Imagine you are about to have your first child. You are really excited, but also very nervous. After several hours of labor, your baby is finally born. Exhausted yet exhilarated, you bring your little one home. The first few months go by, filled with joy and challenges, but then your baby starts crying nonstop. Despite your best efforts, nothing seems to soothe them.
At this point, you realize something is wrong. You rush to the hospital, where doctors conduct a battery of tests. Finally, they deliver the diagnosis: sickle cell disease. Nearly half of the children affected by this disease don’t make it to their 5th birthday. In that moment, you're faced with a terrifying reality: Is there any treatment? The answer to this question is dictated by a cruel lottery—where you are born.
Sickle cell disease (SCD) is a group of conditions in which red blood cells–which transport oxygen throughout the body— are misshapen. Red blood cells normally look like round discs; however, in sickle cell disease, they take on the form of sickles or crescent moons due to a mutation in the HBB gene, which provides instructions for producing a protein called hemoglobin (the protein which gives red blood cells their oxygen-carrying abilities). This mutant hemoglobin makes the red blood cells rigid and prone to premature death, leading to anemia. The sickle-shaped cells can also obstruct small blood vessels, resulting in severe medical complications.
So, how can we fix these cells? Pharmacological therapies have been largely ineffective and until recently, bone marrow transplants were the only available cure for SCD, a process that requires finding a suitable donor and undergoing invasive treatments for weeks. Fortunately, recent advancements in gene therapy offer a more promising option. Gene therapy involves altering an individual’s genome by replacing, deleting, or inserting genetic material. Yet, implementing such therapies is not as easy as it sounds due to high costs and the lack of representation of those most affected in clinical trials.
In her recent publication, Dr. Jennifer Adair, an associate professor in the Translational Science and Therapeutics Division at Fred Hutch, emphasizes the importance of making gene therapies accessible, acceptable and affordable, especially in low-income countries where these treatments are critically needed. Dr. Adair’s research focuses on developing gene therapies for blood stem cell cancers, including SCD. Although the disease is generally rare in North America and Europe—affecting approximately 1 in 2,000-3,000 individuals—it is much more prevalent in developing regions, affecting about 1 in 1,300 people in South America and the Caribbean, 1 in 1,000 in India, 1 in 500 in the Middle East, and 1 in 100 in Africa.
Despite the availability of gene therapies, the costs are astronomical. For instance, a gene therapy approved in the United Kingdom for SCD last year comes with a staggering price tag of $2.2 million, making it unaffordable for most people and healthcare systems even in developed countries. Moreover, clinical trials for these new gene therapies predominantly take place in developed countries and often overlook the most affected demographic—children under five years old. The focus of regulators in the U.S. and Europe has been on treating the most severely affected individuals (often adults) which skews the trial participant demographics toward older populations.
Dr. Adair and colleague propuse the transfer of "abandoned drug-development pipelines" to low-income countries. This strategy would enable local governments to invest in infrastructure for the local manufacturing of gene therapies with safety and efficacy data available, granting access to those in need. Dr. Adair believes this approach would ignite local research and development for gene therapies without imposing the stringent requirements of high-income countries.
A great example of this approach is the Drugs for Neglected Disease Initiative (DNDi), an international non-profit organization that has developed 13 treatments for 6 deadly diseases since 2003, saving millions of lives. DNDi targets diseases that are often overlooked by traditional pharmaceutical companies because they primarily affect populations in low-income regions.
In a similar vein, Dr. Adair and Dr. Cissy Kityo-Mutuluuza co-founded the Global Gene Therapy Initiative (GGTI) in 2020, aiming to facilitate the implementation of gene therapies in low- and middle-income nations and to provide information about gene therapy developments to people worldwide. Indeed, lead author and GGTI community advisory board member Evelyn Mwesigwa Harlow is the mother of a son with sickle cell disease in Uganda, a strong patient advocate with the local Ministry of Health and the donor for her child’s haploidentical bone marrow transplant which took place in India in 2020. GGTI emphasizes the importance of local manufacturing, partnerships with countries where these diseases are prevalent, and inclusive clinical trials to make gene therapies more affordable and effective worldwide.
GGTI collaborates with a global network of public and private partners, including universities, research institutes, pharmaceutical companies, governments, and patients to leverage existing expertise and resources. GGTI meets weekly, and anyone can join to learn more about gene therapies and how they are changing the landscape of gene therapy. Check out its website!
Evelyn and Dr. Adair poignantly recall Elizabeth Merab’s words: “The only thing more difficult than hearing that you have a disease for which there are no cures is to hear that you have a disease for which cures are available, but they are not available to you.” Merab, a member of GGTI’s international advisory board, tragically passed away due to complications from SCD one year prior to this publication at just 31 years old.
Dr. Adair concludes, “Everyone with a devastating disease should have access to a cure when one exists. True progress will only occur when low-income countries are integrated into the development of gene therapies.”
GGTI is funded by an Innovation Award from the Bill & Melinda Gates Foundation, and in-kind support from Caring Cross. Dr. Adair is the Fleischauer Family Endowed Chair in Gene Therapy Translation, which also supports GGTI network infrastructure.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Jennifer Adair contributed to this work.
Harlow EM, Adair JE. Make gene therapies more available by manufacturing them in lower-income nations. Nature. 2024 Jul;631(8021):502-504. doi: 10.1038/d41586-024-02310-y.