Precision Medicine: Making Warfarin Safer

Blood sample for PT INR test, diagnosis for coagulation disease

Caption: Finding the right dose of the drug warfarin can be tricky, even with this standard test to measure how fast a person’s blood clots.
Credit: Thinkstock/jarun011

Every year, thousands of older Americans require emergency treatment to stop bleeding caused by taking warfarin, a frequently prescribed blood-thinning pill. My own mother received this drug in her later years, and her doctors encountered significant challenges getting the dose right. The problem is too much warfarin causes potentially serious bleeding, while too little leaves those who need the drug vulnerable to developing life-threatening clots in their legs or heart. The difference between too little and too much is distressingly small. But what if before writing a prescription, doctors could test for known genetic markers to help them gauge the amount of warfarin that a person should take?

Such tests have been available to doctors and patients for a few years, but they have not been widely used. The recent results of a national clinical trial offer some of the most convincing evidence that it’s time for that to change. In this study of 1,650 older adults undergoing elective hip or knee surgery, patients whose genetic makeup was used to help determine their dose of warfarin were less likely to suffer adverse events, including major bleeding. This trial marks an encouraging success story for the emerging field of pharmacogenomics, the study of how the variations in our genes affect our responses to medicines.

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Sickle Cell Disease: Gene-Editing Tools Point to Possible Ultimate Cure

Sickled red blood cell

Caption: An electron micrograph showing two red blood cells deformed by crystalline hemoglobin into different “sickle” shapes characteristic of people with sickle cell disease.
Credit: Frans Kuypers: RBClab.com, UCSF Benioff Children’s Hospital Oakland

Scientists first described the sickle-shaped red blood cells that give sickle cell disease its name more than a century ago. By the 1950s, the precise molecular and genetic underpinnings of this painful and debilitating condition had become clear, making sickle cell the first “molecular disease” ever characterized. The cause is a single letter “typo” in the gene encoding oxygen-carrying hemoglobin. Red blood cells containing the defective hemoglobin become stiff, deformed, and prone to clumping. Individuals carrying one copy of the sickle mutation have sickle trait, and are generally fine. Those with two copies have sickle cell disease and face major medical challenges. Yet, despite all this progress in scientific understanding, nearly 70 years later, we still have no safe and reliable means for a cure.

Recent advances in CRISPR/Cas9 gene-editing tools, which the blog has highlighted in the past, have renewed hope that it might be possible to cure sickle cell disease by correcting DNA typos in just the right set of cells. Now, in a study published in Science Translational Medicine, an NIH-funded research team has taken an encouraging step toward this goal [1]. For the first time, the scientists showed that it’s possible to correct the hemoglobin mutation in blood-forming human stem cells, taken directly from donors, at a frequency that might be sufficient to help patients. In addition, their gene-edited human stem cells persisted for 16 weeks when transplanted into mice, suggesting that the treatment might also be long lasting or possibly even curative.

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