ENGINEERING THE IMMUNE SYSTEM TO COMBAT NEURODEGENERATION
Excessive neuroinflammation amplifies neurodegenerative diseases, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s disease, Progressive Supranuclear Palsy, Frontotemporal Dementia (FTD), and Multiple Sclerosis (MS).
Regulatory T cells (Tregs) are a T lymphocyte subpopulation that maintain homeostasis in the immune system, mediate immune tolerance, and suppress activities of other immune cells. As such, Tregs are an ideal cell for immune-engineering methods to combat neurodegeneration.
The immunomodulatory effects of Tregs have been widely investigated in central nervous system (CNS) disorders, and have been shown to confer protection in models of Alzheimer’s disease, ALS, stroke, Parkinson’s disease, and MS and related pathologies. Further, a Phase 1 clinical trial demonstrated that autologous (the patient’s own) Treg infusions reduce disease progression in ALS patients, however, autologous Tregs target the CNS inefficiently and also require frequent and large infusions to induce a therapeutic effect. Further, patients with many of these conditions have Treg abnormalities, reducing the efficacy of an autologous approach.
AZTherapies is pioneering an allogeneic (non-self) CAR-Treg platform that aims to:
We are currently validating our cell therapy platform in human in vitro assays and in vivo models of neurodegenerative diseases, with initial proof-of-concept expected to read out in mid-2020. (See Pipeline for more on the clinical development of our CAR-Treg platform)
Source: Hu, X et al., 2018, Nature Reviews | Neurology, Macmillan Publishers Limited