The National Institutes of Health is launching the first integrated, drug development pipeline to produce new treatments for rare and neglected diseases. The $24 million programme jumpstarts a trans-NIH initiative called the therapeutics for rare and neglected diseases programme or TRND.

The programme is unusual because TRND creates a drug development pipeline within the NIH and is specifically intended to stimulate research collaborations with academic scientists working on rare illnesses. The NIH Office of Rare Diseases Research (ORDR) will oversee the programme, and TRND's laboratory operations will be administered by the National Human Genome Research Institute (NHGRI), which also operates the NIH Chemical Genomics Center (NCGC), a principal collaborator in TRND. Other NIH components will also participate in the initiative.

A rare disease is one that affects fewer than 200,000 Americans. NIH estimates that, in total, more than 6,800 rare diseases afflict more than 25 million Americans. However, effective pharmacologic treatments exist for only about 200 of these illnesses. Many neglected diseases also lack treatments. Unlike rare diseases, however, neglected diseases may be quite common in some parts of the world, especially in developing countries where people cannot afford expensive treatments. Private companies seldom pursue new therapies for these types of illnesses because of high costs and failure rates and the low likelihood of recovering investments or making a profit.

"NIH is eager to begin the work to find solutions for millions of our fellow citizens faced with rare or neglected illnesses," said NIH acting director Raynard S Kington. "The federal government may be the only institution that can take the financial risks needed to jumpstart the development of treatments for these diseases, and NIH clearly has the scientific capability to do the work."

The drug development process is complicated and expensive. Studies suggest that it currently takes more than a dozen years and hundreds of millions of dollars to take a potential drug from discovery to the marketplace. And the failure rate is high.

"This initiative is really good news for patients with rare or neglected diseases," said ORDR director Stephen C Groft. "While Congress has previously taken important steps to help these patients, such as providing incentives for drug companies under the Orphan Drug Act, this is the first time NIH is providing support for specific, preclinical research and product development known to be major barriers preventing potential therapies from entering into clinical trials for rare or neglected disorders. While we do not underestimate the difficulty of developing treatments for people with these illnesses, this programme provides new hope to many people world-wide."

TRND will work closely with disease-specific experts on selected projects, leveraging both the in-house scientific capabilities needed to carry out much of the preclinical development work, and contracting out other parts, as scientific opportunities dictate. Its strategies will be similar to approaches taken by pharmaceutical and biotechnology companies, but TRND will be working on diseases mostly ignored by the private companies. Importantly, TRND will also devote some of its efforts to improving the drug development process itself, creating new approaches to make it faster and less expensive.

If a compound does survive this preclinical stage, TRND will work to find a company willing to test the therapy in patients. There are several stages to the clinical trials process that can take several years before the safety and efficacy of a new drug is determined. FDA will only approve a drug for general use after it passes these trials. The clinical trials process is also expensive, but the failure rate is lower at this stage.

"NIH traditionally invests in basic research, which has produced important discoveries across a wide range of illnesses," said NHGRI Acting director Alan E Guttmacher. "Biotechnology and pharmaceutical companies have enormous strength and experience in drug development, but to maximize return-on-investment work primarily on common illnesses. TRND will develop promising treatments for rare diseases to the point that they are sufficiently 'de-risked' for pharmaceutical companies, disease-oriented foundations, or others, to undertake the necessary clinical trials. NIH's goal is to get new medications to people currently without treatment, and thus without hope."

NIH already has many components of the drug development pipeline within its research programmes. TRND will begin its work in collaboration with the NIH Chemical Genomics Center (NCGC), a center initially developed as part of the NIH Roadmap for Medical Research. NCGC has developed a robotic, high-throughput screening system and a library of more than 350,000 compounds that it uses to make basic discoveries and probe cellular pathways. NCGC also has developed a team of researchers skilled in developing assays representing disease processes that can be tested in its screening system, and has extensive experience building collaborative projects with investigators from across the research community. Molecules with potential therapeutic properties that emerge from the NCGC screening process could be fed into the TRND drug development pipeline.

"With this new funding, TRND will develop teams of scientists who can do the hard work of optimizing chemicals that we or others discover that may treat rare diseases and turn them into actual drugs," said NCGC director Christopher P Austin, who is also the senior advisor for Translational Research to the NHGRI director. "This will still be hard work and it will take time and produce failures. Unlike traditional drug development, however, where only successes are published, we will publish our failures as well, so everyone in the drug development community can learn from them. That alone could be revolutionary."

If all the preclinical hurdles can be crossed, a possible treatment must still be tested in a series of clinical trials. TRND will seek to take advantage of several NIH resources that can help launch human studies, including the NIH Clinical Center, the NIH Rapid Access to Interventional Development (NIH-RAID), and the Clinical and Translational Science Awards (CTSA) programme.

The Office of the director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programmes and activities of all NIH components. The Office of the Director also includes programme offices which are responsible for stimulating specific areas of research throughout NIH.

The National Human Genome Research Institute is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases.