Mouse Anti-Galactomannan monoclonal antibody, clone CCRC-M70

Water-soluble polysaccharides and pectinic substances from seed pods of Crotalaria alata L. (Uzbekistan) and Crotalaria sp. (India) were studied. The water-soluble polysaccharides were found to dominate over pectinic substances. Galactomannan GM-SP with a Man:Gal ratio of 4.4:1 was isolated from Crotalaria sp. seed pods. Its main chain consisted of 1,4-beta-bound polymannans with 1,6-alpha-bound galactopyranose side residues. Sulfated derivatives of galactomannan from C. alata were prepared. The supramolecular structures of the galactomannan and its sulfated derivative were studied using electron microscopy. The galactomannan sulfated derivative exhibited anticoagulant activity.

BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. MethodsIn a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 mu g once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo(2)) at week 24. ResultsIn total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo(2) data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo(2) at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P=0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P=0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. ConclusionsIn patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.) Patients with autoimmune pulmonary alveolar proteinosis received inhaled molgramostim or matching placebo for 24 weeks. Patients receiving molgramostim had greater improvement in pulmonary gas transfer and alleviation of symptoms than those receiving placebo.