Laboratory Developed Test (LDT) to Support Clinical Evaluation of a Drug for Painful Diabetic Neuropathy

Abstract Chronic pain, especially neuropathic pain that affects the normal functioning of nerves, represents an unmet medical need, because a large percentage of patients with neuropathic pain conditions do not receive adequate pain relief resulting in suffering and reduced quality of life. Inflammation plays an important role in various neuropathic pain conditions, including Painful Diabetic Neuropathy (PDN). Chemokines and their receptors are thought to play a critical role in inflammation-related painful conditions; and past efforts in the pharmaceutical industry have led to the development of compounds that modulate individual components of the chemokine- receptor network. One of the drug targets is a specific chemokine receptor, because of its role in modulating neuropathic pain conditions. Previously, a selective antagonist for this receptor was studied in a number of clinical trials, including several Phase II clinical trials, one of which aimed at neuropathic pain conditions in PDN. These clinical trials demonstrated the favorable safety and tolerability profiles of this drug in humans. However, patients' genetic profiles were not taken into account, leading to less favorable results from the clinical studies. We obtained access to the clinical dataset package, blood samples collected during clinical studies, and the potential to continue developing the compound. Through our preliminary studies, we identified this receptor’s gene expression levels as an important biomarker for predicting the clinical efficacy of the drug in treating painful diabetic neuropathy (PDN). This suggests that the gene expression levels may be used as an enrollment inclusion criterion, to enrich the PDN patient population most likely to respond to the drug treatment in clinical studies. For this SBIR grant application, we propose to develop a Laboratory Developed Test (LDT), to be used as an enrollment inclusion criterion, in the clinical development of this drug as a therapeutic for PDN. Our overall rationale for the LDT development is to follow a "test and confirm" strategy. The proposed studies in this SBIR grant are designed to implement this relatively straightforward strategy: we will design a qPCR assay as the LDT to measure the specific gene mRNA levels, and then use it to measure the receptor as the biomarker with a set of clinical trial samples.