Abstract

AbstractBackgroundStem cell therapy has emerged as a promising treatment for neurodegenerative diseases caused by the accumulation of abnormal proteins. We have administered repeated infusions of autologous adipose‐derived stem cells (ADSCs) to 39 patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), Parkinson's disease (PD), multisystem atrophy (MSA) (including spinocerebellar degeneration (SCD)), and Alzheimer's disease. A total of 182 infusions have been administered, and not a single side effect has been observed. In this study, we evaluated cognitive function in 9 patients with cognitive impairment after administration.MethodThis treatment was conducted after registration with the Japanese Ministry of Health, Labour and Welfare, with the consent of the patient, approval of the Ethics Committee, and approval of the Specific Review Board for Regenerative Medicine. Stem cells were harvested from the patient's own abdominal subcutaneous adipose tissue and cultured in serum‐free medium. 5.0x10^7 to 1.2x10^8 stem cells were administered intravenously 5 or 6 times at approximately a‐month intervals. The evaluation was performed by neurologist's examinations, caregiver's interview and Montreal cognitive assessment (MoCA). Amyloid PET scans were performed before and after the treatment in three patients with Alzheimer's disease.ResultMoCA scores averaged 10.3 points before administration and 19.6 points after 5 infusions of ADSC, and there were no cases of deterioration among the 9 patients evaluated. Not only did the overall score improve, but the clock drawing visibly improved. Improvement was also observed in medical examinations and caregiver interviews. Amyloid PET scan in one case showed a decrease in brain amyloid deposition. Three patients had associated parkinsonism but showed significant improvement when assessed by Unified Prkinson's Disease Rating Scale (UPDRS). We confirmed that the administered stem cells were CD10 (neprilysin, an amyloid‐degrading enzyme) positive.ConclusionImprovement in cognitive function was observed after 5 doses of ADSCs infusion. No side effects were observed, confirming that this treatment is repeatable and safe. The mechanism may be amyloid removal by neprilysin, but since parkinsonism is also improved, multiple factors are considered, including neuronal regeneration and repair, improvement of blood flow, anti‐inflammatory effects, and removal of multiple abnormal proteins and deposits, such as alpha‐synuclein in Parkinson's disease.

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