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

Sara Fernández-Guinea, Mercedes Zurita, Jorge Mucientes, Estefanía García-Zamora, Mario A. Parra, Jesús Vaquero

Research output: Contribution to conferencePoster

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.

Conference

ConferenceAlzheimer's Association International Conference
CountryUnited States
CityLos Angeles
Period14/07/1918/07/19

Fingerprint

Stromal Cells
Cell- and Tissue-Based Therapy
Short-Term Memory
Alzheimer Disease
Mesenchymal Stromal Cells
Glucose
Amyloid Plaques
Fluorodeoxyglucose F18
Brain
Therapeutics
Neuroimaging
Color
Stroke

Keywords

  • Alzheimer's disease
  • short-term memory binding
  • intrathecal cell therapy

Cite this

Fernández-Guinea, S., Zurita, M., Mucientes, J., García-Zamora, E., Parra, M. A., & Vaquero, J. (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. Poster session presented at Alzheimer's Association International Conference, Los Angeles, United States.
Fernández-Guinea, Sara ; Zurita, Mercedes ; Mucientes, Jorge ; García-Zamora, Estefanía ; Parra, Mario A. ; Vaquero, Jesús. / Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases. Poster session presented at Alzheimer's Association International Conference, Los Angeles, United States.1 p.
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title = "Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases",
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.",
keywords = "Alzheimer's disease, short-term memory binding, intrathecal cell therapy",
author = "Sara Fern{\'a}ndez-Guinea and Mercedes Zurita and Jorge Mucientes and Estefan{\'i}a Garc{\'i}a-Zamora and Parra, {Mario A.} and Jes{\'u}s Vaquero",
year = "2019",
month = "7",
day = "14",
language = "English",
note = "Alzheimer's Association International Conference ; Conference date: 14-07-2019 Through 18-07-2019",

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Fernández-Guinea, S, Zurita, M, Mucientes, J, García-Zamora, E, Parra, MA & Vaquero, J 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' Alzheimer's Association International Conference, Los Angeles, United States, 14/07/19 - 18/07/19, .

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; Zurita, Mercedes ; Mucientes, Jorge ; García-Zamora, Estefanía; Parra, Mario A.; Vaquero, Jesús.

2019. Poster session presented at Alzheimer's Association International Conference, Los Angeles, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases

AU - Fernández-Guinea, Sara

AU - Zurita, Mercedes

AU - Mucientes, Jorge

AU - García-Zamora, Estefanía

AU - Parra, Mario A.

AU - Vaquero, Jesús

PY - 2019/7/14

Y1 - 2019/7/14

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - short-term memory binding

KW - intrathecal cell therapy

M3 - Poster

ER -

Fernández-Guinea S, Zurita M, Mucientes J, García-Zamora E, Parra MA, Vaquero J. Preliminary evidence of the impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer’s disease cases. 2019. Poster session presented at Alzheimer's Association International Conference, Los Angeles, United States.