NIH and Gates Foundation lay out ambitious plan to bring gene-based treatments for HIV and sickle cell disease to Africa

Two major U.S. biomedical research funders each plan to spend at least $100 million over four years on the development of advanced genetic treatments in a region of the world that often has difficulty providing access to even the simplest drugs: sub-Saharan Africa. The National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation today announced an unusual collaboration to launch clinical trials of genetic treatments for HIV and sickle cell disease in the region over the next decade.

The ambitious objective is to avoid costly and logistically impractical strategies that require stem cell transplantation and to develop simpler and more affordable ways to administer genes or genetically modified drugs that can cure these diseases. "Yes, it's bold," said Francis Collins, Director of the NIH, during a press conference on the project this morning. "But if we don't put our best minds, resources and visions together now, we will not live up to our mandate to bring the best science to those who suffer."

After decades of work and failure, the traditional gene therapy approach of administering DNA into the body to replace a defective gene or stimulate protein production is now reaching the clinic for several diseases, including hereditary blindness, neuromuscular disease and leukemia. Animal studies and some clinical trials have suggested that two diseases prevalent in Africa, HIV and sickle cell disease, can be treated with gene therapies or new genome editing tools such as CRISPR.

But in most cases, the introduction of these therapeutic genes or components of a genome editor involves the removal of stem cells from the body, the addition or modification of genes, and then the re-injection of the cells into the body. It is essentially a stem cell transplant with its own cells, an expensive procedure that is also generally risky because doctors destroy most of a patient's existing stem cells by chemotherapy so that the corrected cells can be grafted and grown. It remains out of reach for most populations in sub-Saharan Africa, where few places have the medical infrastructure to support such intensive interventions.

Yet sub-Saharan Africa is home to about two-thirds of the 20 million people with sickle cell disease and 38 million people living with HIV. The NIH-Gates partnership "is an incredible opportunity to find new therapies and possible cures for two diseases that affect millions of Africans and make them available at affordable prices," said Matshidiso Moeti, who heads the Regional Office for Africa at the World Health Organization.

Anthony Fauci, Director of the NIH National Institute of Allergy and Infectious Diseases, noted that if this collaboration were to succeed, it could also result in significant savings. "If we succeed in finding a cure for HIV, it will be important not only for millions of people living with HIV, but also for hundreds of billions of dollars in health care savings," said Mr. Fauci, whose institute is already funding a major HIV treatment initiative.

In sickle cell disease, which involves a defect in the oxygenated hemoglobin of red blood cells, several ongoing clinical trials of gene therapy and genetic modification in the United States and Europe add a new hemoglobin gene to the cells or activate the gene for a fetal form of the protein. Other HIV clinical trials have used CRISPR or other stem cell genome editors to paralyze a receptor, CCR5, on which the virus depends to establish infection.

Instead of modifying a person's stem cells and transplanting them, the new collaboration will seek to transport a therapeutic gene or gene editing tools directly into the body (in vivo) with "vectors" such as viruses or harmless nanoparticles, according to Collins. The treatment itself would be similar to a simple blood transfusion. Although studies are already underway with viral vectors that deliver new genes to certain human tissues, in vivo gene therapy has only been used to modify blood stem cells in animal models of certain diseases. Finding ways to host and modify these cells in people "is a big part" of the collaboration plan, Collins said.

Hematologist Alexis Thompson, of Northwestern University's Feinberg School of Medicine in Chicago, Illinois, who is involved in gene therapy trials for sickle cell disease, describes the NIH-Gates collaboration as "phenomenal". But, she said, it is more urgent to step up efforts to detect sickle cell disease in newborns in Africa and treat them with antibiotics; currently, the majority of them die before the age of 5 from bacterial infections because sickle cell disease prevents the spleen from retaining bacteria and making antibodies. Unless more children with sickle cell disease survive longer, there will be few who can be cured with new genetic treatments," says Thompson. "It's almost like crawling or walking before the sprint." (Gates and the NIH say they intend to support screening efforts outside the new collaboration.)

With regard to HIV, the momentum for the cure is based on two people infected with AIDS who have been cured by stem cell transplants. These two men each had blood cancer that required transplants, which intentionally used blood from donors with white blood cells whose CCR5 receptors were paralyzed. After the transplants, not all of the remaining HIV in these men could enter new host cells, and their infections faded. This new initiative aims to accelerate the development of direct injections of gene publisher components that can target the CCR5 gene in blood cells and maim it. "The potential beauty of in vivo gene publishing is that it could be given in a single injection, healing everyone in an evolutionary way," says Steven Deeks, a leading researcher on HIV healing at the University of California at San Francisco.

The collaboration will also aim to accelerate the development of more experimental interventions that directly excise HIV genetic material from a patient's cells or allow people to artificially make super potent antibodies against the virus. "It may be science fiction today, but one day it may be a real possibility," says Deeks.