Sickle cell disease was first described over 100 years ago, and the molecular basis of the disease was identified in 1949. Several therapies have improved the lives and well-being for some people living with the disease, and although HLA-matched bone marrow transplant in children can be curative, only a small percentage of patients can have the procedure because of the risks and because of the availability of matched donors. Despite some advances, it is estimated that approximately 100,000 Americans and millions of people worldwide are living with SCD.

Decades of basic research on sickle cell disease have laid the groundwork for novel genetic approaches for a widespread cure.  The Cure Sickle Cell Initiative will help develop the most promising next generation therapies to help find cures for those living with this devastating disease.

The National Institutes of Health (NIH) spends approximately $100 million on sickle cell disease research each year.  The National Heart, Lung, and Blood Institute (part of NIH), has supported SCD research for many years, helping to improve care for patients living with the disease. The Cure Sickle Cell Initiative builds on the legacy of NHLBI-supported research and complements the Institute’s sickle cell disease research investment, including basic, clinical, translational, and implementation science research.  Using the launch of the Initiative in September 2018, and the commitment of $7 million to jumpstart the effort, the NHLBI is continuing to advance the development of technologies that hold promise in finding genetic-based cures.  

NHLBI will continue to fund research being conducted by investigators focused on SCD, and this Initiative will help fill the gaps that cannot be covered by traditional funding methods. The Cure Sickle Cell Initiative will not replace any ongoing efforts; instead, it will complement the Institute’s broader sickle cell disease research investments.

We recognize the vital role of people living with sickle cell disease in our efforts to find new cures. Their engagement is a critical component of the Initiative and people living with SCD will work alongside researchers in not only setting the research agenda, but also in finding ways to educate and recruit patients to participate in clinical trials.  Patient representatives are involved at every level of the Initiative, and we continue to attend advocacy group meetings and conduct listening sessions and focus groups in the community to help guide our efforts.

Genetic based therapies that are being studied for sickle cell disease will require testing.  Our initial efforts are focused on determining safety in adults and once established, and if approved by the Food and Drug Administration (FDA), then we hope to begin trials in children and adolescents.

The Cure Sickle Cell Initiative aims to develop cures for all patients who have sickle cell disease and it is exploring approaches like gene transfer, gene editing, and small molecules (future approach) as potential therapies.  There are several genetic therapy approaches in early stages of development, and the Initiative is initially focusing on therapies that modify hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be used in bone marrow transplants, making cures widely available to more patients.

Genome editing (also called gene editing) is a group of technologies that gives scientists the ability to change the DNA in a cell. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed: a recent one is known as CRISPR-Cas9, which is short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated much excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to "remember" the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses' DNA. The bacteria then use Cas9 (or a similar enzyme) to cut the DNA apart, which disables the virus.

To change the DNA in a person is not currently possible, but it is possible to change the DNA in a sufficient number of some types of cells, like in some of the stem cells of the bone marrow.  The stem cells give rise to mature blood cells and this can be enough to prevent sickle cell disease.  Importantly, this does not change the DNA in the other cells of the body.  Therefore, the person who has this type of gene editing treatment still can pass the disease on to their children.  

Genome editing is of great interest in the prevention and treatment of human diseases and is being explored in a wide variety of diseases, including cystic fibrosis, hemophilia, and sickle cell disease.    

Source:  National Library of Medicine: https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting

Genome Editing with CRISPR-Cas9 Video:  https://www.youtube.com/watch?v=2pp17E4E-O8

NIH and NHLBI are funding research and collaborating with researchers to move these potential therapies into clinical trials with people living with sickle cell disease.  Within five to ten years the Initiative expects to move these genetic based therapies safely into clinical trials.  If studies meet the FDA requirements regarding safety and efficacy, then larger trials with more patients will be developed.