Four new preclinical drug development projects at the NIH will target a form of blindness and diseases characterized by cardiac problems. The projects were selected for their potential to treat specific rare diseases and to help scientists uncover new information that can be shared with other researchers.

The studies will be funded through the Therapeutics for Rare and Neglected Diseases (TRND) program at the NIH's National Center for Advancing Translational Sciences (NCATS). This group of projects also marks the TRND program's first use of stem cells as well as its first collaboration with Eli Lilly to co-develop a treatment for a rare disease.

"TRND is grounded in partnerships with academic, government, pharmaceutical and patient advocacy groups. Working in collaboration, scientists conduct preclinical development of new drugs and then advance them to first-in-human clinical trials," said Christopher P. Austin, M.D., NCATS director. "Like all NCATS programs, TRND seeks to develop new technologies and more efficient paradigms for translation, in the context of important unmet medical needs."

Two projects employ therapeutic approaches to developing a treatment for retinitis pigmentosa, a severe form of hereditary blindness. A third project focuses on a potential treatment for hypoparathyroidism, a hormone-deficiency syndrome that can lead to cardiac problems and convulsions.

The remaining project aims to develop a possible therapeutic that targets a cardiac disorder associated with LEOPARD syndrome, an extremely rare genetic disease that affects many areas of the body. About 80% of patients with LEOPARD syndrome have a cardiac disorder called hypertrophic cardiomyopathy,  a thickening of the heart muscle that forces the heart to work harder to pump blood that can lead to early death.

A rare disease is one that affects fewer than 200,000 Americans. NIH estimates that, in total, there are more than 6,000 rare diseases. However, effective pharmacologic treatments exist for only about 200 of these illnesses.

Private companies often do not pursue new therapies for rare diseases due to the low anticipated return on investment. Through TRND, NCATS advances potential treatments for rare and neglected tropical diseases to first-in-human trials, an approach known as "de-risking." This strategy can make possible new drugs more commercially viable and attractive to outside partners, who can invest in their further development and additional clinical trials.

TRND partners do not receive grants. The collaborative project teams receive in-kind support and gain access to TRND researchers with rare disease drug development capabilities, experience and clinical and regulatory resources. Each project has established data-driven milestones to track progress. TRND staff may choose to discontinue projects that do not achieve milestones in the established timeframe. This allows other more promising candidates to enter the program.

A number of early projects fostered by TRND have reached the stage at which partners, such as pharmaceutical, biotechnology or disease groups, are being sought to move the treatments out of TRND and in the next phases of clinical development. Through the program in the last two years, TRND researchers and collaborators have advanced four projects to human clinical trials, evaluating treatments for sickle cell disease, chronic lymphocytic leukemia, hereditary inclusion body myopathy and Niemann-Pick Type C.