When Matthew Might's son was diagnosed in 2012 with the first case of NGLY1 deficiency -- an ultra-rare genetic disorder -- the computer scientist altered his career focus into genetics and drug development. He then pioneered the use of social media and search engine optimization to find other patients with the condition, which successfully bolstered the scientific research for the disease. As a result, two drugs were discovered as treatments for the disease.
That approach will now become part of the UAB Hugh Kaul Personalized Medicine Institute. "We're going to have a fairly unique focus on rare diseases," says Matthew Might, PhD, who has been named the inaugural director. Might joins UAB from the University of Utah, where he was a Presidential Scholar and an associate professor in both computer science and pharmaceutical chemistry, and from Harvard Medical School, where he is a visiting professor of biomedical informatics. "We'll be the only center that will be able to develop a drug for you from scratch."
Personalized medicine tends to be misunderstood, says Might, who was appointed as strategic leader to the White House Precision Medicine Initiative by former President Obama. "Personalized medicine isn't a discipline, but a way of doing medicine," he says. "It adapts to any medical discipline."
This has led to a new goal for the Institute of defining what personalized -- or precision --medicine means for every discipline. "What distinguishes precision medicine is the use of data," Might says.
Personalized medicine builds treatments based on data about the individual, not just the disease, including the patient's family history, lifestyle, environment and genetic profile. "The excitement right now is around the genome," Might says. "And there's due cause for that excitement in some areas. One of those is rare diseases and cancer."
The individualized approach is transforming cancer treatment. "We're switching from traditional oncology to precision oncology through sequencing individual tumors and using that in the selection of medicines," Might says.
Whereas treatment with chemo drugs often boils down to an effort to kill the cancer faster than the patient, precision medicine identifies the mutation causing the tumor and finds the therapy that targets that mutation. "This is a tremendous difference because we're hitting the root cause instead of broadly treating it with the blunt instrument of chemo," Might says. "We have to stop thinking of cancer as organ by organ and start thinking of it as gene by gene."
Characterizing and identifying the DNA or RNA sequences of cancer cells in a tumor has only been possible in the last few years. "A lot of physicians are hesitant about genomic sequencing because they don't understand what comes back -- the list of mutations that we think cause the genetic disease," Might says, adding that the UAB Personalized Medicine Institute can be helpful in translating those results.
The other concern with precision medicine stems from the price. Sequencing can run $1,000 to $8,000. But for some diseases, that cost can lead to a treatment that prevents far pricier outcomes. "For instance, some epilepsy is not well controlled, so you end up in the ER a lot," Might says. But if personalized medicine identifies the root cause and finds the therapy that stops the seizures, then ER costs vanish.
"Sequencing every disease is not cost effective yet, but we're trying to bring down the cost of individual screening," Might says. The UAB Personalized Medicine Institute plans to first target broad classes of genes which create a clear disease signature in the cell, like some epilepsies and even some forms of autism.
Because of the clear signature, a computer can test endless drugs on the mutated cell and easily spot improvements. "Just looking at the shape of the cell or its electrophysiology serves as a proxy for effectiveness of the medication for some diseases," Might says.
Though UAB will be devising new drugs for treatments, the emphasis for Might is utilizing existing drugs. "We're finding new uses for drugs not even thought of before," he says. "For example, you can treat some epilepsies with anti-parasitics or antidepressants because they happen to hit the right molecular target."
Finding effective therapies outside their traditional function has become almost the norm in precision medicine. "It happens basically every time," Might says. "The best drug would never have been picked by a human or an expert."
Unfortunately, the cost to screen for all approved drugs from around the world currently runs over $50,000 for some conditions. But Might believes the cost for some diseases will drop to under $20,000 within a few years as new screening models are developed, such as utilizing yeast for the models and compiling libraries of models to avoid repetition.
He also believes that because the science behind personalized medication can significantly raise the guarantee of the effectiveness of the therapy for that individual, then its cost-saving over the long haul of a disease can be proven. "We still have to convince payers of that," he says. "That's a discussion we're going to have with them."
Since precision medicine is relatively new, the scientific foundation for it is still being laid. "We don't fully understand the genome yet, so if you have a mutation and we have never studied that gene before, it's difficult to tell you what to do," Might says.
But that is when data-mining meets medicine. "Precision medicine combines the computation approach with the biological approach," Might says. "That's a favorite area of mine. Then you get a very tailored treatment for that patient."