The overall objective of this proposal is further investigate the dopamine (DA) D1 positive allosteric modulator (PAM),, DETQ, in relation to cognitive impairment (CI) of aging in hD1KI mice. DETQ has been shown to be effective in ameliorating CI in preclinical studies. There is considerable evidence that a D1 PAM, alone or in combination with a cholinesterase inhibitor, e.g rivastigmine, or the competitive NMDAR antagonist, memantine, may be useful to treat age- related deficits in cognition and social interaction and even prevent aging- related deficits. Data from the proposed studies will provide new knowledge about the mechanisms underlying DETQ- mediated amelioration of the effects of aging and may be relevant to planning studies of DETQ or equivalent Lilly compounds for Mild Cognitive Impairment (MCI) of aging humans. LY3154207, another D1 PAM Effects is in development for the dementia of Parkinson’s disease (PD). MCI is often far more severe than the name impliesand has great consequences for the affected individuals and society . The proposed studies could also identify additional opportunities for a D1PAM to treat other disorders associated with cognitive decline, e.g. dementias such as Alzheimer’s (AD) and Lewy Body Dementia(LBD) .
|Effective start/end date||11/19/19 → 11/19/21|
- Eli Lilly and Company (Prot #IS00001818)