NIH Therapeutics for Rare and Neglected Diseases Program announces = next=20 round of drug development projects

Researchers will begin drug development projects for rare and = neglected=20 diseases that include potential treatments for a musculoskeletal = disorder, a=20 cognitive dysfunction disorder, a virus that affects the central nervous = system=20 of newborns, a parasitic worm infection, a form of muscular dystrophy = and a rare=20 lung disease. The six new projects are part of the National Institutes = of=20 Health=92s Therapeutics for Rare and Neglected Diseases (TRND) = program.

"These projects reinforce NIH's commitment to translational research = and the=20 need to accelerate potential new treatments that benefit patients with = rare and=20 neglected diseases," said NIH Director Francis S. Collins, M.D., Ph.D. = "It is=20 wonderful that TRND scientists and their collaborators can advance such=20 promising projects that may have otherwise remained stalled due to a = lack of=20 scientific or fiscal resources."

Congress created the TRND program to facilitate the development of = new drugs=20 for rare and neglected diseases. TRND bridges the wide gap in expertise = and=20 resources that often exists between basic research discoveries and the=20 development and testing of new drugs in human subjects. As it develops = new=20 treatments, TRND also conducts research aimed at improving the drug = development=20 process. In contrast to conventional drug development efforts, TRND will = publish=20 successes and failures so that the broader drug development community = can=20 benefit from the work done.

To develop new medicines, TRND establishes partnerships with = academic,=20 government, biopharmaceutical and patient advocacy groups. TRND and its=20 collaborators focus on the optimization and pre-clinical development of = new=20 drugs, as needed, advancing them from Food and Drug Administration (FDA) = investigational, new-drug approval to first, in-human clinical = trials.

Typically, the success rate for such projects is low, with 80 to 90 = percent=20 of projects failing in the pre-clinical phase and never making it to = clinical=20 trials. This stage of drug development is called the "Valley of Death." =

TRND began five pilot projects to establish the proof-of-principle = and=20 operating protocols for the program soon after it was established in = 2009. Those=20 projects include potential treatments for the neurodegenerative disease=20 Niemann-Pick type C, the neuromuscular disorder hereditary inclusion = body=20 myopathy, the blood disorder sickle cell disease, a rare blood cancer = known as=20 chronic lymphocytic leukemia, and the parasitic worm diseases = schistosomiasis=20 and hookworm. The chronic lymphocytic leukemia and the sickle cell = disease=20 projects have recently received investigational new drug approval from = the FDA=20 and are in clinical trials.

Earlier this year, TRND approved its first four drug development = projects=20 from its initial solicitation. They focus on potential new treatments = for=20 Duchenne muscular dystrophy, a degenerative muscle disorder; fragile X = syndrome,=20 the most common inherited form of cognitive and developmental = disabilities;=20 cryptococcal meningitis, an infectious fungal disease; and core binding = factor=20 leukemia, a rare blood and bone marrow cancer.

"TRND selects projects based on their potential to move forward into = human=20 trials and transform patient care in diseases for which there is little = or no=20 therapy," said Christopher P. Austin, M.D., scientific director of the = NIH=20 Center for Translational Therapeutics, which oversees TRND and is = administered=20 by the National Human Genome Research Institute (NHGRI). "While such = projects=20 are high-risk, the scientific opportunities and medical needs are = compelling.=20 After rigorous scientific review, the new projects were selected to = maximize the=20 chance of success and to teach us important generalizable lessons about = rare and=20 neglected disease drug development."

The latest TRND projects, approved by the advisory council of the = National=20 Institute of Neurological Disorders and Stroke (NINDS) on behalf of NIH, = and the=20 collaborating principal investigators are:

An inhibitor compound for treatment of fibrodysplasia = ossificans=20 progressiva.
Kenneth D. Bloch, M.D., William T. G. Morton = Professor=20 of Anesthesia
Harvard Medical School, Massachusetts General = Hospital,=20 Boston.

Fibrodysplasia ossificans progressiva is a rare inherited disorder = where=20 muscle and connective tissue such as tendons and ligaments are gradually = replaced by bone. The compound under development has shown efficacy in a = mouse=20 disease model.

Novel therapy for treatment of creatine transporter=20 deficiency.
Rick Hawkins, Chief Executive Officer
Lumos = Pharma,=20 Inc., Austin, Texas.

Creatine transporter deficiency occurs from a mutation in a creatine=20 transporter gene that prevents the transport of sufficient levels of = creatine to=20 the brain and results in cognitive function disorder. The lead compound = has been=20 evaluated in mice with creatine transporter deficiency and resulted in = improved=20 brain metabolism and cognitive function.

