natural history cohort NFL did not change measurably over a 1-year period, there was significant decline of NFL in all MSC-treated patients. In contrast to measurable progression of atrophy in cerebellum and brainstem in the natural history cohort, MSC-treated patients showed minimal to no progression.
A dose of 25x106 MSCs was very well tolerated and associated with remarkably minimal disease progression with highly consistent findings in clinical, laboratory, and imaging measures. The findings establish this dose as the optimal dose for future efficacy trials.
Authors/Disclosures
Wolfgang Singer, MD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic)
PRESENTER 		Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. The institution of Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Yoda. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ferrer. The institution of Dr. Singer has received research support from NIH. The institution of Dr. Singer has received research support from FDA. The institution of Dr. Singer has received research support from Michael J. Fox Foundation. Dr. Singer has received intellectual property interests from a discovery or technology relating to health care.
Allan Dietz No disclosure on file
No disclosure on file
Ann M. Schmeichel Ann M. Schmeichel has nothing to disclose.
Prashanthi Vemuri, PhD (Mayo Clinic) The institution of Dr. Vemuri has received research support from NIH.
Anna Castillo Anna Castillo has nothing to disclose.
Tonette Gehrking Tonette Gehrking has nothing to disclose.
No disclosure on file
Jade Gehrking (Mayo Clinic, Neurology Dept) Jade Gehrking has nothing to disclose.
Elizabeth A. Coon, MD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic) Dr. Coon has received publishing royalties from a publication relating to health care. Dr. Coon has a non-compensated relationship as a Non-Voting Member of the Board of Directors with UCNS that is relevant to Â鶹´«Ã½Ó³»­ interests or activities.
Paola Sandroni, MD, PhD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic) Dr. Sandroni has nothing to disclose.
Phillip A. Low, MD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic) Dr. Low has nothing to disclose.