Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases

Fernández-Guinea, Sara and Zurita, Mercedes and Mucientes, Jorge and García-Zamora, Estefanía and Parra, Mario A. and Vaquero, Jesús (2019) Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases. In: Alzheimer's Association International Conference, 2019-07-14 - 2019-07-18, Los Angeles Convention Centre.

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    Abstract

    Background: A decrease in brain glucose metabolism in Alzheimer’s disease (AD) patients is considered a critical driver of cognitive impairment, and medications used in AD target this metabolic dysfunction. Recent evidence has shown a significant increase in glucose metabolism associated with neurocognitive improvement after intrathecal administration of bone marrow mesenchymal stromal cells (MSCs) in patients suffering from severe TBI or haemorrhagic stroke. We hypothesise that this cell therapy could also be useful in AD patients. Methods: We studied two AD patients with cerebral beta-amyloid neuritic plaques detected with 18FFDG-PET. The patients received every three months 100 million of autologous MSCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F-FDG-PET and assessment with the visual short-term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Results: A global increase in cerebral glucose metabolism was observed after each administration of cell therapy. Single case statistics revealed that treated and untreated patients did not differ on their pre-treatment VSTMBT scores and both were significantly impaired relative to controls. The chance that an untreated AD patient would show more impairment than treated patients was 39.25% (p= 0.785) for case 1, and 50.00% (p=1.0) for case 2. This chance increased post-treatment to 97.40% (p=0.05) and 99.74% (p=0.005) respectively. Conclusion: These preliminary findings suggest that intrathecal administration of autologous MSCs should be considered as a new therapeutic strategy for Alzheimer’s dementia and deserves further studies.