Abstract Details

Title Long-term Administration of Intrathecal Mesenchymal Stem Cells in Multiple System Atrophy – A Compassionate Use Experience

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S18 - Autonomic Disorders (4:03 PM-4:14 PM)

Poster/Presentation
Number 004

Background We recently completed a phase I/II dose-escalation study of intrathecally administered autologous, adipose-derived MSCs in MSA. The study showed a favorable safety-profile and treatments were well tolerated up to a dose of 5 x 10⁷ cells per injection. There were compelling clinical and biomarker efficacy signals supporting continued exploration of this approach.

Objective

To explore the long-term safety of repeated intrathecal administration of autologous mesenchymal stem cells (MSCs) as therapeutic approach to multiple system atrophy (MSA).

Design/Methods Patients who completed the original phase I/II study were invited to receive additional intrathecal MSC administrations of 5 x 10⁷ cells per injection every 6 months. Exclusion criteria included faster than expected disease progression and an advanced disease stage unlikely to benefit from this compassionate extension. Patients were followed with serial clinical, laboratory, and MRI surveillance. Primary endpoints were frequency and type of adverse events (AEs); secondary endpoints included measures of disease progression (Unified MSA Rating Scale, UMSARS).

Results Of 16 patients invited for this study extension all chose to participate. The protocol is ongoing and patients have received up to 7 additional injections. Repeated injections have shown a similarly favorable AE profile as the original trial. Main AEs continue to be abnormalities on MRI imaging of the cauda equina and self-limited low back discomfort, in none of the patients troublesome enough to decline further treatments. The observed rate of disease progression in the first year of this extension study (UMSARS Total 43.4±12.6 at baseline vs. 48.3±14.2 at 12 months) remained slower than expected, but the efficacy signal seemed weaker as the disease progressed.

Conclusions

Repeated, long-term intrathecal MSC administration in MSA is safe and well tolerated. The efficacy signal observed at early disease stages continues to be seen but seems to decline at later disease stages.

Authors/Disclosures
Wolfgang Singer, MD, FAAN (Mayo Clinic) PRESENTER	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UniQure. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. 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
Tonette Gehrking	Tonette Gehrking has nothing to disclose.
	No disclosure on file
David M. Sletten, MBA (Mayo Clinic)	Mr. Sletten has nothing to disclose.
Jade Gehrking (Mayo Clinic, Neurology Dept)	Jade Gehrking has nothing to disclose.
Elizabeth A. Coon, MD, FAAN (Mayo Clinic)	Dr. Coon has nothing to disclose.
Paola Sandroni, MD, PhD, FAAN (Mayo Clinic)	Dr. Sandroni has nothing to disclose.
Eduardo E. Benarroch, MD, FAAN (Mayo Clinic)	Dr. Benarroch has nothing to disclose.
James H. Bower, MD, MSc, FAAN (Mayo Clinic)	The institution of Dr. Bower has received research support from Abbvie.
Anhar Hassan, MBBCH, FRACP, FRCPI, FAAN (Beaumont Hospital)	The institution of Dr. Hassan has received research support from Intrabio . Dr. Hassan has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with Korean Movement Disorders Society.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Ann M. Schmeichel	Ann M. Schmeichel has nothing to disclose.
Karla Minota, MD	No disclosure on file
Phillip A. Low, MD, FAAN (Mayo Clinic)	Dr. Low has nothing to disclose.

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