A Numbers Game
There are more than 7,000 rare diseases in the world. Most are genetic and affect only a small percentage of the global population.1 Neurofibromatosis (NF), Lou Gehrig's disease, and Tourette's syndrome are just a few of the better known of these “orphan diseases.” They are so named because they are often neglected by the medical community, which has little understanding and even less financial incentive to invest billions of dollars and years of research into developing targeted drugs for their treatment or possible cure. So they are largely abandoned.2
Taken together, however, these orphan diseases affect over 350 million people around the globe. If they all lived in the same country, they would constitute the world’s third largest population. Because most are unsupported and untreated, they also constitute the leading causes of infant death in the first year of life. Without the medicines needed to combat their illness, three out of 10 children with a rare disease will not live to see their fifth birthday.3
Looking For A Needle In A Haystack
Considering that orphan diseases receive little or no attention from the medical community, it seems fitting that drugs targeting those illnesses also carry the orphan name. Since only 1 in 5,000 drugs in preclinical testing actually make it to the marketplace, there are countless chemical compounds included in the ranks of potential orphan drugs. These are among the novemdecillion drug compounds (that is a 1 followed by 60 zeroes) that scientists at Duke and the University of Pittsburgh recently say exist.4
Such a rich field of scientific exploration has always engendered a fair amount of drug repositioning. Most of it has been by accident. Even Coca-Cola was originally intended as a substitute for morphine addiction. Considering that biopharmaceuticals spend an estimated $2.6 billion to develop a single prescription drug, there is a growing interest in drug repositioning among Big Pharma to save money, time, and possibly develop new drugs for other diseases that may have been previously bypassed as having no real return on investment. While that attitude is changing, such efforts continue to face a difficult challenge: how to best sort through the literal explosion of available data to identify the most promising candidate drugs.5
Building A Better Mouse Trap
That very challenge recently faced a team of scientists, biotechnologists, and computer analytics specialists determined to unravel the mysteries of neurofibromatosis, a rare and horrible genetic disease that affects 1 of every 3,000 newborns. Drawn from the National Center for Biotechnology-Superior Council for Scientific Research in Madrid, global life and environmental health leader PerkinElmer, and supported by the Children’s Tumor Foundation in New York, the team embarked on a quest to develop a free online database called NFFinder. Its initial objective was to locate potential drug treatments for NF, its namesake. It soon became clear that NFFinder holds the promise to revolutionize the treatment of rare diseases around the world.6
How It Works
NFFinder is a first free web-based bioinformatics research tool. It uses a huge database of genetic and microRNA information drawn from several sources to find possible relationships among diseases, drugs, observable traits (called phenotypes), and published experts in various fields of interest.
After researchers input their data, NFFinder returns experiments that have similar or opposite gene profiles along with a correlation score and a statistical significance valuation. Its dashboard also features a visual interface option based on TIBCO Spotfire® technology from PerkinElmer that its developers say presents data in a highly graphical environment that allows users “to explore, select, filter, and display result views centered in drugs, diseases, gene expression signatures, and expert authors.”7
But does it work? The NFFinder team leveraged the online tool to uncover antitumor drugs that could potentially kill the cell line responsible for NF. The search eventually focused on trichostatin A (TSA), an enzyme inhibitor and anticancer drug that stood out as a potentially effective treatment for NF.
Equally important, the research team found NFFinder to be a powerful new tool in suggesting specific therapeutics for NF and other rare diseases. While much more research is required, NFFinder is already proving that the search for new treatments for rare diseases is no longer a question of “if,” but of “when.”
See NFFinder in action for yourself.
Global Genes, Rare Diseases: Facts and Statistics
Rare diseases and orphan drugs, British Journal of Clinical Pharmacology, Volume 61, Issue 3, pages 243–245, March 2006.
A Library of Every Drug That Could Ever Exist, Popular Science, Posted April 24, 2013.
Drug repositioning: Re-investigating existing drugs for new therapeutic indications, Journal of Postgraduate Medicine, Volume 57, Issue 2, pages 153-160, April-June, 2011.
Nffinder: An Online Bioinformatics Tool for Searching Similar Transcriptomics Experiments in the Context of Drug Repositioning, Nucleic Acids Research, Oxford University Press, First published online: May 4, 2015.