A research team led by Dr. Kak-Shan Shia at the National Health Research Institutes has developed a new synthetic small molecule compound named DBPR168, which holds promise as an innovative drug for preventing chemotherapy-induced peripheral neuropathy (CIPN). This drug has shown efficacy in mouse disease models, demonstrating its ability to prevent nerve tissue damage by reducing immune cell invasion into sensory nerves induced by paclitaxel and suppressing systemic inflammatory responses.
Addressing Chemotherapy Side Effects: DBPR168 Offers a New Solution
Chemotherapy remains a primary cancer treatment, but it brings severe side effects, with 60-70% of patients experiencing peripheral neuropathy during treatment. This condition leads to uncomfortable symptoms like numbness, tingling, and burning sensations in the hands and feet, which can severely impact quality of life and even force some patients to discontinue treatment. Current medications for preventing or treating CIPN only provide minimal symptom relief and are often repurposed drugs with limited effectiveness and safety concerns. Thus, there is an urgent need for new treatment options.
DBPR168: A New Mechanism, High Efficacy, and Safety with Proven Protective Power
Unlike traditional drug development that focuses on disease mechanisms, Dr. Shia's team used a phenotypic screening approach, directly observing changes in nerve cell morphology to identify compounds with neuroprotective activity from over 130,000 compounds. They then synthesized a series of derivatives and lead compounds with a complete structure-activity relationship (SAR) based on axon growth data. After structural optimization, the candidate drug DBPR168 was ultimately obtained.
In vitro tests have shown that DBPR168 effectively reduces axonal damage caused by paclitaxel and increases nerve cell survival rates by 10-15%. In mouse models, DBPR168 significantly alleviated thermal hyperalgesia and mechanical allodynia induced by paclitaxel, showing protective effects even at low doses (10 mg/kg). Electron microscopy revealed that DBPR168 effectively prevents paclitaxel-induced nerve tissue damage, including maintaining the integrity of the sciatic nerve myelin sheath, reducing inflammatory cell infiltration, and protecting mitochondria within nerve fibers. Additionally, DBPR168 exhibits an excellent therapeutic index (MTD/MED > 50), with a low minimum effective dose (MED = 10 mg/kg) and a high maximum tolerated dose (MTD > 500 mg/kg). It has also demonstrated high safety in multiple tests, including repeated dose toxicity tests and cytochrome P450 inhibition assays.
Advancing Towards Clinical Application to Enhance Patient Quality of Life
Dr. Shia stated that the team is actively negotiating technology transfers and collaborative development with domestic and international companies, aiming to submit an Investigational New Drug (IND) application to the U.S. and Taiwan FDA within the next three years. In the future, DBPR168 will primarily target cancer patients undergoing paclitaxel treatment, with the goal of effectively preventing chemotherapy-induced neuropathy, improving patient quality of life, and reducing healthcare costs.
Resource (mandarin): 告別化療副作用！新機轉藥物DBPR168 高效預防周邊神經病變
