Steinburger- Recent scientific advances coupled with development of new research tools has resulted in rapid growth in interest in pharmacogenetics (PGx). As many commentators have noted, the technology replaces the ‘one size fits all’ approach characteristic of current therapy with one that seeks to deliver ‘the right drug at the right dose to the right person’.
The possible uses of PGx may be summarised as follows:
*reducing drug attrition by identifying metabolic pathways likely to give rise to adverse drug reactions (ADRs) early in clinical studies – the most common use for PGx by pharmaceutical companies in drug development;
*new drug development for “niche” markets based on genotype or gene expression, such as targeted cancer drugs (which may be ‘blockbusters’ in terms of sales);
*development of previously withdrawn products or ‘failed’ drug candidates for targeted groups (‘drug rescue’);
*reducing ADRs of licensed drugs by targeting patients according to genotype;
*improving efficacy of licensed drugs by targeting patients according to genotype.
Of these five possibilities, the drug industry is concentrating on the first two, with smaller genomics companies focusing on the third option, either independently or in collaboration with pharmaceutical companies. The last two options offer the opportunity to apply PGx to the potentially important area of already licensed drugs…
DNAPrint applies novel technologies for stratifying patient populations, using structured-association pharmacogenomics methods with proprietary marker panels and innovative computational modeling.
DNAPrint’s pharmacogenomics method is based on our understanding of how the genome is not only a blueprint of individuality, but also a record of our ancestral heritage. Drug metabolism and therapeutic effects are fundamental, adaptive functions developed in response to dietary and environmental xenobiotics, which are appreciably different between regions of the world, with different climates, fauna and flora. Human populations arising in such distinct habitats have developed variant systems for coping with them, for example, the highly polymorphic drug-metabolizing enzymes (e.g., CYP family of proteins). These types of adaptations remain embedded in our genomes over generations and are shared within populations as they expand and persist. Thus, determination of genetic ancestry admixture in patient populations, at the level of the individual patient, is an important parameter for better resolution of subpopulations according to proclivity for beneficial and/or adverse drug responses.
- The concept of tailoring drug discovery and development, even drug programmes, according to ethnic make-up is seen as the next step in producing the next generation of increasingly effective drugs. Until the specific response pathway for each drug becomes possible and economically viable, biogeographical ancestry admixture will be used as a surrogate for predicting response.
"One could conceivably use our AIM technology during Phase I and II to plan Phase III, but also develop a specific (gene variant based, not AIM based) pharmacogenomics test to accompany the drug during Phase III or later," Tony Frudakis
Application of these technologies is expected to enable the company to develop more efficient medicines for segmented markets.
Some recommended reading :
Docket Management Docket: 02D-0018 - Collection of Race and Ethnicity Data in Clinical Trials for FDA Regulated Prodcuts; Draft Guid
Comment Number: EC -2
Commentor Dr. Tony Frudakis
US FDA: Guidelines for Pharmacogenomic Data Submission. (2005).
US FDA: Concept Paper: Drug–Diagnostic Co-Development (Theranostics). (2005).
Frudakis T: Molecular Photofitting: Predicting Ancestry and Phenotype Using DNA. Elsiever Academic Press, MA, USA (2007).
Halder I, Shriver M, Thomas M, Fernandez J, Frudakis T: A panel of ancestry informative markers for estimating individual biogeographical ancestry and admixture from four continents: utility and applications. Hum. Mut. (2007) (In Press).
Bauchet M, McEvoy B, Pearson LN et al.: Measuring European population stratification with microarray genotype data. Am. J. Hum. Genet. 80(5), 948–956 (2007). [CrossRef] [Medline]
Frudakis T, Thomas M, Ginjupalli S, Handelin B, Gabriel R, Gomez H: CYP2D6*4 polymorphism is associated with statin-induced muscle effects. Pharmacogenet. Genom. 17(9), 695–707 (2007).
Frudakis T, Terravainen T, Thomas M: Multilocus OCA2 genotypes specify human iris colors. Hum. Genet. 122, 311–326 (2007). [CrossRef] [Medline]
DNAPrint Genomics, Inc.: better drugs for segmented markets
Tony Frudakis. Pharmacogenomics February 2008, Vol. 9, No. 2, Pages 247-251
Race and ancestry in biomedical research: exploring the challenges
Timothy Caulfield1, Stephanie M Fullerton2, Sarah E Ali-Khan3,
Laura Arbour 4, Esteban G Burchard5, Richard S Cooper6, Billie-Jo Hardy3,
Simrat Harry1, Robyn Hyde-Lay7, Jonathan Kahn8, Rick Kittles9,
Barbara A Koenig10, Sandra S-J Lee11, Michael Malinowski12,
Vardit Ravitsky13, Pamela Sankar13, Stephen W Scherer14, Béatrice Séguin3,15,
Darren Shickle16, Guilherme Suarez-Kurtz17 and Abdallah S Daar Published: 21 January 2009
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