CLT-001: Purified Stem Cells to Treat Sickle Cell Disease

Sickle Cell Disease: An Overview

Sickle Cell Disease (SCD) is an inherited blood disorder characterized by chronic anemia, progressive organ damage, and periodic crises of moderate to severe pain. The root cause of SCD is a genetic defect in the hemoglobin, a protein in red blood cells that carries oxygen. This defect causes red blood cells to deform, or “sickle”, resulting in red blood cells getting stuck in blood vessels, blocking the flow of oxygen to organs and tissue. Additionally, these defective red blood cells do not live as long as healthy red blood cells, leaving the victim with anemia, a chronic shortage of red blood cells. Strokes, lung clots, and other complications lead to lengthy hospital stays. Despite advances in the treatment of SCD, the lifespan of most patients is reduced by almost 20 years.

SCD affects millions of people throughout the world. In the U.S. it affects approximately 75,000 people, most being of African descent. And 2 million Americans, about 1 in 12 African Americans, carry the sickle cell trait.

For more information on sickle cell disease, please see the American Sickle Cell Anemia Association or the Sickle Cell Disease Association of America.

Current Treatments

Current treatment for SCD is designed to address the symptoms of disease. Narcotic pain killers are used to treat the severe pain that often results from the tissue death caused by sickle cells blocking blood flow to organs. Drugs are used to stimulate production of additional blood cells. Transfusions are used to treat the anemia that results from the early death of sickle cells, and to dilute the sickle cells with normal red blood cells.

Stem Cell Transplant Cure for SCD

The theory is simple: replace the blood-forming system that produces sickle red blood cells with one from a healthy donor that produces healthy red blood cells. Stem cell transplants have been used for SCD in a limited fashion for about a decade, and the cure rate is about 85%.

However, there are two major barriers to stem cell transplants to treat SCD: 1) the risk of serious illness associated with donor-to-patient stem cell transplant; and 2) the lack of appropriate donors. For these reasons, only about 300 of these transplants have been performed to date.

All donor-to-patient stem cell transplants use material which contains donor T-cells. These donor T-cells react to the patient's body as "foreign", causing graft-versus-host disease (GVHD). GVHD is a significant cause of illness and even death in stem cell transplants, and is generally avoided by using a donor as closely matched to the patient as possible, and by appropriate care after the transplant to quickly address symptoms of GVHD when they arise.

Another problem with stem cell transplant for SCD is a lack of donors. Usually, a patient's brother or sister who is a close genetic match to the patient is the preferred donor. Using closely matched donors reduces the risk of GVHD: the closer the donor cells are to the patient's cells, the less severe the immune reaction is likely to be.

In the normal population, a patient has about a 30% chance of having a matched sibling donor. However, SCD is a genetic disease, passed on from parents to children. A brother or sister who is a close match to the patient is very likely to also have SCD, making them inappropriate as a donor. The chance that an SCD patient has a matched sibling donor is less than 15%.

How Cellerant Fights Sickle Cell Disease

CLT-001 transplants should lower the risk of GVHD since CLT-001 does not contain T cells. CLT-001 may also reduce the level of matching required for these transplants, making them more widely available.