One Size Does Not Fit All: The Case for Translational Medicine.

One Size Does Not Fit All: The Case for Translational Medicine.

Publication date: Mar 10, 2019

Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are integrated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunctional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.

Chowers, Y. One Size Does Not Fit All: The Case for Translational Medicine. 04200. 2019 Rambam Maimonides Med J.

Concepts Keywords
Autophagy Therapy
Biomarkers Sirolimus
Clinical Trials Autophagy
Differential MTOR inhibitors
Drug Therapy Inflammatory bowel disease
Genetic Loci Autoimmune diseases
Genetic Polymorphisms Signal transduction
High Throughput Screening Medical specialties
Homogeneous Medicine
Immunosuppression Branches of biology
Inflammatory Bowel Diseases Drug therapy
Maimonides Immunosuppression
Pathogenesis Continuum disorders
Rambam IBD
Rapamycin Autophagy alternative systems


Type Source Name
drug DRUGBANK Sirolimus
disease MESH multiple
drug DRUGBANK Spinosad
disease DOID IBD
disease MESH inflammatory bowel diseases

Original Article

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