I’m interested in quick and low-cost ways to discover and develop drugs for treating ROW (rest-of-world) diseases. I have posted on the “open source” approach in which publicly-financed institutions pool resources (not likely effectively, see “Open Source Sesame,” 3/3/11), on virtual biotech companies that leverage low overhead costs (see “Backyard Biotech,” 7/7/11), and on my model for using university-sourced drug candidates, government resources for translational research, out-sourcing, and local manufacturing (see ”Drug Development on the Cheap,” 11/4/10). So a report on a recent start-up company out of Stanford University, NuMedii (NuMedii), got my attention. NuMedii uses “novel and proprietary integration and inference algorithms that incorporate multiple data resources to infer Signatures of Efficacy (SOE)™ as a molecular and probabilistic representation of drug efficacy” (NuMedii Technology). My translation: they match up gene expression patterns found for approved drugs with their “negative” profiles found in human cell lines which are models for human disease. If they find a drug that “reverses” the negative pattern for a particular disease, that drug will be a good candidate for development as a treatment for that diseases (a better explanation is in a GenomeWeb article). NuMedii recently published a pair of papers that indicate that two drugs, topiramate and cimetidine, could be re-purposed to treat inflammatory bowel disease and lung cancer, respectively (“indicate” since their data from animal models have limited predictive value) (Sirota et al. 2011 and Dudley et al. 2011).
Cool, but what may NuMedii’s approach mean for discovering drugs for the undrugged or poorly drugged diseases of the rest of the world like tuberculosis, human African trypanosomiasis, leishmanisais, and malaria? The re-purposing existing drugs for the neglected disease, as well as prospecting in big pharma company libraries of drug-like compounds, has been and is being tried by the donor-funded product development programs (e.g., TB Alliance’s moxifloxacin, TBA Pipeline). And Mike Polastri of Northeastern University has pioneered the approach of finding approved drugs that target human proteins with known analogous proteins in parasites with some success at least to the compound identification stage (Pollastri Lab). And BIOVentures for Global Health published a solid report that included noting which drug targets overlap between commercial diseases (those on insurance companies’ list of reimbursable diseases) and a few of the neglected diseases (BVGH Innovation Gap).
Being a blatant amateur in drug discovery (and genomics and chemistry), I guess that the NuMedii approach could work for neglected disease drug discovery if one assumes an analogy between the infectious organism causing the neglected disease and the aberrant cells targeted by the latest generation of cancer drugs. A good drug for both would be one that kills the targeted cells without effecting the host cells. So if one had gene expression profiles of the bad actors, e.g., the TB mycobacterium as it hides in its latent stage, and compared those to profiles from human cancer cell lines before and after drug treatment, one may find candidates. Perhaps someone is doing this? I noted that the TB Alliance has a database of profiles (TB Expression). For the relatively few non-infective diseases the plague ROW populations (sickle cell anemia comes to mind, see my post “A Really Neglected Disease,” 7/29/10), the NuMedii approach may also be applicable if the gene expression data is available or obtainable.
A bottom line to this meander: since computers are faster and cheaper than screening robots, drug discovery for neglected diseases could benefit from the NuMedii approach and, if the company founders (one of whom, Atul Butte, is a fellow MIT alum) are so inclined to give it a try, I’m willing to write a plan with a modest ROI for their investors to try to find funding (first stop the Gates, of course). As Rochelle Long, chief of pharmacological and physiological sciences at the National Institute of General Medical Sciences, a sponsor of the NuMedii studies, was quoted in the Wall Street Journal Online: drug repositioning is a fishing expedition, but “this is really educated fishing.” (WSJ article).