Identification of prophylactic drugs for oxaliplatin-induced peripheral neuropathy using big data.

BACKGROUND: Drug repositioning is a cost-effective method to identify novel disease indications for approved drugs; it requires a shorter developmental period than conventional drug discovery methods. We aimed to identify prophylactic drugs for oxaliplatin-induced peripheral neuropathy by drug repositioning using data from large-scale medical information and life science information databases. METHODS: Herein, we analyzed the reported data between 2007 and 2017 retrieved from the FDA's database of spontaneous adverse event reports (FAERS) and the LINCS database provided by the National Institute of Health. The efficacy of the drug candidates for oxaliplatin-induced peripheral neuropathy obtained from the database analysis was examined using a rat model of peripheral neuropathy. Additionally, we compared the incidence of peripheral neuropathy in patients who received oxaliplatin at the Tokushima University Hospital, Japan. The effects of statins on the animal model were examined in six-week-old male Sprague-Dawley rats and seven or eight-week-old male BALB/C mice. Retrospective medical chart review included clinical data from Tokushima University Hospital from April 2009 to March 2018. RESULTS: Simvastatin, indicated for dyslipidemia, significantly reduced the severity of peripheral neuropathy and oxaliplatin-induced hyperalgesia. In the nerve tissue of model rats, the mRNA expression of Gstm1 increased with statin administration. A retrospective medical chart review using clinical data revealed that the incidence of peripheral neuropathy decreased with statin use. CONCLUSION AND RELEVANCE: Thus, drug repositioning using data from large-scale basic and clinical databases enables the discovery of new indications for approved drugs with a high probability of success.

[Quantification of gait using insole type foot pressure monitor : clinical application for chronic hemiplegia].

Home-based stroke hemiplegia patients tend to fall easily. Poor toe clearance is reported to be one of the causes of falling, although there are many other related factors. We developed a low-priced insole type portable foot pressure measurement device, and measured the foot pressure distribution and the foot pressure-time curve of 20 chronic hemiplegia patients and compared them with 36 healthy controls. We also analyzed the outdoor gait of a chronic hemiplegia patient on flat ground, on rough terrain, walking up stairs and on a downward slope. The result was that the load rate of the unaffected heel was significantly increased in hemiplegic gait, and there was a significant negative correlation between the affected side stance phase rate and gait time for 10 m distance (r = -0.73, P < 0.01). The primary role of the unaffected side and the poor toe clearance on the affected side were assured in the uneven ground gait, and it was suggested that chronic hemiplegia patients tend to be highly dependent on their unaffected side during indoor and outdoor gait.