New Rat Model For Autoimmune Therapy Safety/Efficacy
DESCRIPTION (provided by applicant): Autoimmune diseases comprise the third most common category of illness in the United States affecting an estimated 22 million Americans. To date, therapeutic and preventive strategies for human autoimmune diseases (b
ased on the restoration of immune tolerance) have been largely disappointing. Experimental animal models greatly facilitate the study of the pathogenesis and complications of autoimmune disease. They permit the evaluation of treatment protocols that po
se ethical issues and safety risks in humans. They provide populations of genetically identical subjects that can be maintained under controlled environmental conditions. With them, new pharmaceutical agents, dietary regimens etc. can be tested to deter
mine therapeutic benefit while detecting potential toxicity and unanticipated worsening of disease prior to human application. Preclinical testing of new agents and diets therefore represents a multimillion-dollar commercial market that would embrace a n
ew, well-characterized rat model of multiple autoimmune diseases including, especially, T1D and rheumatoid arthritis. In our preliminary studies we report that LEW.1WR1 rats are 1) susceptible to virus-triggered autoimmune diabetes and experimental al
lergic encephalomyelitis, 2) susceptible to adjuvant arthritis, and 3) can develop diabetes during treatment to induce arthritis. These characteristics make the LEW.1WR1 rat an attractive commercial candidate for a test bed for studying both the efficacy
of therapies for autoimmune disease prevention and reversal as well as screening for unanticipated adverse effects that would compromise the safety of such medications. We are therefore requesting funding to enhance the drug-platform-testing utility an
d commercial value of the LEW.1WR1 rat model of autoimmune diseases. In Phase 1 we will fully evaluate the autoimmune susceptibilities of these animals in response to perturbation of innate immunity and viral infection. In Phase 2, we will identify the g
enetic basis of the susceptibility of LEW.1WR1 rats to the different forms of autoimmunity characterized in Phase 1. Our specific aims are: 1: Identify the immunological and viral perturbants that increase the penetrance of disease in the LEW.1WR1 rat
model of type 1 diabetes 2. Establish the LEW.1WR1 rat as a model of rheumatoid arthritis 3. Determine if the diabetic LEW.1WR1 rat develops thyroiditis, celiac disease, adrenal insufficiency, and sialadentis for use as a model of these disorders.
PUBLIC HEALTH RELEVANCE: No preventative or curative therapies have been identified for the multiple autoimmune diseases that affect 22 million Americans. Progress in the development of new therapeutics is hampered by the lack of appropriate anima
l models. We have identified a novel autoimmune-susceptible rat strain that is poised to develop multiple autoimmune syndromes in response to environmental pertubants. This unique model is ideally suited for science-based preclinical safety evaluation that
is needed before new therapies can be tested in humans.
Small Business Information at Submission:
BIOMEDICAL RESEARCH MODELS, INC.
BIOMEDICAL RESEARCH MODELS, INC. 67 MILLBROOK, ST, STE 422 WORCESTER, MA -
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