Description:
Reference #: 01427
The University of South Carolina is offering licensing opportunities for TGFbeta1 hyperactivation causes gender-specific calcific aortic stenosis
Background:
Calcific aortic valve disease (CAVD) affects 25% of the population over 65 years of age. The CAVD is a progressive disease ranging from aortic valve (AoV) sclerosis, which is the stiffening of the heart valves being replaced with scar tissue, to AoV stenosis (AS) which is the narrowing of heart valves. In the first phase of the disease, termed aortic sclerosis, the valve becomes thickened and mildly calcified, but these changes do not cause any obstruction to blood flow. Over the years, the disease evolves to severe valve calcification and thickening with impaired leaflet motion and significant blood flow obstruction, which are hallmarks of calcific AS. In developed countries, AS has a prevalence of 0.4% in the general population and 1.7% in the population greater than 65 years old. Congenital abnormality (structural abnormalities of the heart), male gender, and older age are powerful risk factors for calcific AS. There is no medical treatment for the CAVD. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe calcific AS. The developmental, cellular, molecular, and biochemical mechanisms involved in the development and progression of CAVD remain poorly understood.
Invention Description:
We identified novel developmental, cellular, molecular, and biochemical pathways and developed a unique mouse model that recapitulates age, bicuspid aortic valve-associated, and gender-specific pathological aspects of development and progression of human CAVD. Our results have uncovered novel developmental, cellular, molecular, biochemical pathways and approaches for therapeutic targeting to block the development and/progression of CAVD in mice. Novel observations are likely to emerge from these findings which will favorably shift the current paradigm and approaches for early detection and prevention and strategies for targeting specific pathways for potential medical treatment of CAVD as well as calcific AS progression in older humans. For the first time, we have developed and established a reliable and convenient adult mouse model that ‘spontaneously’ develop calcific AS. These mice will be useful in developing and testing novel diagnosis, prevention and treatment strategies for the CAVD.
Potential Applications:
This model will be used to test novel small molecule inhibitor compounds, antibodies, ligand-traps which are either commercially available or obtained from industry (via MTA). Successful application will result in further testing of the select compounds in a larger animal model and/or in human safety trials.
Advantages and Benefits:
Currently, there are no mouse models, which could effectively recapitulate age, BAV-associated, and gender-specific development and progression of calcific AS. Overall, these results successfully establish the causative role of TGFβ1 and 3/4 underlying pathogenic mechanisms involved in the development and pathogenesis of CAVD that recapitulates both age and gender-specific etiology associated with calcific AS in humans.