6 minute read
Screening for clinical trial candidates
from i&E Bio Edition 2022
by Shannon Carr
SCREEN DREAM
OMRF develops patientscreening model for OA clinical trials
Osteoarthritis is among the world’s most diagnosed diseases, affecting an estimated 7% of the global population. The Centers for Disease Control and Prevention says roughly 32.5 million American adults live with the condition, making it the nation’s leading cause of disability.
Still, no medications exist to slow or stop OA. Currently available approved drugs treat only short-term symptoms of OA and don’t target the underlying causes or long-term progression of the disease. The Oklahoma Medical Research Foundation aims to change that.
Conducting effective clinical trials presents a major hurdle in the development of drugs to alter the underlying disease process. Such trials typically require thousands, or tens of thousands, of participants and take decades to complete, as the disease does not progress uniformly. This can render the assessment of investigational OA drugs extremely difficult – and expensive.
“The entire field of OA research has been trying to develop predictive models for that small percentage of patients whose disease will rapidly progress over a much shorter time – ideally two years – because those are the ones you need for clinical trials,” said OMRF physician-scientist Matlock Jeffries, M.D.
Dr. Jeffries has created such a screening process. His invention could be a game-changer for clinical trials by drastically reducing the time, the number of participants, and the cost of testing new OA drugs.
“My main goal is to empower pharmaceutical companies who are dissuaded from entering the OA market because of the total time currently needed for clinical trials,” he said.
Dr. Jeffries’ lab focuses on epigenetics, specifically, the methylation of DNA – a biological process by which methyl groups are added to the DNA molecule without changing its genetic sequence.
He based his model on DNA methylation data obtained from several hundred OA patients. Users can extrapolate the data for comparison against the blood samples of prospective clinical trial participants. The patented process predicts the future progression of pain and joint space narrowing.
“Our accuracy is in the 80% range, and the big advantage of our model is that it allows for a blood draw at a single point in time when all the patients look the same,” Dr. Jeffries said. “We can pull out which of those patients are going to show disease progression in the next two to three years, which is exactly what you want from a clinical trial perspective. I believe this model provides that level of certainty.”
He’s now working on a new test that would provide the same level of predictability at a reduced cost.
“And then after that, the next step is applying the same technique to a different OA subset,” Dr. Jeffries said. “This initial model is based on patients who were already experiencing pain and joint narrowing. So now the question is, can you take a person who currently has none of those symptoms and predict whether they will develop OA in the next couple of years.”
To learn more about licensing opportunities for this technology, contact Hemangi Shah, Ph.D., OMRF’s technology development specialist, at hemangi-shah@omrf.org.
OMRF physician-scientist Matlock Jeffries, M.D., uses a liquid nitrogen tank, which operates at the extremely cold temperatures needed for storage of human tissue and other samples.
SCIENTIFIC PROGRESS
The Latest OMRF News
LEADERSHIP ROLE IN PARTNERSHIP
The National Institutes of Health recently named OMRF to lead an international public-private partnership a imed at developing more effective treatments for autoimmune diseases. OMRF scientists Dr. Joel Guthridge (1) and Dr. Judith James (2) were awarded grants totaling more than $18.5 million to provide the leadership, expertise and infrastructure for the Accelerating Medicines Partnership in Autoimmune and Immune-Mediated Diseases. James will chair the $58.5 million program. Separately, OMRF’s Dr. Darise Farris (3) is a co-lead investigator of the team focusing on Sjögren’s disease.
HOPE FOR LUPUS PATIENTS
The New England Journal of Medicine published results of a clinical trial involving OMRF physician-scientist Joan Merrill (4). The study illustrated the incremental advances that Merrill said will be key to solving lupus, a perplexing autoimmune disease that affects an estimated 1.5 million Americans, primarily striking women and disproportionately affecting African Americans, American Indians and Latinos. OMRF served as a trial site in an earlier pilot study for the investigational drug. The Phase 2 trial involved 117 clinics on four continents. Merrill served as lead author for the resulting research paper. Sepsis, the leading cause of death from infection, kills about 270,000 people per year in the United States – more than lung cancer, breast cancer and drug overdoses combined. OMRF’s Dr. Florea Lupu (5) received a five-year, $3.1 million grant from the National Institute of Allergy and Infectious Diseases to pinpoint when a particular protein in the body’s complement system morphs from friend into foe during sepsis by killing healthy cells and causing inflammation. Lupu’s goal is to develop a drug that inhibits the protein’s activation before it turns traitor.
THE BODY’S NATURAL BAND-AID
While studying the role of a certain molecule in lymphatic vessels, which are crucial in fighting infection, OMRF’s Dr. Courtney Griffin (6) stumbled onto a greater grasp of the omentum, a huge mass of abdominal tissue whose healing properties are established but poorly understood among scientists and physicians. “The time it added to our research was well worth it because it resulted in a far better understanding of this fascinating tissue,” Griffin said.
FRUIT FLIES UNMASK DISEASE
OMRF’s Dr. Wan Hee Yoon (7) used fruit flies to uncover the shared genetic roots of seemingly unrelated neurological and developmental issues in nine pediatric patients. The study, conducted at 35 research centers on four continents, involved children who suffered from symptoms including epilepsy, gait problems, an underdeveloped brain, and hearing and sight loss. Researchers found that each patient had mutations in the same gene, and Yoon proved the mutations weren’t just a shared trait but the actual cause of their disease. For now, this condition is known only by reference to the gene in which the mutation is found, OGDH. In a study that appears to have human ramifications, Dr. Tim Griffin’s (8) lab examined how diet and exercise affect the knee joints of mice. The scientists zeroed in on synovial fluid, the liquid that cushions the ends of bones and reduces friction as joints move. The OMRF researchers found that synovial fluid from obese mice that exercised modestly resembled the fluid in lean mice, even though the obese rodents continued eating a high-fat diet and didn’t lose weight. “What that tells us is that losing weight isn’t a requirement for having beneficial changes in the joint,” Griffin says.
DOPAMINE STUDIES
Using separate grants from the National Institute on Aging and the U.S. Department of Veterans Affairs, Dr. Mike Beckstead (9) is investigating the role of dopamine in both Alzheimer’s disease and opioid addiction. Dopamine is a chemical in the brain responsible for voluntary movement and the perception of reward. With colleague Dr. Bill Freeman, Beckstead hopes to build a clearer picture of the brain’s response to opioids. “Dopamine tells your brain, ‘Whatever you just did, do it again,’” he said.
WINNING TEAM
OMRF’s Dr. Patrick Gaffney (10) teamed with Dr. Jason Buenrostro of Harvard University to secure a five-year, $4.1 million grant to investigate the role of genetics in the development of lupus. The pair will study how the DNA of people with lupus differs from those without the disease. Scientists have made significant progress in uncovering genetic changes that predispose certain people to lupus, Gaffney said. “Now we need to go further into the weeds to understand what these changes do to DNA’s function.”
