It’s not unusual for scientists to focus their work in one direction, only to discover something unexpected. Researchers within the Darby Children’s Research Institute at the Medical University of South Carolina (MUSC) have discovered a gene mutation directly involved in the metabolism of the most common and perhaps most known medication used to treat ADHD, methylphenidate (MPH), or Ritalin®. This research is described in full detail in the June 2008 issue of the American Journal of Human Genetics.
“It was really serendipity to come across this individual with the gene mutations, as he was part of a normal volunteer study we were working on,” said John S. Markowitz, Pharm.D., associate professor in the South Carolina College of Pharmacy’s Department of Pharmaceutical & Biomedical Sciences, who along other members of the Laboratory of Drug Disposition and Pharmacogenetics and additional collaborators worked on the unfolding discovery. “When it became clear that this individual could not metabolize or deactivate the psychostimulant methylphenidate, we immediately began to wonder about his genetic makeup and discovered that this individual had two gene mutations that had not been previously reported.”
Normally, MPH is quickly deactivated after taking a pill several times a day or through the use of time-release formulations. The carboxylesterase-1 gene (CES1) encodes for the principal liver enzyme that governs the metabolism of MPH, widely considered the “gold standard” treatment for ADHD. The discovery that individuals with a mutation in the CES1 gene has, for the first time, provided clinicians a means to pre-test individuals prior to the usual trial-and-error method used when choosing an initial ADHD medication. Currently, predicting how an individual might respond to any ADHD medication isn’t generally possible.
Imagine the relief a patient or parent of a treated child might feel, having access to advance testing to be sure that they can adequately metabolize this medication and avoid adverse effects and potential toxicity. Furthermore, pre-testing cold avoid the unnecessary time and expense of a failed drug trial by allowing the treating clinician to screen for the mutation and initiate a different type of drug at the outset of treatment that uses a different enzymatic pathway if the mutation is present.
“This discovery has told us a lot more beyond the MPH pharmacotherapy, and has led us to focus more closely on the wider implications the mutation itself and the CES1 enzyme produced. Importantly, there are all kinds of other medications with representatives from almost every drug class referred to as pro-drugs, including common blood pressure medications, that require functional CES1 to metabolize those drugs into their active forms,” Markowitz said. “Without functional CES1 to activate the administered drug, there is a very real potential for individuals taking these pro-drugs to experience medication-related problems. For instance, if it seems that the dose is not having its intended effect, many clinicians would increase the dose a few times before changing medications and the inactive or less active parent drug administered may accumulate and run the risk of unanticipated toxicity for the patient.”About MUSC
Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
22.05.2018 | Life Sciences
22.05.2018 | Earth Sciences
22.05.2018 | Trade Fair News