Leucine-rich repeat kinase 2 (LRRK2) inhibitors for Parkinson's disease: a patent review of the literature to date.

INTRODUCTION: Nearly two decades after leucine rich repeat kinase 2 (LRRK2) was discovered as a genetic determinant of Parkinson's disease (PD), LRRK2 has emerged a priority therapeutic target in PD and inhibition of its activity is hypothesized to be beneficial. AREAS COVERED: LRRK2 targeting agents, in particular kinase inhibitors and agents reducing LRRK2 expression show promise in model systems and have progressed to phase I and phase II clinical testing for PD. Several additional targeting strategies for LRRK2 are emerging, based on promoting specific 'healthy' LRRK2 quaternary structures, heteromeric complexes and conformations. EXPERT OPINION: It can be expected that LRRK2 targeting strategies may proceed to phase III clinical testing for PD in the next five years, allowing the field to discover the real clinical value of LRRK2 targeting strategies.

The Safety of Medications used to Treat Peripheral Neuropathic Pain, Part 2 (Opioids, Cannabinoids and Other Drugs): review of Double-Blind, Placebo-Controlled, Randomized Clinical Trials.

INTRODUCTION: Peripheral neuropathic pain is a disabling condition for patients and a challenge for physicians. Although many drugs have been assessed in scientific studies, few have demonstrated clear clinical efficacy against neuropathic pain. Moreover, the paucity of data regarding their safety raises the question of the benefit-risk ratio when used in patients experiencing peripheral neuropathies. AREAS COVERED: We conducted a review of double-blind, placebo-controlled, randomized clinical trials to assess the safety of medications used to treat peripheral neuropathic pain. This second review was focused on opioids, cannabinoids, and other medications. The aim was to provide an overview of the treatment-emergent adverse events (TEAEs) (≥10%) and the serious adverse effects described in clinical trials. EXPERT OPINION: Opioids and cannabinoids had significantly more TEAEs than placebos. Locally administered analgesics, such as capsaicin, lidocaine, botulinum toxin A seemed to have the most acceptable safety with only local adverse effects. The results for NMDA antagonists were inconclusive since no safety report was available. Less than half of the studies included presented a good description of TEAEs that included a statistical comparison versus a placebo group. Major methodological improvements must be made to ameliorate the assessment of medication safety in future clinical trials.