A compound for treatment of neonatal herpes simplex=20 virus.
David W. Kimberlin, M.D., Professor of Pediatrics =
The=20 University of Alabama at Birmingham.

Neonatal herpes simplex virus is an infection transmitted from mother = to=20 child during childbirth. In preliminary studies, the candidate compound = that=20 will be advanced by this group shows anti-herpetic activity and can = penetrate=20 the central nervous system. This compound has received longstanding = development=20 support by National Institute of Allergy and Infectious Diseases, = including=20 funding of the current clinical trial that will collaborate closely with = TRND.

Development of a deuterium-modified compound for treatment of = Schistosomiasis.
Julie F. Liu, Ph.D., Director, Research=20 Management
CoNCERT Pharmaceuticals Inc., Lexington, Mass.

Schistosomiasis is a neglected tropical disease caused by parasitic=20 Schistosoma worms that afflicts more than 200 million people worldwide. = The=20 disease can cause severe anemia, diarrhea, internal bleeding and/or = organ=20 damage. Neglected diseases are conditions that inflict severe health = burdens on=20 the world's poorest people. This project aims to produce compounds that = retain=20 the positive anti-parasitic effects of the current treatment, = praziquantel,=20 which stuns and kills the worms while enabling lower and less frequent = doses=20 with potential for improved tolerability. This may allow broader access = of a=20 therapeutic to affected patients.

A drug candidate for treatment of Duchenne muscular = dystrophy.=20
Peter Sazani, Ph.D., Executive Director of Preclinical = Development=20
AVI BioPharma, Bothell, Wash.

Duchenne muscular dystrophy is an inherited, rapidly progressive form = of=20 muscular dystrophy affecting approximately 1 in 3,500 male births = worldwide.=20 This collaboration aims to develop a compound that would treat a = sub-group of=20 patients with a specific mutation responsible for Duchenne muscular = dystrophy.=20 The team will also investigate the general utility of this innovative = treatment=20 platform technology.

A pharmacological therapy for treatment of autoimmune = pulmonary=20 alveolar proteinosis.
Bruce C. Trapnell, M.D., Francis R. = Luther=20 Professor of Medicine and Pediatrics
Cincinnati Children=92s = Hospital Medical=20 Center-Research Foundation, Cincinnati, Ohio.

Pulmonary alveolar proteinosis is a rare lung disease characterized = by the=20 build-up of a grainy material in the air sacs of the lungs that causes = breathing=20 difficulties and can result in respiratory failure in rare cases. The = protein=20 therapeutic that is the subject of this collaboration will be developed = as an=20 inhaled therapy.

TRND has established data-driven milestones for each project to track = progress and allow projects which do not achieve milestones in the = established=20 timeframe to be terminated, thus allowing other promising candidates to = enter=20 the program. A project would be terminated, for example, if the new = treatment=20 fails to show effectiveness in animal models, demonstrates toxicity in=20 preclinical testing, or is found not to have the needed bioavailability, = the=20 amount of drug absorbed by the body.

"The goal of TRND is to work closely with project partners to achieve = scientific milestones that we hope will produce badly needed treatments = for=20 underserved patient populations." said NHGRI's John McKew Ph.D., chief = of NCTT's=20 Therapeutic Development Branch and director of TRND.

Under TRND's collaborative operational model, project partners do not = receive=20 grants. Instead, the partners form joint project teams with TRND and = receive=20 in-kind support from TRND drug development scientists, laboratory and = contract=20 resources.

The potential treatments are developed and modified as needed to take = them=20 through the many steps of the preclinical development process. For = projects=20 which fail to progress beyond a milestone and are terminated, efforts = will be=20 made to understand the reasons for failure, to improve our understanding = of the=20 drug development process and thus improve its efficiency. TRND projects = are=20 taken only to the point in development at which they can attract outside = funding; beyond this point the partner takes the project through the = remainder=20 of clinical development and regulatory approval process.

TRND projects are applied for via a solicitation process. The next=20 solicitation will open in the spring of 2012. Updated information about=20 solicitations and project information is available at http://nctt.nih.gov/TRND.

The National Human Genome Research Institute is part of the National=20 Institutes of Health. For more about NHGRI, visit http://www.genome.gov/.

About the National Institutes of Health (NIH): NIH, = the=20 nation's medical research agency, includes 27 Institutes and Centers and = is a=20 component of the U.S. Department of Health and Human Services. NIH is = the=20 primary federal agency conducting and supporting basic, clinical, and=20 translational medical research, and is investigating the causes, = treatments, and=20 cures for both common and rare diseases. For more information about NIH = and its=20 programs, visit http://www.nih.gov/.

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