As researchers continue to unlock the secrets of the human genome, more advanced medicines that target specific genes can be expected. But it could take years for these kinds of advances to translate into pharmaceutical products.
The cancer treatment imatinib(Drug information on imatinib) (Gleevec) was the first to emerge as a molecular designer drug. It selectively blocks cellular proliferation by inhibiting tyrosine kinase. Blocking the enzyme prevents the rapid growth of white blood cells that occurs in patients with chronic myeloid leukemia.
Similar successes are likely to be seen in treatments for Alzheimer's disease because the illness has a well-characterized neurobiology, Lieberman said.
It is hard to predict how long it will take for genetic breakthroughs to result in the development of successful therapeutic agents, he said. The gene for Huntington's disease, for example, was discovered in 1993 but has yet to result in a treatment.
The same holds true for disorders such as cystic fibrosis and Rett syndrome. While the genes behind these disorders have been discovered, effective treatments based on that genetic information have not.
The idea of applying genomics to identifying genes that can point to targets for drug development is a very powerful one, and ultimately will revolutionize the way that treatments are developed, Lieberman said. However, "it's not necessarily an easy process."
The pace of research is accelerating as different types of genetic-based technologies are developed.
Linkage and association studies, in which researchers painstakingly examine possible genetic origins for disorders within families or isolated populations, are giving way to powerful technologies such as gene multi-array chips, which can hold the code for thousands of genes. These microchips are hybridized with a patient's tissue--whether it's postmortem brain tissue, spinal fluid or blood--in order to examine gene expression and look for differences associated with a particular disorder.
Proteomics, another emerging technology, searches for gene products, usually proteins, in biologic fluids or specimens.
"These are powerful ways that can help to ultimately identify targets for drug development and ultimately may lead to individualization and selection of treatments for specific patients," Lieberman said.NIMH Research
Most research begins in government-funded studies; the findings of which become public domain.
In September, the National Institute of Mental Health announced a new program that would expand its in-house research into the genetics of schizophrenia. "For the first time, we have half a dozen vulnerability genes to explore," NIMH Director Thomas Insel, M.D., announced in a press release.
Multidisciplinary research teams will examine how these genes work at molecular, cellular and systems levels to determine the "risk architecture" of schizophrenia and to examine changes in the brain that alter thinking and emotions in ways that are associated with the disorder. The work will involve everything from cell-culture models to brain imaging.
"Genes don't directly encode for the hallucinations, delusions and blunted affect of schizophrenia," said Daniel Weinberger, M.D., chief of the NIMH Clinical Brain Disorders Branch (CBDB). "Rather, there is a very complicated path between a gene's influence on the regulation and function of a protein and such psychiatric phenomena."
The studies--which will examine two versions of the COMT gene, as well as GRM3, DISC1, dysbindin and neuregulin--will attempt to identify biological tests for the disorder and ways to switch genes "on" and "off" in order to develop prevention and treatment strategies. "Such findings emerging from the fast-track intramural effort will serve to stimulate spin-off studies by extramural, or grant-supported, researchers," Insel added.
One gene identified by CBDB that looks like a risk factor for schizophrenia is COMT. The enzyme produced by COMT is one that already has a drug that can act on it, Lieberman said. This points to justification for developing drugs that act as COMT inhibitors.
In July, NIMH announced funding for the Center for Collaborative Genetic Studies on Mental Disorders at Rutgers University. The university's previous research center, also funded by NIMH, established more than 17,000 cell lines from blood samples and distributed more than 25,000 DNA samples to more than 100 investigators worldwide.
The new center will continue that work by enhancing research collaborations and developing novel methods for data analysis that will help in the replication of genetic discoveries, according to Steven Moldin, Ph.D., NIMH project director for the Center. "The Center's activities are expected to greatly accelerate gene discovery in mental disorders such as autism, mood disorders and schizophrenia, and lead to the identification of novel targets for new therapies," Molding stated in a press release. "Ultimately, we expect these results to revolutionize the diagnosis, treatment and prevention of these disorders."