In 1953, an American biochemist and a British physicist working together in Cambridge, England, identified the structure of DNA — the molecule of life — which passes genetic information from one generation to another. This discovery has unleashed an explosion of knowledge over the last half-century leading directly to the Human Genome Project and to the promise of personalized medicine.

According to the Personalized Medicine Coalition, people vary from one another in many ways — what they eat, the types and amount of stress they experience, their exposure to environmental factors — and their DNA. Many of these variations play a role in health and disease. Personalized medicine allows the use of new methods of molecular analysis to better manage a patient's disease or predisposition toward a disease.

It is already clear that personalized medicine promises three key benefits — better diagnosis and earlier interventions, more effective therapies, and more efficient drug development. For example, personalized medicine takes advantage of our growing knowledge of the genetic basis for varying individual responses to drugs. It explains why some individuals derive benefit, while others do not. It answers questions that arise when some individuals suffer side effects, while others do not.

“We now routinely incorporate these pharmacogenetics studies into our clinical evaluations of potential new medicines,” says neurologist Allen D. Roses, M.D., Senior Vice President, Pharmacogenetics, GlaxoSmithKline, one of the leading pioneers in this field.

“We can hope that over the next several years physicians will have more medicines available for prescription according to a patient's genetic makeup,” says Roses. “The whole idea is to get the right drug to the right patient.”

Roses, who spent 27 years at Duke University Medical Center — 20 of those years as Chief of the Division of Neurology — is one of the first clinical neurologists in the world to apply molecular genetic strategies to neurological diseases. Much of his focus has been directed toward cutting-edge research on Alzheimer's disease. One example of this effort is in the clinical evaluation of a drug for this illness.

According to Roses, the drug is an extended-release formulation of a product already marketed for type-2 diabetes called rosiglitazone. In a Phase II clinical trial, Roses and his colleagues did not see evidence of effectiveness when they considered the study population as a whole. When they looked at groups within that population who could be defined by their genetic makeups, however, they identified individuals who appeared to benefit from rosiglitazone.

In addition to his work in Alzheimer's disease, Roses and his colleagues are making progress in identifying the genetics that underlie susceptibility to side effects of certain drugs for AIDS and cancer. He is excited about the promise of personalized medicine, when even more developing drugs can be focused for safety and effectiveness.

“Perhaps if we viewed the health of our children and their children more realistically, the testing of medicines for prevention would become more fertile. Prevention takes years to measure clinically, and market protection for developing such drugs will need to be changed more positively.”

Elias Zerhouni, M.D. Director of the National Institutes of Health (NIH), says that the NIH is adopting a new approach to staying well by adopting a vision that emphasizes personalized precise medicine. To pursue this vision requires a major expansion of research, particularly in the area of genetics. To accelerate such discovery, the NIH has initiated support for genome-wide association studies.

“We can now clearly envision an era when the treatment paradigm of medicine will increasingly become more predictive, personalized, and preemptive,” he says. “We will strike disease before it strikes us with the hope of greatly reducing overall costs to society.”

Resources:

• The Mayo Clinic: Personalized medicine: Tailoring treatment to your genetic profile
• Environmental Health Perspectives Pharmacogenomics: The Promise of Personalized Medicine
• National Human Genome Research Institute Personalized Medicine: How the Human Genome Era Will Usher in a Health Care Revolution (Video and power point slides)