During a Scientific Sessions symposium jointly sponsored by the ADA and the American Society of Nephrology, four experts examined the role precision medicine trials might play in diabetic kidney disease research.
The virtual presentation, Targeting Diabetic Kidney Disease (DKD)—Are We Ready for Precision Medicine Trials? can be viewed by registered meeting attendees at ADA2020.org through early September.
“DKD is more than just one disease, therefore treatment must be based on the molecular mechanisms underlying the disease pathology,” said Wenjun Ju, PhD, Associate Research Scientist of Internal Medicine/Nephrology in the Department of Computational Medicine and Bioinformatics, Michigan Diabetes Research and Training Center, University of Michigan. “The challenge is how to distinguish patients based on their molecular mechanisms.”
Tobias B. Huber, MD, Professor and Chairman of the Department of Medicine at the University Medical Center Hamburg-Eppendorf, Germany, said mitochondria is an interesting therapeutic target. He outlined a new podocyte metabolism paradigm and presented research showing podocyte energy supply is mainly provided independent of mitochondria, with anaerobic glycolysis representing the main energy source.
“Mitochondria certainly play an important role, because this has been proved by human genetic diseases, potentially as a signaling center of podocytes in health and as ROS (reactive oxygen species) producers in disease,” Dr. Huber said.
Another challenge is identifying noninvasive treatment response biomarkers for patient stratification, said Dr. Ju, who cited work being done by the Nephrotic Syndrome Study Network (NEPTUNE) Match, led by Matthias Kretzler, MD, at the University of Michigan. NEPTUNE Match stratifies patients based on risk. Patients with medium or high risk are evaluated for biomarkers for treatment response for different drugs to determine which ongoing clinical trial is best suited for specific patients.
“NEPTUNE will allow us to compare the precision medicine-based prospective stratification versus those non-stratified classical trials,” Dr. Ju said.
Ultimately, she said, a precision medicine approach will improve patient care.
Peter Mol, PhD, PharmD, Senior Researcher in the Department of Clinical Pharmacy and Pharmacology at the University Medical Center Groningen, The Netherlands, offered his perspective as a drug regulator. Dr. Mol is a principal assessor at the Dutch Medicines Evaluation Board and a member of the Scientific Advice Working Party for the European Medicines Agency.
While regulators are sometimes seen as an obstacle to getting new treatments on the market, Dr. Mol said regulators are open to novel designs.
“We also see that drug development is getting more targeted to individual patients,” said Dr. Mol, adding that large outcome trials are not always the best way to get optimal results.
“We may want to look at more narrowly defined populations with more susceptible, sensitive types of outcomes,” he said.
Hiddo Lambers Heerspink, PhD, Clinical Pharmacologist in the Department of Clinical Pharmacy and Pharmacology at University Medical Center Groningen, examined how biomarkers such as blood pressure, A1C, cholesterol, albuminuria, and body weight, or a combination of these, can be used to personalize DKD clinical trials.
“There’s a lot of emphasis on biomarkers that predict disease progression. I think we also need biomarkers that predict a response to treatment,” Dr. Heerspink said.
To achieve this, he said blood and urine samples from clinical trials should be archived and analyzed in the future to identify biomarkers, not thrown out.
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