Catapults, and the cannon that came after them, were major technical advances in their time. Targeting them to successfully defend against an enemy invasion, however, often depended as much on educated guesswork as it did on science and engineering.
Weapons that fight disease face similar challenges. State of the art treatments may work well in a mass population, but when aimed at helping one specific individual, it’s hard to predict which drug in what dosage will be on target.
That’s because patients are as different as their DNA. Their risks for diseases and side effects and their responses to intervention are influenced by a near infinite combination of genetic factors.
Now medicine is getting what could well be its own equivalent of a laser targeting system—genome-based personalized medicine.
“We’ll be using the tools of genomics to customize the risk assessment, diagnosis and management of both rare and common disorders to individuals to fit their unique needs and medical background,” Bruce Korf, MD, PHD said.
Chair of UAB’s Department of Genetics and new Personalized Medicine program, Korf is past president of the American College of Medical Genetics, was formerly Medical Director of Harvard-Partners Center for Genetics and Genomics, and is an internationally regarded authority in neurofibromatosis.
The program is now being configured, with the launch of two pilot programs planned in the first and second quarter of this year.
“Personalized medicine consists of two major components - genome sequencing and pharmacogenetics,” Korf said. “The cost of sequencing has come down so dramatically, it’s now possible to sequence a whole genome for a few thousand dollars, and the exome which encodes for protein, where most conditions that cause major medical problems seem to reside, for about $1,000. That cost should continue to drop rapidly.
“Many patients have conditions that we feel have a strong genetic basis that we haven’t been able to get to the bottom of after years of trying. Autism spectrum disorders and cognition and neuropsychiatric problems are examples.” Korf said. “With array comparative genomic hybridization, we have been able to improve our detection rate and increase the diagnoses we can make. We’re hoping that with exome sequencing, we’ll be able to push that rate significantly higher.
“We also want to help patients who have been on a diagnostic odyssey, going from doctor to doctor and taking test after test without getting an answer. We hope to shorten that search by identifying genes underlying the problem. Ultimately, it could help reduce cost by reducing the number of tests needed to diagnose the disorder.”
The second part of the program is pharmacogenetics, which is aimed at understanding how individual genetic factors and drugs interact.
“We’re working on developing tests to determine the right drug, in the right amount for the right person,” Korf said. “It’s also about matching the drug to the disease. For example, different tumors respond to different medications. Blood thinners are another good case in point. There is a narrow window that differs in individuals—too much and you can have a hemorrhage, too little and there can be lethal clots.
“Now, you have to make your best estimate and adjust up or down. But soon, when a patient comes into our emergency room, we’ll be able to check to see if we have his genome on file. If we do, our information system should be able to automatically suggest the most likely optimal dose.
“It’s also becoming practical to do near real-time testing for emergency situations within an hour or so. Our lab is installing equipment now to do that as part of a national trial.
“In many ways, what’s happening now in genetics and genome-based medicine reminds me of computer and mobile phone technology and how quickly the capabilities advanced as the costs went down,” Korf said. “The advances are coming much faster, though. If this were your smart phone, instead of replacing it every year, you’d be replacing it every month. “
Other genetic research at UAB is making significant progress toward new therapies for ovarian, cervical and breast cancer and other tumors, as well as sickle cell disease, and in understanding the genetic influences in Parkinson’s disease, obesity and diabetes.
Physician education will also be part of the personalized medicine program at UAB. “We want physicians to understand how genomics fits into their medical practice and how to work with information systems as a pathway to deliver point of care support,” Korf said. “Eventually, being able to rely on genetic information as a reference in making medical decisions is likely to become part of routine care.”
