Cindy Yang, United States of America
Alkahest ResearchAuthor Of 1 Presentation
EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE
Abstract
Aims
As the world’s aging population is steadily increasing, novel therapeutics targeting age-related diseases such as Alzheimer’s disease (AD) are of essential and immediate concern. We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. GRF6019 has advanced to clinical testing in AD, and GRF6021 is a related plasma fraction that improves cognition, increases neurogenesis and neuronal activity, and dampens neuroinflammation in aged mice. Here, we determined whether GRF6021 could impact AD-specific neuropathology and functional deficits in P301S mutant human tau transgenic mice.
Methods
Six-month-old mice overexpressing human P301S tau were treated with GRF6021. Connectivity and functional brain activity were assessed with functional ultrasound, and cognitive function with behavioral testing. Histology and biochemistry were performed to determine the progression of neuroinflammation and tau pathology.
Results
Transgenic mice exhibited a severe deficit in neuronal activity that was fully rescued with treatment of GRF6021. GRF6021 treatment improved contextual memory in transgenic mice in a fear conditioning paradigm, and histological analysis showed that GRF6021 may induce these benefits by reducing neuroinflammation and tau pathology in the brain.
Conclusions
GRF6021 provides an innovative strategy to modulate multiple parallel mechanisms relevant for aging and AD biology. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD.