GDNF gene therapy for alcohol use disorder in male non-human primates
Alcohol use disorder is a lifelong disease often characterized by episodes of abstinence and relapses with limited therapies that target the underlying brain circuitry involved. In this study, the authors target the neuroadaptations of dysfunction of reward circuitry that occur in the ventral tegmental area (VTA). Human glial-derived neurotrophic factor (hGDNF) enhances dopaminergic neuron function, and the authors conducted gene therapy delivering a vector carrying the gene into the VTA of rhesus monkeys who had previously had chronic alcohol self-administration. The treated monkeys demonstrated increases in GDNF protein and dopamine, as well as significant decreases in alcohol intake sustained for up to a year. While additional research is needed, this study demonstrates GDNF as a potential target for treatment of alcohol use disorder.
Buprenorphine Out-of-Pocket Costs and Discontinuation in Privately Insured Adults With Opioid Use Disorder
JAMA Internal Medicine
This study considered the link between out-of-pocket costs for an initial buprenorphine prescription and buprenorphine discontinuation within a 1-year period among commercially insured U.S. adults. Higher daily medication out-of-pocket costs were associated with treatment discontinuation. Generic film and tablet, as well as branded (Suboxone) tablets, also increased risk of discontinuation compared with branded film. Median time to treatment discontinuation was 64 days. The addition of buprenorphine to the Patient Protection and Affordable Care Act’s preventive drug list is but one consideration to ease the impact of the OUD crisis.
Prospects for Pain 🔓
The New England Journal of Medicine
This is a summary of an interview with the lead author and details from the accompanying article and editorial. Some types of pain have proven resistant to all available medications. New sodium-channel blockers offer promise for efficacious treatment. The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. This clinical study in humans shows that targeting a peripheral sodium channel can reduce pain in human subjects without significant adverse side effects.