Personalized Medicine

toddSpring 2013

Using Genetics to Guide Treatment

By Jon Parham

Peter Crooks, Ph.D., is working on drug development based on a patient’s genetic makeup.

Peter Crooks, Ph.D., is working
on drug development based on
a patient’s genetic makeup.

Using a patient’s genetic makeup to find the best medical treatment may still seem like science fiction, but UAMS is already practicing personalized medicine and making plans to increase its commitment.

In the UAMS Myeloma Institute for Research and Therapy, a series of genetic markers in multiple myeloma tumors form a sort of fingerprint for the disease, pointing clinicians toward a personalized treatment plan for each patient. While at the UAMS Psychiatric Research Institute, genetic information can indicate which anti-depression medication will work better with a particular patient.

What is being called the UAMS Center for Innovation in Precision Medicine is beginning to take shape to organize UAMS efforts toward personalized medicine. This confluence of science and medicine, alternately called genomic or precision medicine, has its roots in the growing understanding of how a person’s genetic code can influence disease and treatment response.

“Across UAMS, we have groups working to assemble pieces of a center — but we’re still trying to identify the resources we need,” said G. Richard Smith, M.D., director of the UAMS Psychiatric Research Institute. “We need to do it now. For our patients we need to do this so we can assure them of the most effective care.”

As the state’s only academic health sciences center — combining patient care, education and research — UAMS is the only place in the state positioned to build on the opportunities of personalized medicine, Smith said. And with a mission to engage in activities that improve health and health care in Arkansas, it’s an imperative.

New Tools, New Treatments

The UAMS Myeloma Institute has long been at the forefront of identifying the genetic fingerprint of multiple myeloma. It was the Myeloma Institute that first identified different sub-types of multiple myeloma, a cancer of the blood’s plasma, based on the genetic makeup of the cancer cells.

Analyzing the genetic markers in myeloma cells, patterns emerged indicating a “low-risk” version of the disease and one that was “high-risk,” proving resistant to standard treatments. In 2009, the institute began what was believed to be the first clinical trials that based a patient’s treatment plan on the genetic makeup of the cancer cells.

“We continue to be encouraged by the results we are seeing that indicate that customized treatment based on gene expression profiling leads to increased survival rates,” said Bart Barlogie, M.D., Ph.D., Myeloma Institute director.

Saad Usmani, M.D., director of developmental therapeutics in the Myeloma Institute, said now more than ever, myeloma clinical researchers understand the specific cellular pathways involved in development of the more potent type of multiple myeloma.

“We take the disease signature and find targets for drugs — blocking the cellular pathways that shut off the cancer’s growth and push it toward cell death,” he said.

Partly enabling the advances at the Myeloma Institute are new tools such as recently acquired gene sequencing equipment that allows researchers to better study the molecular basis of cancer development. The sequencer details the sequence of genes in samples of malignant plasma cells. The results are compared to what is known of the human genome to look for genetic clues about myeloma development.

“We’re in an exciting era, as there are about 30 new medications coming for treatment of myeloma that are based on tumor genetics and how each patient might respond differently to a specific treatment,” Usmani said.

Not even 20 years ago, the median survival rate for a multiple myeloma patient was less than two years. Today median survival is around 10 years — with some patients surviving 20-plus years since diagnosis. That success is in large part due to the power and increased understanding of genomic medicine, Barlogie said.

Absolutely. No Question.

Mood disorders initially seem to have the most applicability to genomic medicine in the mental health area, Smith said. Most anti-depressant medications are processed in the liver, but they are not processed the same by all patients.

For a year, Jeffrey Clothier, M.D., medical director of the Psychiatric Research Institute, has been using genetic testing to guide treatment for patients diagnosed with depression. Patients referred to his program have failed multiple treatments with different types of anti-depression medications.

Examining specific genes related to drug response can show which patients metabolize medications more quickly, which can impact dosing strategies. The genetic results also may point to patients more prone to side effects from certain medications.

“It’s another tool that tells us which medications might work better with a particular patient and which medications we need to avoid due to potential side effects,” he said. “I am absolutely encouraged by what we’ve been able to do.”

Why a Center?

Each of UAMS’ many centers and institutes bring together research, academic and patient care resources to focus on a certain cause. From cancer (the Winthrop P. Rockefeller Cancer Institute) to vision (the Jones Eye Institute) to geriatrics (the Reynolds Institute on Aging), each has been able to attract nationally known researchers and clinicians as well as grant funding that has led to scientific advances and new medical treatments.

“We know from experience UAMS can develop institutes or centers that can bring together expertise that can make a difference in our patients’ lives,” Smith said. “I know we can do the same thing in genomic medicine.”

Planning has started for the UAMS Center for Innovation in Precision Medicine. Architects will soon begin drawing up designs for a major renovation of the molecular pathology laboratory, which will house many of the diagnostic and analytical tools needed.

“The Department of Pathology will serve as a hub of the operation since testing and precision diagnostics drive the practice of personalized medicine,” said Jennifer Hunt, M.D., chair of the Department of Pathology in the UAMS College of Medicine. “Such a center will capitalize on our growing expertise to operate the equipment, interpret complex testing results and utilize results to treat patients.”

The lab would be a centralized campuswide resource for the genomic medicine initiative. Then each department, institute or program could recruit or assign faculty to the project based on their interests and need.

Genetic tests can already identify risk for various types of cancer. As understanding of the human genome increases, more advanced testing promises to find new targets for treatment or disease prevention.

Peter Crooks, Ph.D., chair of the Pharmaceutical Sciences Department in the UAMS College of Pharmacy, is one of those working to develop new pharmaceutical weapons for hitting those targets.

“In our drug discovery research, the more we study the cells from individual patients we look at, the more idea we can get as to whether a new drug will be effective in 80 percent or 20 percent of the overall patient population,” Crooks said. “Then we can focus on developing the drug candidates with the most potential to be therapeutically effective.”

A team approach to personalized medicine is critical, Crooks said. It’s not just the basic scientists analyzing the proteins and cells in the lab but also the clinicians who see patients and develop treatment plans.

It’s not just the bioinformatics experts using powerful computing technology to look for clues within the genetic code; it’s also the toxicologist to ensure a new medication doesn’t have unintended side effects.

Commercial applications may boost the science. The UAMS BioVentures biomedical business incubator has a track record of taking scientific advances from UAMS researchers to the global marketplace in a way that helps medicine and economic development in the state.

Several companies that began around drug discoveries are among the 50 startups aided by BioVentures since its inception. Crooks said having access to the business expertise and resources of BioVentures could be another positive for drug development in the area of personalized medicine.

“It’s good to have such a facility available for faculty members to help them decide when the time is right to think about commercializing a discovery,” he said.

Drug development is a long and expensive process, Crooks said. The promise of personalized medicine could help spur faster access to new discoveries, but it will likely require pharmaceutical companies finding a way to make precision medicine a profitable business when a new drug discovery only works in a subset of a patient population.

Academic medical centers could help spur a new paradigm in drug development, he said, where personalized medicine is a more promising venture for researchers, patients and pharmaceutical companies.

“We are poised and ready to take off,” Hunt said of UAMS plans for advancing genomic medicine in the state. “Establishing the center will give us a place where everybody will be working toward the same goal — using advanced technology and clinical expertise to give patients optimal care.”