Improving MS drug safety with genetics

In a new blog post, Kaarina Kowalec describes the field of pharmacogenomics and its impact on the search for safer, more effective treatments for multiple sclerosis.

Kaarina Kowalec is a PhD candidate in the UBC Pharmacoepidemiology in Multiple Sclerosis Research Group (led by MSFHR Scholar Dr. Helen Tremlett) and the Pharmaceutical Outcomes and Pollicy Innovations research unit (led by Dr. Bruce Carleton). In this blog post, she describes the field of pharmacogenomics and its impact on the search for safer, more effective treatments for multiple sclerosis.

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Interferon-β is the most widely used treatment for multiple sclerosis (MS) worldwide. However, its use is also associated with a variety of adverse drug reactions, including liver toxicity.

Adverse drug reactions are a major issue in modern medicine and are ranked as the fifth leading cause of death and cause of more than two million severe reactions annually in the United States. [1]

Drug-induced liver toxicity is the most common reason for acute liver failure in the United States. Liver toxicity has been associated with the use of interferon-β in MS treatment. Although some risk factors for liver toxicity are known, [2-3] it remains impossible to fully prevent this reaction. The identification of additional factors associated with this drug reaction would be highly valuable in the MS clinic.

To do this, we can study a patient’s inherited genetic material, DNA.

DNA and the genes encoded in DNA remain stable throughout a person’s lifetime and may provide an unprecedented means of predicting serious drug reactions. These genetic differences can alter the metabolism of a drug in the body. This area of science is called “pharmacogenomics”, as it studies an individual patient’s response to drugs – whether to identify the risk of experiencing a serious drug reaction or to predict who will benefit from the drug.

For example, there are several drugs on the market today that can cause fatal adverse drug reactions (e.g., abacavir for HIV therapy), but patients are now tested before the drug is administered to ensure the patient does not have genetic susceptibility to the adverse reaction.

Similar findings have been identified in drugs for cancer [4] and cardiovascular disorders, with genetic information now included on the labels of more than 70 drugs. [5] Testing for these genetic markers is becoming more widely available as more cost-effective and rapid tests are developed.

To date, pharmacogenomic studies of MS have only focused on drug effectiveness. This has created a gap in preventing serious adverse drug reactions, as well as opportunities to make treatment for people with MS more personalized and maximize drug safety.

Our research aims to unravel the complexities of adverse drug reactions in people with MS, starting with liver toxicity from interferon-β. In collaboration with the Canadian Pharmacogenomics Network for Drug Safety, we have successfully recruited patients from across Canada, the United States, and abroad and hope to have preliminary results by next year.


References

  1. Lazarou, J., Pomeranz, B.H. & Corey, P.N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 79, 1200-1205 (1998).
  2. Tremlett, H.L., Yoshida, E.M. & Oger, J. Liver injury associated with the beta-interferons for MS: a comparison between the three products. Neurology 62, 628-631 (2004).
  3. Chan, S., Kingwell, E., Oger, J., Yoshida, E. & Tremlett, H. High-dose frequency beta-interferons increase the risk of liver test abnormalities in multiple sclerosis: a longitudinal study. Mult Scler 17, 361-367 (2011).
  4. Ross, C.J., et al. Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy. Nat Genet 41, 1345-1349 (2009).
  5. Food and Drug Administration (FDA). Pharmacogenomic Biomarkers in Drug Labels. Available at: www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm0833... (2013).

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