Medicines to Improve Blood Flow

Sickle cell disease is a genetic condition that affects the shape of red blood cells (RBCs) due to the presence of an abnormal form of hemoglobin, the protein that carries oxygen to various cells and tissues in the body. The RBCs become rigid and S- (sickle)-shaped, which hinders their movement inside blood vessels.

The U.S. Food and Drug Administration (FDA) has approved therapies including stem cell transplant, Endari, and Oxbryta to treat sickle cell disease. Several experimental therapies are currently being investigated, some of which focus on improving blood flow. These are summarized below.


Olinciguat (IW-1701) is an investigational soluble guanylate cyclase (sGC) stimulation therapy developed by Cyclerion Therapeutics. The FDA granted it orphan drug status in 2018.

In sickle cell disease, the sickle-shaped RBCs rupture and release hemoglobin and an enzyme called arginase into the blood. These combine with nitric oxide (NO), a signaling molecule involved in promoting blood flow, lowering its overall availability and leading to lower sGC production.

Olinciguat stimulates sGC production that results in enhanced production of a signaling molecule called cyclic guanosine monophosphate (cGMP), an important regulator of blood vessel relaxation.

Phase 1 clinical trials of single-dose (NCT02572349) and multiple ascending doses (NCT02792998) of Olinciguat in sickle cell disease patients showed good tolerance, increased cGMP levels, decreased blood pressure, and low clearance by the kidneys.


Riociguat is a guanylate cyclase stimulant that is marketed by Bayer under the name Adempas in the U.S. Riociguat increases the activity of the enzyme guanylate cyclase, which upon activation by nitric oxide (NO) produces cGMP.

Increased availability of cGMP in blood vessels within the lungs relaxes blood pressure, promotes heart function, and helps patients be more active.

Riociguat is being studied in a Phase 2 clinical trial (NCT02633397) for its effectiveness in treating pulmonary hypertension in sickle cell disease patients.


Ticagrelor is an approved blood thinner made by AstraZeneca and marketed as Brilinta in the U.S. It’s prescribed for people who have had heart attacks to reduce the risk of developing blood clots and having a stroke or another heart attack.

Ticagrelor is being investigated in sickle cell disease because of its ability to reduce blood vessel blockages.

In people with sickle cell disease, RBCs often stick to the inner lining of the blood vessels and clump together, leading to episodes of acute pain known as vaso-occlusive crises (VOC). Sickle cell disease patients show more activated platelets than normal, which can further promote adhesiveness of the RBCs to the blood vessel walls leading to blockage.

Ticagrelor blocks the activity of a receptor called P2Y12 that is important for blood clotting, resulting in less platelet clumping and blood vessel blockage.


Last updated: Feb. 17, 2020


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