NIH director Francis S. Collins, MD, PhD.

The NIH and the Bill and Melinda Gates Foundation said they are committing a total $200 million toward developing gene therapies for sickle cell disease (SCD) and HIV that will be affordable in areas of the world hardest hit by the diseases.

The agency and Gates Foundation plan to spend $100 million each over the next four years to advance safe, effective, and durable “gene-based cures” for SCD and HIV into clinical trials in the United States and countries in sub-Saharan Africa within the next seven to 10 years.

“We aim to go big or go home,” NIH director Francis S. Collins, MD, PhD, declared Wednesday in a statement. “This unprecedented collaboration focuses from the get-go on access, scalability, and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries.”

The NIH and Gates Foundation said they agreed to co-fund preclinical and clinical studies of potential curative candidates for SCD and HIV, once they are identified. The partners also agreed to define long-term opportunities to work together and with African partners on advancing promising candidates to late-phase clinical trials, with funding to be determined as candidates advance through those studies.

Candidates will be designed to deliver in vivo treatments to the right places in the body, and optimized to target the cells involved in the respective diseases efficiently and specifically, according to the agency and Foundation.

In SCD, they said, the goal is to develop an easy-to-administer, gene-based treatment designed to either correct the SCD gene mutations or promote fetal hemoglobin gene expression to achieve normal hemoglobin function. The treatment will rely in part on the development of gene-based delivery systems capable of selectively targeting hematopoietic stem cells. This will result in the precise correction of gene mutations or addition of a gene to promote sufficient levels of normal hemoglobin expression and function, the NIH and Gates Foundation said.

Multiple approaches

For HIV—with which nearly 38 million people live worldwide—a number of approaches will be considered, with both the Gates Foundation and the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) already funding research designed to develop gene-based treatments in combination with long-acting therapeutics, monoclonal antibodies, and other immune-based targets.

The NIH and Gates Foundation said that their new collaboration will enable them to intensify and better coordinate ongoing research efforts on these strategies, accelerating studies into early phase clinical trials to safely test promising tools and interventions. A particularly appealing approach, they said, entails identifying the location of the reservoir of proviral DNA that lurks within infected cells that still harbor integrated HIV genomes, even after years of effective antiviral treatment, and targeting those DNA sequences with gene editing technology.

The ultimate goal, the NIH and Gates Foundation said, is to scale up and offer these treatments in regions where the diseases have afflicted the most people. Those areas include Africa, where SCD and HIV affect a disproportionate number of people, as the partners noted:

  • Nearly all (95%) of the 38 million people living with HIV globally are in the developing world, with 67% in sub-Saharan Africa, half of whom are living untreated.
  • Fifteen million babies will be born with SCD globally over the next 30 years, with about 75% of those births occurring in sub-Saharan Africa.
  • An estimated 50–90% of infants born with SCD in low-income countries will die before their fifth birthday and SCD is identified as the underlying cause of about 1 in 12 newborn deaths in sub-Saharan Africa.

Harnessing science

“A person’s health should not be limited by their geographic location, whether rural America or sub-Saharan Africa; harnessing the power of science is needed to transcend borders to improve health for all,” stated Gary H. Gibbons, MD, director of the NIH’s National Heart, Lung, and Blood Institute (NHLBI). “Our excitement around this partnership rests not only in its ability to leverage the expertise in two organizations to reduce childhood mortality rates in low-resource countries, but to bring curative therapies for sickle cell disease and HIV to communities that have been severely burdened by these diseases for generations.”

Earlier this month, NHLBI researchers published a study in Nature Communications detailing an effort to develop gene therapies for SCD by creating a viral vector that leaves intron 2 intact but also incorporates a new forward-oriented β-globin vector.

The NIH and Gates Foundation also said that they will continue to invest in other parallel research efforts on cures for SCD and HIV outside of their $200 million collaboration.

For example, NHLBI has already begun to establish a clinical research infrastructure in sub-Saharan Africa. However, according to the Institute, additional clinical research and capacity-building efforts are needed to deliver point-of-care screening, such as at the time of infant vaccinations, and to establish a standard of care. These activities will be undertaken by NIH and Gates Foundation outside of the collaboration, but will support collaboration efforts.

“In recent years, gene-based treatments have been groundbreaking for rare genetic disorders and infectious diseases. While these treatments are exciting, people in low- and middle-income countries do not have access to these breakthroughs,” added Trevor Mundel, MD, PhD, president, Global Health Program, Bill & Melinda Gates Foundation. “By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene-based treatments to the world of public health.”

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