Date: 2016-09-14
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Physiological Reports
Company: Global Blood Therapeutics (USA - CA)
Product: GBT440
Action
mechanism: hemoglobin modifier. GBT440 is a novel small molecule that binds specifically to hemoglobin (the oxygen-carrying protein in red blood cells) and is designed to inhibit sickle hemoglobin (HbS) polymer formation.
Disease: hypoxemic pulmonary disorders, including idiopathic pulmonary fibrosis
Therapeutic area: Lung diseases - Respiratory diseases - Rare diseases
Country:
Trial details:
Latest
news: * On September 14, 2016, Global Blood Therapeutics announced publication of preclinical data supporting the development of GBT440 for the treatment of hypoxemic pulmonary disorders, including idiopathic pulmonary fibrosis (IPF), in Physiological Reports. To date, GBT has established preclinical proof of concept for GBT1118, a hemoglobin modifier and analog of GBT440, in three different animal models of hypoxia. Data from these models support the potential beneficial effects of hemoglobin modification as a promising therapeutic strategy to treat hypoxemia (abnormally low levels of oxygen in the blood) associated with chronic fibrotic lung disorders, such as IPF. The published study is the first to suggest that hemoglobin modifiers, such as GBT440, have the potential to increase oxygen uptake in the lungs, resulting in improved oxygen delivery to tissues. To assess whether pharmacological modification of hemoglobin-oxygen affinity could improve hypoxemia associated with lung fibrosis, researchers evaluated GBT1118 in a bleomycin-induced mouse model of hypoxemia and fibrosis. After pulmonary fibrosis and hypoxemia were induced, GBT1118 was administered for eight days. Hypoxemia was determined by monitoring arterial oxygen saturation, while the severity of pulmonary fibrosis was assessed by histopathologic evaluation and determination of collagen and leukocyte levels in bronchoalveolar lavage fluid (BALF). Treatment with GBT1118 restored arterial oxygen saturation to near normal levels. It also reduced collagen levels in BALF and inflammatory cell infiltration, and reduced lung fibrosis by approximately 50 percent.
