Abstract Details

Title Clinical and Immunologic Safety Evaluation of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 17-011

Objective To evaluate the safety of intravenous (IV) allogeneic bone marrow-derived mesenchymal stem cells (allo-hMSCs) in Parkinson’s disease (PD) across Phase I and Phase II clinical trials.

Background Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, making them a promising therapy for PD. However, safety profiles in PD remain limited, especially regarding repeated infusions and potential antibody-mediated rejection.

Design/Methods

Both trials enrolled participants with mild to moderate PD, aged 45-79, OFF-state Hoehn and Yahr stage £ 3, and 4-10 year disease duration. Phase I (n=20) tested single escalating IV infusions of 1, 3, 6, or 10 x 10⁶MSCs/kg. Phase II (n = 30) administered either three infusions of 10 x 10⁶MSCs/kg or two MSC infusions plus one placebo every 18 weeks. No pre-treatment was used. Adverse events (AEs), HLA profiles, and calculated panel reactive antibody (cPRA) values were recorded at prespecified intervals.

Results Across both trials, 215 AEs were reported; 10 AEs (4.7%) were treatment-related. Of these, 8 were mild, 1 moderate, and 1 severe. Common AEs included dyskinesia (30%), nausea (20%), and lymphocytic changes (20%). The single severe AE was a new diagnosis of chronic lymphocytic leukemia in a participant with pre-existing stable lymphocytosis, which eventually stabilized. Twenty-eight participants (56%) had stable or reduced cPRA values. Transient increases occurred in 8 (16%), and sustained increases with new HLA specificities in 6 (12%), only from Phase II. New HLA specificities emerged in 8 participants (16%) without cPRA changes. Sensitization showed a nonsignificant trend towards higher sustained increase in Phase II (p = 0.09). No donor-specific antibodies were detected.

Conclusions

Single and repeated IV MSC infusions are safe and well tolerated. Although multiple dosing increased the sensitization risk, most participants remained at low cPRA, supporting a favorable safety and immunologic profile for allo-hMSC therapy in PD.

Authors/Disclosures
Chiamaka C. Onuigbo, MD PRESENTER	Dr. Onuigbo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal.
Jerome Saltarrelli, PhD	Dr. Saltarrelli has nothing to disclose.
Juan D. Martinez Lemus, MD (The University of Texas Health Science Center at Houston)	Dr. Martinez Lemus has nothing to disclose.
Emily Tharp, MD	Dr. Tharp has nothing to disclose.
Scott D. Olson, PhD (UT Health)	Dr. Olson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Bryan Cave Leighton Paisner LLP. Dr. Olson has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Smith Gambrell Russell via Teklicon. The institution of Dr. Olson has received research support from HART. The institution of Dr. Olson has received research support from Cellvation. The institution of Dr. Olson has received research support from Hope Bio. Dr. Olson has received intellectual property interests from a discovery or technology relating to health care.
Fabio Triolo, PhD	The institution of Dr. Triolo has received research support from Department of the US Army – USAMRAA.
Joana Bianchi, PhD	Dr. Bianchi has nothing to disclose.
Robert Ritter III	Mr. Ritter has nothing to disclose.
Mya C. Schiess, MD, FAAN (Univ of Texas-Houston Med School)	Dr. Schiess has nothing to disclose.

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