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Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
Tetrahydrobiopterin Improves Cardiac Diastolic Relaxation: A New Therapy for Diastolic Dysfunction
(VA 06-032)
OPPORTUNITY
The VA is seeking CRADA and/or licensing partners to commercialize this technology.
TECHNOLOGY BACKGROUND AND DESCRIPTION
A large number of HF patients exhibit a relatively normal ejection fraction concomitant with diastolic dysfunction (DD) which is the impairment of the ventricles to relax normally. This diminution of ventricular relaxation in diastolic HF patients leads to increased ventricular pressure making it harder for all of the blood to go into the ventricle with each heartbeat. Currently, there is no efficacious treatment which slows the progression or reverses DD associated with diastolic HF. The inventors developed an animal model that allowed them test the "redox hypothesis of disease" as it relates to DD. In this hypothesis, a reduction in the vascular availability of nitric oxide (NO) along with an increased production of reactive oxygen species (ROS) is responsible for the initiation and/or progression of DD. The endocardial NO levels are dependent on the expression of endothelial nitric oxide synthase (eNOS), and BH4 is an eNOS co-factor which, along with NO, is subject to oxidative depletion or destruction by excess ROS production. Using their animal model, the inventors successfully demonstrated that dietary supplementation with BH4 improved diastolic function in an eNOS-dependent fashion.
Heart failure (HF) is a progressively disabling and ultimately fatal disease, which is characterized by a decline in the heart's ability to pump blood efficiently enough to meet the body's metabolic demands. Despite substantial advances in our understanding of the underlying pathophysiology and the therapeutic management of acute and chronic HF in recent years, the outlook of patients with these conditions remains poor. Not only is mortality and morbidity discouragingly high, but also the patients' quality of life remains impaired because of a substantial symptom burden. In the United States alone, HF is responsible for almost 1 million hospital admissions (more than for all forms of cancer combined) and >50,000 deaths each year, with estimated annual costs exceeding $20 billion. HF has an overall prevalence of 5 million and an incidence of more than 550,000. Despite improved patient information, beneficial changes in lifestyle and better treatment options, HF remains to be a major public health problem in industrialized nations and the leading cause of hospitalization in people older than 65 years. At a time when other cardiovascular diseases are on the decline, HF is rising and likely to escalate further over the coming decades due to an aging population and increased survival from the underlying causes such as coronary heart disease and hypertension.
BENEFITS
- Identification of BH4 supplementation as a means to improve diastolic function
- Shown to improve diastolic function in an animal model of diastolic dysfunction
- Could be administered as a dietary supplement
- BH4 already used in humans to treat PKU
IP STATUS:
US provisional patent application was filed on August 25, 2006 (60/840,368).
A US non-provisional application was filed August 27, 2007 (11/895,883).
FOR MORE INFORMATION CONTACT:
Saleem Sheredos
Program Manager
Technology Transfer Program
Veterans Affairs
Office of Research & Development (12TT)
5th Floor
103 South Gay Street
Baltimore, MD 21202
202-380-5080
Fax 410.962.2141
e-mail: saleem.sheredos@va.gov