Anti-GH1 monoclonal antibody, clone 6G3

Context: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH1 mg/m(2) per day (similar to 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa are unknown. Objective: This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m(2) per day (similar to 0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m(2) per day. Methods: This was a longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m(2)/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m(2)/d) with 2 years of GnRHa. Results: At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m(2) per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile. Conclusions: Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m(2) per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m(2) per day.

A 66-kDa thermostable family 1 Glycosyl Hydrolase (GH1) enzyme with beta-glucosidase and beta-galactosidase activities was purified to homogeneity from the seeds of Putranjiva roxburghii belonging to Euphorbiaceae family. N-terminal and partial internal amino acid sequences showed significant resemblance to plant GH1 enzymes. Kinetic studies showed that enzyme hydrolyzed p-nitrophenyl beta-D-glucopyranoside (pNP-Glc) with higher efficiency (K-cat/K-m=2.27x10(4) M-1 s(-1)) as compared to p-nitrophenyl beta-D-galactopyranoside (pNP-Gal; K-cat/K-m= 1.15x10(4) M-1 s(-1)). The optimum pH for beta-galactosidase activity was 4.8 and 4.4 in citrate phosphate and acetate buffers respectively, while for beta-glucosidase it was 4.6 in both buffers. The activation energy was found to be 10.6 kcal/mol in the temperature range 30-65 degrees C. The enzyme showed maximum activity at 65 degrees C with half life of similar to 40 min and first-order rate constant of 0.0172 min(-1). Far-UV CD spectra of enzyme exhibited alpha, beta pattern at room temperature at pH 8.0. This thermostable enzyme with dual specificity and higher catalytic efficiency can be utilized for different commercial applications.