Treatment of Spinocerebellar Ataxia with Mesenchymal Stem Cells: A Phase I/IIa Clinical Study

Abstract

Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 10 6 cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

“…The use of ADSCs in treating neurological disorders is relatively limited. Less than 10% of current ADSC clinical trials are targeting refractory neurological disorders [16][17][18] such as spinal cord injury, stroke, dementia, and various neurodegenerative disorders. Ideally, these diseases could be treated using human neural stem cells (NSCs).…”

Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease

“…However, recent reports suggest that many patients regress to the status prior to treatment. [23][24][25][26] For maximum success in clinics, it is urgent to understand what has gone wrong regarding MSC therapies.…”

Mesenchymal stem cells prolong survival and prevent lethal complications in a porcine model of fulminant liver failure

“…Human adipose‐derived MSCs were purchased from Steminent Biotherapeutics Inc. Isolation, purification, and culture expansion of these MSCs have been reported previously . Adipose‐derived MSCs were packaged in a cryopreservation bag, and quality certification including surface‐positive immune phenotyping for CD73, CD90, and CD105 and negative for CD34, CD45, CD11b, CD19, and HLA‐DR was carried out.…”

“…Isolation, purification, and culture expansion of these MSCs have been reported previously. 37 Adipose-derived MSCs were packaged in a cryopreservation bag, and quality certification including surface-positive immune phenotyping for CD73, CD90, and CD105 and negative for CD34, CD45, CD11b, CD19, and HLA-DR was carried out. Tri-lineage differentiation capacity into osteogenic, chondrogenic, and adipogenic progenies was also confirmed.…”