Is 5-hydroxymethyl-2-furfural (5-HMF), a naturally occurring small molecule. Through direct binding to hemoglobin, Aes-103 prevents polymerization and ultimately the formation of rigid, sickled RBCs. Aes-103 specifically targets cell sickling, the root cause of the disease and is expected to significantly decrease its complications and increase the life expectancy of patients-103 http://grantome.com/grant/NIH/R01-FD004815-01A1
2. GBT 440
GBT440 (Global Blood Therapeutics) — a novel, oral small molecule hemoglobin modifier — increases hemoglobin oxygen affinity.
Phase I/II trials concluded.
Statins (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) have been shown to improve vascular function, independent of their lipid-lowering properties, by suppressing the inflammatory response to endothelial injury and restoring nitric oxide (NO) bioavailability. We previously documented a reduction in plasma biomarkers of inflammation and endothelial adhesion in SCD patients treated with short-term simvastatin. The objective of this study was to evaluate the potential clinical efficacy of simvastatin in reducing the frequency of vaso-occlusive pain in SCD.
Selexys is currently conducting a Phase II clinical trial in patients with sickle cell disease. The trial (called the SUSTAIN study) is being performed to assess the safety and potential impact of SelG1 in sickle cell disease patients with pain crises. SelG1 prevents various cells in the bloodstream from sticking together. This trial is testing whether inhibition of these cell-cell interactions with SelG1 will prevent small blood vessels from becoming blocked and therefore reduce the occurrence and severity of pain crises. Other effects of SelG1 will also be evaluated including the safety of the drug and how long it stays in the blood stream.
The SUSTAIN study is currently ongoing, but is no longer recruiting participants. However, if you would like to find out more about the SUSTAIN study, please visithttp://clinicaltrials.gov/ct2/show/NCT01895361.
Vepoloxamer (MST-188), an investigational agent, is purified poloxamer 188, a nonionic, block copolymer comprised of a central linear chain of hydrophobic polyoxypropylene flanked on both sides by linear hydrophilic polyoxyethylene chains. Substantial research has demonstrated that poloxamer 188 has cytoprotective and hemorrheologic properties and inhibits inflammatory processes and thrombosis. Currently in Phase 3 clinical trials with results due in Q2 2016.
Sevuparin is a new chemically modified heparin with low anticoagulant activity. Heparins generally have multiple biological properties, including antithrombin III-dependent inhibition of thrombin as well as blockade of P-selectin-mediated adhesion. Selectins have been shown to contribute to both sickle red cell (SS RBC) and neutrophil (PMN) adhesion in vitroand in mice with sickle cell disease (SCD). Sickle mice lacking both P- and E-selectins are relatively resistant to tumor necrosis factor-α (TNFα)-induced vaso-occlusion. We therefore theorized that sevuparin would show activity in inhibiting the selectin-dependent adhesion of red cells and leukocytes seen in the context of SCD, with the potential to decrease vaso-occlusion at a low level of anti-coagulation.
Commenced Phase two clinical trials in October 2015 and currently recruiting in the Netherlands, Turkey, Lebanon and Bahrain.
Proposed Rx for vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) in sickle cell disease.
NVX-508 is designed to deliver oxygen to the diseased tissues in patients with sickle cell disease.
Preliminary data has shown great potential efficacy in treatment of Acute Chest Syndrome in transgenic Sickle Cell Disease mice, which is an acknowledged model for complication of the human disease. Mechanistically, the product should also have efficacy in vaso-occlusive painful crisis, which is the hallmark of this human disorder.
The compound is a synthetic glycomimetic molecule, which was rationally designed to inhibit all three selectin types (a pan-selectin inhibitor). Selectins are glycoprotein cell adhesion molecules implicated in inflammatory processes. To achieve adequate therapeutic activity in certain inflammatory disorders, inhibition of all three selectin types (E-selectin, L-selectin and P-selectin) may be required. We therefore believe that rivipansel’s ability to inhibit all selectins will provide distinct advantages over other approaches that target only one selectin, or which are so broadly active as to be non-specific.
Currently recruiting for Phase 3 clinical trials.