Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial.

AIM: To assess the efficacy, safety and tolerability of beloranib treatment for obesity. METHODS: This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4 mg) or placebo, administered subcutaneously, for 12 weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. RESULTS: At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5 ± 0.5, -6.9 ± 0.6 and -10.9 ± 1.1 kg for the 0.6, 1.2 and 2.4 mg beloranib doses, respectively, compared with -0.4 ± 0.4 kg with placebo (all p < 0.0001 vs placebo). Weight loss with beloranib was associated with corresponding reductions in waist circumference and body fat mass, as well as improvements in lipids, high-sensitivity C-reactive protein and blood pressure. Sleep disturbance and gastrointestinal adverse events were more common with beloranib than with placebo; these were generally mild to moderate, transient and dose-related, and led to more early study withdrawals in participants in the group with the highest dose of beloranib. CONCLUSIONS: In this 12-week phase II study, beloranib produced clinically and statistically significant weight loss and corresponding improvements in cardiometabolic risk factors. Beloranib appeared safe, and the 0.6 and 1.2 mg doses were generally well tolerated. The 2.4 mg dose was associated with increased sleep latency and mild to moderate gastrointestinal adverse events over the first month of treatment. These findings represent a novel mechanism for producing clinically meaningful weight loss.

Refined localisation of the genes for nebulin and titin on chromosome 2q allows the assignment of nebulin as a candidate gene for autosomal recessive nemaline myopathy.

A locus for autosomal recessive nemaline myopathy (NEM2) has been assigned by linkage analysis to a 13-cM region between the markers D2S150 and D2S142 on 2q21.2-q22. The genes for the giant muscle proteins nebulin and titin have previously been assigned by FISH to 2q24.1-q24.2 and 2q31, respectively. By using radiation hybrid mapping, we have reassigned the nebulin gene close to the microsatellite marker D2S2236 on 2q22 and the titin gene to the vicinity of the markers D2S384 and D2S364 on 2q24.3. The genomic orientation of the nebulin gene was determined as 5'-3' and of TTN as 3'-5' from the centromere. We conclude that the nebulin gene resides within the candidate region for NEM2 on the long arm of chromosome 2, while the titin gene is located outside this region.