Disease Diagnosis and Therapy Customized to Each Person’s Genetic Make-up

UBC Reports | Vol. 53 | No. 1 | Jan. 4, 2007

By Prof. Ronald Reid
Chair, Division of Biomolecular and Pharmaceutical Chemistry Faculty of Pharmaceutical Sciences

Personalized medicine based on the individuality of the human genome will allow physicians and pharmacists to accurately characterize disease and identify not only the best drug to be administered to a particular patient for a specific disease, but also the correct, safe, and effective drug dose the first time.

Pharmacogenomics uses information from the human genome to diagnose disease and predict the efficacy and toxicity of drug therapy, a concept that has come to be known as “personalized medicine.” The technology involved is complex, requiring large-scale experimental approaches combined with equally complex statistical and computational analyses. The fundamental strategy in a pharmacogenomics approach is to expand the scope from examining variations in single genes, proteins, and metabolites to studying the interaction of all genes, proteins, and metabolites that are relevant to disease diagnosis and a successful therapeutic outcome.

The application of pharmacogenomics to health care emphasizes that the present paradigm of “evidence-based medicine,” the techniques of which are derived from randomized and double blind clinical trials, is inconsistent with “personalized medicine.”

The application of statistical information derived from clinical drug trials on large populations results in a standard dose range for the population, which both overdoses and underdoses a small but significant portion of that population. The failure to recognize patients as individuals is likely a factor in adverse drug and toxic drug-drug interactions that account for 100,000 patient deaths, two million hospitalizations, and $100 billion in health care costs in the United States yearly.

Over the next 20 years, in an effort to effectively address the problems of adverse drug and toxic drug-drug interactions, pharmacogenomics research will further refine the paradigm of “personalized medicine” through the development of technologies to determine the precise biochemical changes, referred to as a metabolic phenotype, underlying a disease pathology and therapy and the elucidation of environmental factors (e.g., diet, lifestyle, culture, exposure to other chemicals, etc.) contributing to the many components of the metabolic phenotype.  By comparing the metabolic phenotypes of normal and disease states, nucleic acid, protein, and small molecule biomarkers descriptive of a disease phenotype can be identified.

Similar studies on the biochemical changes involved in drug therapy will provide biomarkers characteristic of drug metabolism, distribution, and drug action descriptive of successful therapeutic outcomes (therapeutic phenotype).  This will permit a better understanding of disease pathology, provide new drug targets for disease therapy, identify biomarkers characteristic of disease potential and development as well as biomarkers descriptive of drug efficacy and toxicity. 

For example, in the future, physicians will send off a patient’s urine sample for analysis of several hundred molecules (biomarkers) arising from the patient’s metabolism.  The pattern of concentration of these molecules in the disease state, compared to the pattern in a healthy individual, will enable individualized diagnosis and therapy, even in complex diseases such as schizophrenia. The analysis and results will be available to the physician within hours.

The development of the information technology (Health Informatics) necessary to make sense of this complex area is in the early stages of development.  As knowledge and technology progress, genomic information will come well within the realm of routine use.  Over the coming years, standard blood and urine tests augmented by new sources of medical data will yield a plethora of new information about a patient’s current and future health and provide new directions for individualized disease prevention and therapy.

These advances in biomedical knowledge and information systems will result in novel approaches to genetic counseling, patient education, risk assessment, medical decision making, monitoring treatment, privacy and regulatory issues, and patient empowerment, which will shift the emphasis of health care from the reactive response to illness to the proactive minimization of unnecessary morbidity over an individual’s lifetime.

Finally, the realignment of the medical paradigm from “evidence-based” to “personalized” via the application of pharmacogenomics should provide a viable solution to optimize disease diagnosis and patient therapy and significantly reduce costs to the health care system.