TGF Beta Agonists for Neuroprotection and Treatment of Alzheimer's Disease

Prof. Tony Wyss-Coray and colleagues have identified a first-in-class small molecule with the potential for treating Alzheimer's disease and reversing some of its pathology. This compound was discovered due to its agonist effect on TGF-beta (a protein that has been shown to reduce ABeta accumulation in mouse models of Alzhemier's disease). Pre-clinical studies have demonstrated that oral administration of this agent can delay or reduce neurodegeneration and cognitive impairment in a mouse model of Alzheimer's disease. In addition, the molecule provided neuroprotection in a mouse model of neuronal damage.

Stage of Research
The inventors have performed a wide range of pre-clinical studies and are planning to apply for grants to support an IND filing. Studies to date include:

• characterization as orally active drug with minimal toxicity
• testing to verify activation TGF-beta signaling in the CNS
• demonstration of neuroprotective effects in vivo with models of acute neurodegeneration and Alzheimer's disease
• behavioral studies in mice to show the orally administered compound can delay or rescue memory deficits
• large animal toxicology