Research on Sickle Cell Disease
Reviewed by: HU Medical Review Board | Last reviewed: February 2023 | Last updated: March 2023
Sickle cell disease (SCD) researchers expect powerful new treatments to come in the next few years. About 30 drugs are currently in late-stage clinical trials to treat SCD. These drugs work in different ways to reduce the effects of abnormal sickle hemoglobin.1
Talk to your doctor to discuss whether participating in a clinical trial is right for you. Participation and funding in SCD trials remains challenging, with many trials ending early because of low enrollment. However, the SCD community is eager to work with doctors to find new treatments. With all of the current work being done, the future of SCD treatment looks promising.
What medicines are in clinical trials?
About 30 drugs are in clinical trials to treat SCD. Most of these drugs were developed for other purposes and are being evaluated in SCD. These drugs work in different ways to reduce complications of SCD.2
Drugs that increase hemoglobin F
Fetal hemoglobin (hemoglobin) F is normally only present in newborns and protects them from complications of SCD. Increasing the amount of hemoglobin F in older children and adults can reduce complications of SCD. This is how hydroxyurea works. Drugs that increase hemoglobin F in clinical trials include:2,3
Decitabine has completed a phase II trial for SCD, while pomalidomide has completed phase I. Panobinostat is currently in phase I.
Drugs that prevent blood cell sticking
Sickle red blood cells stick to each other and to the walls of blood vessels. This blocks blood flow. Drugs that reduce blood cell sticking can reduce complications of SCD. This is how crizanlizumab (Adakveo) works. Drugs in clinical trials that reduce sticking include:2
- Intravenous Ig
All of these drugs are either in phase II trials or have completed phase II trials.
Drugs that reduce inflammation
Inflammation is the body’s way of fighting infections and injuries. The body releases chemicals that trigger a response from the immune system. People with SCD often have chronic inflammation, which contributes to blocked blood flow. Drugs that reduce inflammation in clinical trials for SCD include:2-4
- N-acetyl cysteine
N-acetyl cysteine is in phase III trials for SCD. The rest of these drugs have either completed phase I or II.
Drugs that widen blood vessels
Sickle cells burst easily and release their contents, including hemoglobin, into the blood. Free hemoglobin in the blood blocks a chemical called nitric oxide. Nitric oxide helps to widen blood vessels. Because of low nitric oxide levels, people with SCD often have blood vessels that are narrower and more vulnerable to blockage. Drugs that widen blood vessels in clinical trials for SCD include:2,4
- Inhaled nitric oxide
- PF 04447943
All of these drugs are in either phase I or II clinical trials for SCD.
Supplements and other drugs
Some supplements are being studied for different aspects of SCD. These include:2
- Cholecalciferol (Vitamin D3)
- Niacin (Vitamin B3)
Many other drugs will continue to enter clinical trials for SCD. For example, researchers found 9 drugs that increase hemoglobin F levels in laboratory experiments. These drugs are already approved by the FDA for other conditions and could be good candidates to enter trials as SCD drugs.5,6
What is gene therapy?
A gene is a piece of DNA that contains information to make a specific protein. Genes are units that are passed down from parents to children. Mutations in the DNA lead to proteins that do not work properly. This can cause genetic disorders, including sickle cell disease.7
Gene therapy involves fixing an abnormal gene or adding a new gene. Researchers take blood or bone marrow and modify the stem cells in a laboratory using gene therapy techniques. The modified cells are then injected back into the blood.4,7
Genetic therapies are in development to treat or cure inherited disorders, cancers, and infections. Newer and better gene therapy techniques, like CRISPR technology, have made it a more promising treatment method.8
How has gene therapy been researched in sickle cell disease?
SCD is caused by a mutation in the HBB gene, which contains information for cells to make part of hemoglobin. Mutated hemoglobin sticks together inside red blood cells, causing them to become sickled and unable to easily pass through blood vessels.8
Gene therapy may be a potential cure for SCD. One strategy is to add a normal HBB gene into stem cells. This would allow them to produce normal hemoglobin and red blood cells. Another strategy is to alter a different gene to boost production of hemoglobin F.9
Gene therapy has had promising initial results in the lab and in case studies. Several phase I and II trials are currently underway to test different gene therapy methods in SCD.10-13