Novel myostatin-specific antibody enhances muscle strength in muscle disease models.

Myostatin, a member of the transforming growth factor-ß superfamily, is an attractive target for muscle disease therapy because of its role as a negative regulator of muscle growth and strength. Here, we describe a novel antibody therapeutic approach that maximizes the potential of myostatin-targeted therapy. We generated an antibody, GYM329, that specifically binds the latent form of myostatin and inhibits its activation. Additionally, via "sweeping antibody technology", GYM329 reduces or "sweeps" myostatin in the muscle and plasma. Compared with conventional anti-myostatin agents, GYM329 and its surrogate antibody exhibit superior muscle strength-improvement effects in three different mouse disease models. We also demonstrate that the superior efficacy of GYM329 is due to its myostatin specificity and sweeping capability. Furthermore, we show that a GYM329 surrogate increases muscle mass in normal cynomolgus monkeys without any obvious toxicity. Our findings indicate the potential of GYM329 to improve muscle strength in patients with muscular disorders.

Introduction of arteriovenous grafts with graft insertion anastomosis for hemodialysis access.

OBJECTIVE: An arteriovenous bridging graft is a viable option for patients with compromised arteries or veins because of advanced age or diabetes. Arteriovenous graft with graft insertion anastomosis (AVGI) is the novel technique for graft-vein anastomosis where the prosthesis is inserted into the vein, and the anastomosis is performed on the surface of the prosthesis. This study assessed the short-term and long-term results of AVGI to clarify the efficacy of this technique. METHODS: Between 2010 and 2015, AVGI was performed in graft-vein anastomosis of prosthetic forearm loop access. Characteristics and level of complications were assessed. To evaluate the long-term results, functional graft patency and frequency of percutaneous transluminal angioplasty were examined. RESULTS: The study comprised 58 patients. There were no deaths related to the surgery. The time of hemostasis after AVGI was recorded at 0 seconds because no bleeding from the suture holes was seen. At 1, 2, and 3 years, primary patency were 45.1% ± 7.5%, 23.1% ± 7.5%, and 23.1% ± 7.5%, respectively, and assisted primary patency rates were 59.4% ± 7.2%, 50.8% ± 7.6%, and 50.8% ± 7.6%, respectively. Secondary patency rates at 4 and 5 years were 100% ± 0% and 94.1% ± 5.7%, respectively. The frequency of percutaneous balloon angioplasty to maintain the patency was 1.61 ± 0.53 times per year. Graft infection occurred in four patients (6.9%). CONCLUSIONS: AVGI is an advantageous technique for graft vein anastomosis in an arteriovenous bridging graft in both the short-term and long-term.

Solute-free versus electrolyte-free water clearance in the analysis of osmoregulation.

BACKGROUND: Although attention has recently focused on electrolyte-free water clearance (E-CH2O) as a replacement for solute-free water clearance (CH2O), especially from the viewpoint of plasma sodium regulation, a thorough comparison of the two has yet to be conducted. METHODS: CH2O and E-CH2O were systematically compared in normal subjects in different diuretic stages, including furosemide-induced solute diuresis, and in patients with renal disease. RESULTS: The normal renal ability to conserve free water based on E-CH2O was only 41% of that based on CH2O. E-CH2O remained positive until the urinary osmolality exceeded 500 mosm/kg H2O, markedly different from the 300 mosm/kg H2O for CH2O. The difference between E-CH2O and CH2O could ultimately be attributed to urea osmolar clearance, i.e., urea excretion rate/plasma osmolality, which accounted for about 40% of the osmolar clearance. CH2O underestimated the free water clearance by about 1 ml/min on average at all diuretic stages. CONCLUSIONS: E-CH2O is a more correct parameter than CH2O with regard to the regulation of both plasma sodium and plasma osmolality. However, there is the opinion that the concept of E-CH2O is difficult to understand and that E-CH2O is still not a generally accepted parameter. It is expected that the results of the present study will lead to more general acceptance.