The pace of biomarker development is accelerating as investigators report new studies on cancer, diabetes, Alzheimer disease, and other conditions in which the evaluation and isolation of workable markers is prominently featured. CHI’s “ADAPT” meeting, to be held later this month, will profile various new strategies being developed by both the academic and private sectors.
Wei Zheng, Ph.D., leader of the R&D immunoassay group at EMD Chemicals, is overseeing a program to develop biomarker immunoassays to monitor drug-induced toxicity, including kidney damage.
Although immunohistochemistry has traditionally been looked upon as the gold standard for these studies, this approach is slow and cannot be adapted to multiplexing. “One of the principle reasons for drugs failing during development is because of organ toxicity,” says Dr. Zheng. “This results in proteins being liberated into the serum and urine in abnormal amounts. These proteins can serve as biomarkers of adverse response to drugs, as well as disease states.”
Through collaborative programs with Rules-Based Medicine (RBM), the EMD group has released panels for the profiling of human renal impairment and renal toxicity. These urinary biomarker based products fit the FDA and EMEA guidelines for assessment of drug-induced kidney damage in rats.
Although the FDA has not yet approved kidney toxicity biomarker tests, the industry is clearly moving in that direction, according to Dr. Zheng. “We see this trend, not only for drug-induced organ damage but also for biomarkers for disease states affecting organ function.”
The group recently performed a screen for potential protein biomarkers in relation to kidney toxicity/damage on a set of urine and plasma samples from patients with documented renal damage. Multiplexed immunoassays were used to quantify protein analytes and standard blood and urine chemistries were also measured.
Additionally, Dr. Zheng is directing efforts to move forward with the multiplexed analysis of organ and cellular toxicity. Diseases thought to involve compromised oxidative phosphorylation include diabetes, Parkinson and Alzheimer diseases, cancer, and the aging process itself.
Good biomarkers allow Dr. Zheng to follow the mantra, “fail early, fail fast.” With robust, multiplexible biomarkers, EMD can detect bad drugs early and kill them before they move into costly large animal studies and clinical trials. “Recognizing the severe liability that toxicity presents, we can modify the structure of the candidate molecule and then rapidly reassess its performance.”