Reported on Nature.com is news that the big pharmaceutical company Novartis is closing its neuroscience facility in Basel, Switzerland where it is headquartered. It joins other pharmaceutical companies like GlaxoSmithKline and AstraZeneca, both based in the United Kingdom, and US-based companies Pfizer and Merck, as well as the French company Sanofi, who are abandoning traditional drug-discovery programs that pursue treatments for brain disorders.
Novartis differs from these others in that it plans to pursue studies of the genetics of psychiatric and cognitive disorders, with the hopes of finding new treatment strategies.
Developing drugs for brain disorders has proven to be an expensive and unsuccessful proposition. Because the market is flooded with cheap, generic antidepressants, antipsychotics and other drugs that act on known targets in the brain, mostly neurotransmitter receptors, companies have been forced to look for radically new drug targets but the search This has forced companies to look for very different drug targets, which is difficult because so little is known about the biology of the brain and its disorders.
“Standard approaches to developing drugs for mental health have not reaped significant benefit in the past two decades,” says Ken Kaitin, director of the Tufts Center for the Study of Drug Development in Boston, Massachusetts. “But it is a dilemma for the companies because there is a large and growing market for these products.” Mental disorders are the largest disease burden worldwide, and current treatments are not particularly successful with most patients.
According to Mark Fishman, president of research for Novartis’ main research arm, the Novartis Institutes of BioMedical Research (NIBR), NIBR will open a new research division to study the genetics of psychiatry and cognitive disorders at its site in Cambridge, Massachusetts, taking advantage of academic strength in the area, including the Broad Institute, run jointly by Harvard University and the Massachusetts Institute of Technology, which has both major DNA-sequencing capacity and is dedicated to psychiatric genetics. “Progress based on neurotransmitters has become small and incremental,” Fishman told Nature. “Genetic analysis will provide a real scientific opportunity in psychiatric and cognitive disorders, even if new drugs only arrive in the distant future.”
Genomic study has identified many different genetic variants that work together to increase a person’s susceptibility to disease. One particular defect known as copy number variation, in which large chunks of DNA are added or lost, may cause a significant increase in risk for psychiatric disease. Scientists hope that understanding the biological function of these risk genes may provide information on how to prevent or treat diseases.
Genetic biomarkers—particular DNA sequence or variation—that allow companies to identify individuals who are likely to respond to a particular drug, says Kaitin, are the new target. “It’s the basis of personalized medicine — health plans are more likely to pay for a new drug if they are convinced it will work for the person it is prescribed for.”
The genetic approach has delivered encouraging results for a five-year, ($27-million) public–private partnership called NEWMEDS, launched in 2009 by the European Commission to speed the development of treatments for schizophrenia and depression. NEWMEDS coordinator Tine Bryan Stensbøl, director of research at the Danish pharmaceutical company H. Lundbeck in Valby, says that scientists in the group have used genome findings gathered from the Icelandic population by the Reykjavik-based genetics company deCODE to identify a copy number variant that they think will be important in understanding the pathology of schizophrenia.
It is interesting to note that not all companies are switching over. Johnson & Johnson is one of the few major international firms sticking to its original agenda. Head of neuroscience Husseini Manji says, “things are cyclical — for those who stay the course, the breakthroughs will finally come”.