HIV and sickle cell disease are two illnesses that disproportionately affect people of African descent. They are also two illnesses for which scientists are actively hunting for a cure using new gene editing technologies.
Now, the National Institutes of Health (NIH) is teaming up with the Bill and Melinda Gates Foundation and the World Health Organization (WHO) in an effort to develop gene-based cures for HIV and sickle cell disease. The NIH and the Gates Foundation have devoted $100 million each to this initiative.
Unlike existing therapies, gene therapy is intended to cure disease rather than just treat it. Although there are a handful of Food and Drug Administration (FDA)-approved gene therapies on the market for other illnesses, finding a gene-editing cure for HIV and sickle cell disease will take years, if not decades.
The first phase of the initiative -- slated to span at least four years -- will be a scientific exploration of the best curative approach for each illness. The collaboration hopes to move into human trials within the decade.
Leaders from the NIH, the Gates Foundation, and WHO emphasized that any cures resulting from this collaboration will be accessible for anyone who needs them.
The goal is "to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries," said NIH Director Francis S. Collins, M.D., Ph.D., according to prepared remarks. "We aim to go big or go home."
Existing gene therapies tend to be boutique treatments -- one recently approved therapy famously costs $2.1 million. And previous U.S. government-sponsored research collaborations have resulted in transformative medicines that are then commercialized by pharmaceutical companies and priced out of reach for many patients.
Among the world's 38 million people living with HIV, 95% live in the developing world and 67% live in sub-Saharan Africa. Meanwhile, in sub-Saharan Africa, sickle cell disease is the underlying cause of about one in every 12 infant deaths.
During the first phase of collaboration, NIH and Gates Foundation scientists will attempt to identify potential gene therapy cures for HIV and sickle cell disease. Specifically, the challenge will be to develop new ways of delivering treatment to the correct cells inside the body.
For sickle cell disease, this means targeting cells that contain a genetic mutation that underpins the disease. For HIV, it means trying to target the ever-elusive viral reservoir.
According to Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of the NIH, the only way to ensure that a gene editing cure for HIV is practical and affordable is to ensure that the resulting therapy is delivered in vivo, meaning inside the body.
Some existing gene therapies are delivered ex vivo, meaning that scientists remove existing cells from a patient's body, edit them in a laboratory, and re-infuse the edited cell material back inside the patient. This treatment approach is expensive and impractical for low-income settings, Fauci pointed out.
An in-vivo approach to gene editing is scientifically feasible. In 2017, the FDA approved the first-ever in-vivo gene therapy, for a rare condition that can cause blindness. But for HIV, an in-vivo approach to HIV gene therapy is a long way off.
"It is a very high-risk, aspirational approach," Fauci said. "We felt the only way we could make that available and feasible and affordable to those who need it in the developing world is to have a very specific component … directed at in-vivo gene-based therapy."
It's a tall scientific hurdle for the NIH and its collaborators, which is why the organizations have set up a steering committee that will oversee all experiments proposed as part of the initial $200 million in funding. The steering committee will ensure efforts are streamlined among the various scientific groups that will be working on the initiative.
Once those experiments yield potential cures, the organizations will work with the WHO and African partners to roll out studies in humans to see if the results hold up in patients living in areas with the highest burden of disease.
Unlike other NIH-sponsored cure research, Fauci said, "this specific program clearly has a very high-risk, certainly high-reward goal to it that is a bit different to anything we have done."