Source: sciencemag.org<\/p>\n
Two major U.S. biomedical research funders plan to each put at least $100 million over 4 years toward bringing cutting-edge, gene-based treatments to a part of the world that often struggles to provide access to even basic medicines: sub-Saharan Africa. The National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation today\u00a0announced\u00a0the unusual collaboration to launch clinical trials for gene-based cures for HIV and sickle cell disease within the region in the coming decade.<\/p>\n
The ambitious goal is to steer clear of expensive, logistically impractical strategies that require stem cell transplantation, and instead develop simpler, affordable ways of delivering genes or gene-editing drugs that can cure these diseases. \u201cYes, this is audacious,\u201d NIH Director Francis Collins said during a press teleconference this morning on the project. \u201cBut if we don\u2019t put our best minds, resources, and visions together right now, we would not live up to our mandate to bring the best science to those who are suffering.\u201d<\/p>\n
After decades of work and setbacks, the traditional gene therapy approach of delivering DNA into the body to replace a defective gene or boost a protein\u2019s production is now reaching the clinic for several diseases, including inherited 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 by gene therapies or newer genome-editing tools such as CRISPR.<\/p>\n
But in most cases, introducing those therapeutic genes or the components of a genome editor involves removing stem cells from the body, adding or modifying genes, then reinfusing the cells back into the body. That is essentially a stem cell transplant with one\u2019s own cells, an expensive procedure that is also typically risky because physicians wipe out a patient\u2019s existing stem cells with chemotherapy so the corrected cells can engraft and grow. It remains out of reach for most people in sub-Saharan Africa, where few places have the medical infrastructure to support such intensive interventions.<\/p>\n
Yet sub-Saharan Africa is home to about two-thirds of the 20 million people with sickle cell disease and the 38 million living with HIV. The NIH-Gates partnership \u201cis an incredible opportunity to find new therapies and possible cures for two diseases that affect millions of Africans and to make them available at affordable costs,\u201d said Matshidiso Moeti, who heads the Regional Office for Africa at the World Health Organization.<\/p>\n
Anthony Fauci, director of NIH\u2019s National Institute of Allergy and Infectious Diseases, noted that if this collaboration pans out, it could also lead to enormous cost savings. \u201cIf we do successfully achieve an HIV cure, it will ultimately be important not only for millions of individuals with HIV, but also will save hundreds of billions of dollars in health care costs,\u201d said Fauci, whose institute already funds a major HIV cure initiative.<\/p>\n
In sickle cell disease, which involves a defect in the oxygen-carrying hemoglobin in red blood cells, several ongoing gene therapy and gene-editing clinical trials in the United States and Europe are either adding a new hemoglobin gene to cells or turning on the gene for a fetal form of the protein. Other clinical trials for HIV have used CRISPR or other genome editors in stem cells to cripple a receptor, CCR5, that the virus depends on to establish infection.<\/p>\n
Instead of modifying a person\u2019s stem cells and transplanting them back, the new collaboration will seek to ferry a therapeutic gene or gene-editing tools directly into the body (in vivo) with \u201cvectors\u201d\u00a0such as harmless viruses or nanoparticles, Collins said. 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 tissues in people, in vivo gene therapy has only been used to modify blood stem cells in animal models of certain diseases. Figuring out how to home in on and modify those cells in people \u201cis a big part\u201d of the collaboration\u2019s plan, Collins said.<\/p>\n
Hematologist Alexis Thompson of the Northwestern University Feinberg School of Medicine in Chicago, Illinois, who is involved with some sickle cell gene therapy trials, calls the NIH-Gates collaboration \u201cphenomenal.\u201d\u00a0But, she says, a more urgent need is to expand efforts to screen newborns in Africa for sickle cell disease and treat them with antibiotics; at the moment, the majority die before age 5 from bacterial infections because the sickled cells impair the spleen\u2019s ability to filter bacteria and make antibodies. Unless more children with sickle cell disease mutations survive longer, there will be few to be cured with the new gene-based treatments, Thompson says. \u201cIt\u2019s almost being able to crawl or walk before you sprint.\u201d\u00a0(Gates and NIH say they plan to support screening efforts outside of the new collaboration.)<\/p>\n
For HIV, a big impetus for the cure push builds on two people infected with the AIDS virus who were cured with stem cell transplants. These two men each had blood cancers that required the transplants, which intentionally used blood from donors who had white blood cells with crippled CCR5 receptors. After the transplants, whatever HIV remained in these men could not enter new host cells, and their infections petered out. This new initiative hopes to speed development of direct injections of gene editor components that can target the\u00a0CCR5<\/em>\u00a0gene in blood cells and cripple it. \u201cThe potential beauty of in vivo gene editing is that it might be given ultimately as a single shot, curing everyone in a scalable manner,\u201d says Steven Deeks, a leading HIV cure researcher at the University of California, San Francisco.<\/p>\n The collaboration will also try to speed development of more experimental interventions that directly excise HIV\u2019s genetic material from a patient\u2019s cells or allow people to artificially make superpotent antibodies against the virus. \u201cThis might be science fiction now, but one day may be a real possibility,\u201d Deeks says.<\/p>\n\n\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":2412,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5],"tags":[2198,2196,52,2197,584],"class_list":["post-2411","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-aids-hiv","tag-africa","tag-gates-foundation","tag-hiv","tag-sickle-cell","tag-treatments"],"yoast_head":"\n