SAN ANTONIO, Texas – In response to the emerging breakthroughs in gene-targeted therapy that are beginning to be realized in the field of oncology, Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute with the National Institutes of Health, said there is a bright but challenging future ahead for all of medicine regarding genetic research, including rheumatology.
In delivering the opening lecture here at the annual meeting of the American College of Rheumatology, Dr. Collins urged investigators in rheumatology to recognize the importance of pharmacogenetics, to take advantage of innovations as high throughput technology, haplotype mapping, and small molecule research, and to use the research that has already been conducted and put into the public domain. "It'll get there, but we're not there yet," he said. "Push yourselves to take advantage of these tools. The ground under us is moving very quickly."
To further encourage the attendees here, Dr. Collins quoted the former hockey great Wayne Gretzky, who attributed his success to skating "where the puck is going to be." That anticipatory mentality will bring pharmacogenetics to rheumatology in a meaningful way, he said.
Dr. Collins focused his talk on the accomplishments of the Human Genome Project, which began in 1990, the Project's discoveries, and the applicability of those discoveries to clinical medicine. Faced with the mission of decoding human DNA by 2005, the Project completed that task in 2003. Now that the "instruction book" has been identified, the next step is to apply the findings of genomics to clinical practice and society as a whole, he said, adding that the Project is committed to making all future findings publicly available.
In order to have clinically relevant findings, investigators are committed to elucidating the genetic pathway in every common disease, Dr. Collins said, noting that every chronic disease that is known "has some genetic contribution." Therefore, identifying these genetic susceptibilities will lead to developing targeted diagnostics, therapeutics, and preventive measures, he said.
Several candidate genes have been implicated in systemic lupus erythematosus (SLE), he said, particularly on chromosomes 2 and 6, and one locus on chromosome 2q35-37, shows promise. Gene sequencing in the suspected chromosomes has identified an "a" allele of a single nucleotide polymorphism in the intron of the PDCD1 gene, which may interact with other genes to create a susceptibility to SLE. If investigators identify such a susceptibility, it will probably involve the interaction of several mutations rather than one, he said.
In order to sharpen the focus on candidate genes in SLE and other diseases, investigators are also using haplotype mapping, which identifies abnormal patterns. To further studies in this field, the International HapMap Project is planning to develop haplotype maps involving 80% to 90% of the genome, Dr. Collins said. This three-year project began in October 2002. "The goal is to identify genetic and environmental risk factors for all common diseases," he said.
The promise of identifying preventive strategies and drugs that target specific genes has been seen particularly in cancer research, Dr. Collins said. He cited colorectal cancer, in which at-risk individuals are screened earlier and more frequently, and have premalignant polyps removed. Other examples include the development of imatinib mesylate (Gleevec) for chronic myeloid leukemia and, more recently, gefinitib (Iressa), which causes a dramatic response in the minority of non-small cell lung cancer patients whose disease is sensitive to the drug.
By making use of the available technology and research that has already been conducted, rheumatology investigators can expect to see similar advances, he said.
FOR MORE INFORMATION:
www.hapmap.org
www.nihroadmap.nih.gov