[Parkinson's] Safety and Delay of Disease Progression Following Administration of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Multiple System Atrophy

Study Summary

Study Results

Eleven of 29 patients with multiple system atrophy were administered mesenchymal stem cells cultured from their own bone marrow, and their outcomes were compared with those of the remaining 18 patients over a 12-month period. The primary outcome measure was the change in the Unified Multiple System Atrophy Rating Scale (UMSARS; higher scores indicate more severe symptoms).

The UMSARS score in the treatment group remained lower than the baseline throughout the 12-month period, whereas the control group’s score increased by an average of 14.7 points (±10.4) at 12 months. A difference between the two groups was observed at every follow-up visit (P = 0.002 at 12 months). The treatment group also showed favorable results in items related to orthostatic symptoms and cerebellar function. PET scans revealed that 5 patients in the treatment group had increased glucose metabolism in the cerebellum and white matter, while 10 patients in the control group had decreased glucose metabolism in the cerebellum and brainstem.

Fever developed in 6 patients (54.5%) following intravenous administration but subsided within 1 to 3 hours with antipyretics. On MRI the day after arterial administration, focal lesions smaller than 5 mm were observed in 7 patients (63.6%), and there were no neurological symptoms. No delayed adverse reactions were observed over the 12-month period.

Figure. Changes in UMSARS scores between the treatment and control groups

Study Design

This was an open-label study conducted at a single tertiary general hospital in Korea, in which patients with multiple system atrophy were randomized using a randomization table into a treatment group and a control group. Of the 29 total participants, 11 were in the treatment group and 18 in the control group; the control group received neither cell therapy nor a placebo procedure. At the 12-month mark, 11 participants remained in the treatment group and 15 in the control group.

Evaluations were conducted at 2-month intervals for 12 months, starting from the baseline. The UMSARS consists of 12 items for medical history, 14 items for motor examination, autonomic nervous system examination, and a global disability scale; the average of scores from two independent evaluators was used. Five participants in the treatment group and 10 in the control group also underwent PET scans.

Cells Used and Administration Method

Autologous bone marrow-derived mesenchymal stem cells obtained from the patients’ own bone marrow were used. Five milliliters of bone marrow were collected from the posterior iliac crest and cultured in a GMP facility to yield 1×10⁸ cells per patient. The cultured cells were at least 93% SH-antigen-positive and CD34- and CD45-negative, with a viability rate of at least 95% and no microbial contamination.

First, a catheter was inserted into the right femoral artery, and 2×10⁷ cells were administered to each internal carotid artery and 2×10⁷ cells to the dominant vertebral artery over a period of 60 minutes. Starting one month later, 4×10⁷ cells were administered via a vein in the arm once a month for three months over a period of 30 minutes, resulting in a total of 16×10⁷ cells per patient.

Discussion

This study demonstrates that patients with multiple system atrophy who received autologous bone marrow-derived mesenchymal stem cells via arterial and venous administration showed less deterioration in UMSARS scores over 12 months compared to the control group. The 14.7-point increase in the control group is similar to the 17.2 points reported by the European Multisystem Atrophy Study Group.

The researchers noted that, given the improvement in cerebellar function-related items and increased cerebellar metabolism in the treatment group, it is difficult to explain the observed changes solely by a placebo effect. The mechanism of action has not yet been elucidated.

There are also clear limitations. The sample size was small (29 participants), and because it was an open-label study without blinding, a placebo effect may have been present. The baseline UMSARS score in the treatment group was 71.6 points, higher than the 39.1 points in the control group, and the duration of the disease was also longer. The researchers stated that further randomized, placebo-controlled trials are needed. The cells were manufactured at Pamicell’s GMP facility, and the study was funded by the Ministry of Health and Welfare.