Congratulations to Vivian / Thuy-­Vi Nguyen! NIA R21 grant application that received a 6 percentile

National Institute of Aging Exploratory/Developmental Research Grant Program (Parent R21;; PA-­18-­489) PI: Vivian / Thuy-­Vi Nguyen 


Title: A small molecule p75NTR ligand to treat post-­stroke mixed dementia 

Mixed dementia is a complex form of dementia in which heterogeneous disease states co-­exist, the most common being pathologic characteristics of vascular dementia (VaD), such as chronic stroke infarcts, alongside pathologic characteristics of Alzheimer’s disease (AD). It is unknown precisely how many patients presently diagnosed with a particular type of dementia actually have mixed dementia, however post-­mortem analyses suggest that the condition may be present in nearly 50% of patients clinically diagnosed with AD. Yet despite the frequent co-­existence of VaD and AD, little is known about how these diseases influence each other, in part due to the lack of adequate animal models of mixed dementia, and there are no proven disease modifying therapies. 

To address this need, the goal of this proposal is to test if a first-­in-­class small molecule, orally bioavailable p75 neurotrophin receptor (p75NTR) ligand, LM11A-­31, currently in Phase IIa clinical trials for the treatment of AD, also has efficacy in two different mouse models of post-­stroke mixed dementia. The first, is an innovative model of post-­stroke mixed dementia in which in the weeks following stroke, aged wildtype (wt) mice exhibit cholinergic neurodegeneration along with the appearance of neuritic plaques resembling those found in AD (Aim 1).  The  second,  is  a  transgenic  mouse  model  of  mixed  dementia  in  which  aged  AbbPPL/S  mice  that  have  undergone a stroke develop more severe AD pathology than their age-­matched counterparts (Aim 2). In both of these  models,  mice  also  develop  delayed  cognitive  impairments  in  the  weeks  after  stroke.  Positive  results  obtained here would be the first validation that p75NTR is an effective therapeutic target in two post-­stroke mixed dementia models, and could fast-­track LM11A-­31 into post-­stroke mixed dementia clinical testing. 


Release Date: 
10/25/2018 - 11:15am