The Philanthropy That Jump-Started a Cure for Sickle Cell Disease

More than a century after sickle cell disease was first diagnosed, the inherited blood disorder appears to be on the verge of a cure. That progress was kick-started, in part, by the Doris Duke Charitable Foundation, which since 2008 has awarded about $35 million to research scientists.

Sickle cell disease has never received much government or philanthropic attention — which is why the Doris Duke Foundation has pushed forward more than 40 research projects over the past 15 years. Past grantees are now overseeing multimillion-dollar, government-funded clinical trials using gene editing to correct the sickle cell mutation and shaping a gene therapy currently under review by the Food and Drug Administration.

“The people [who received Doris Duke grants] have become very, very successful in the field of sickle cell, mentoring other people doing groundbreaking new things or new treatments or showing new ways to prevent sickle cell problems,” says Lewis Hsu, chief medical officer of the Sickle Cell Disease Association of America, which has not received funding from the foundation.

About 100,000 people in the United States — most of whom are Black — suffer from the painful and often fatal effects of sickle cell disease. The Centers for Disease Control and Prevention estimates that one in every 365 Black babies is born with the condition. Yet research funding pales in comparison with cystic fibrosis, another genetic condition that affects 30,000 Americans. Per person, foundations have spent about 75 times more on research for cystic fibrosis than for sickle cell disease, according to a 2020 study.

Currently, the FDA is evaluating two sickle cell gene therapies developed by bluebird bio and CRISPR Therapeutics with Vertex Pharmaceuticals. However, these treatments will likely not be affordable for most patients because the price tag is astronomical and many patients don’t have access to primary or specialty care or may avoid treatment because of the racial stigma associated with disease. Philanthropic support for sickle cell disease patients also remains small.

“The donor base for sickle cell disease is basically Black,” Hsu says. “And I think that that’s where the gigantic, enormous disparity comes [from].”

From Grants to Clinical Trials

Before she died in 1993, the tobacco heiress Doris Duke said she wanted her philanthropy to conduct research to fight sickle cell disease, but she did not say why.

Sindy Escobar Alvarez, who oversees the foundation’s medical research giving, says that chronic lack of funds for sickle cell disease prompted her organization to increase and then provide sustained support starting in 2008.

“We wrestled with how much impact can you have with a small amount of funds,” she says. “As we all know, developing treatments and the whole pipeline from discovery to a treatment takes a long time and also a lot of resources.”

From 2008 to 2015, the foundation gave $17 million to scientists applying techniques from cancer research and other fields to better understand and develop new treatments for sickle cell disease. After researchers in 2012 used a technology called CRISPR to edit genes by precisely cutting DNA and then letting natural DNA-repair processes take over, the foundation shifted focus. Since 2017, Doris Duke has given an additional $17.9 million to scientists exploring gene therapies and drugs for possible sickle cell disease cures.

Gene editing has proved promising because it enables scientists to directly counteract the effects of the sickle cell mutation, which causes hemoglobin to stick together, creating red blood cells with a crescent, or sickle-like, shape. Those misshapen cells create blockages in blood vessels that cause the painful effects of the disease. The only existing cure for sickle cell disease involves a bone-marrow transplant, but finding a matching donor for bone marrow is difficult. Gene editing ensures the cells patients receive are an exact match.

Donald Kohn, a stem-cell researcher at the University of California at Los Angeles, who received three grants from 2010 to 2016 — amounting to about $150,000 a year — is one of the scientists exploring gene-editing technology like CRISPR. He is now part of three separate clinical trials using gene therapy on sickle cell patients to prevent red blood cells from becoming misshapen.

“The basic technology came out of our Doris Duke funding,” he says.

Those philanthropic dollars were especially helpful when he began his research, Kohn says, given that the National Institutes of Health provided limited funds for sickle cell disease in the early 2010s. The Doris Duke grants helped kick-start his project, which has developed into government-funded clinical trials that cost millions of dollars.

Ann Johansson, UCLA Broad Stem Cell Research Center

The Doris Duke Foundation also funded Stuart Orkin, who identified a gene that could be used to create healthy red blood cells in people with sickle cell disease. Orkin and his team found that the gene could be manipulated to produce a type of hemoglobin that isn’t affected by the mutation.

In 2013, the foundation awarded a grant to Orkin and Daniel Bauer of Boston Children’s Hospital for research building off that work. Eventually, they were able to identify the part of DNA that could be used to produce that type of hemoglobin. Vertex Pharmaceuticals and CRISPR Therapeutics are deploying that underlying approach in their gene-therapy cure for sickle cell disease, which may be approved by the FDA as soon as December.

The Doris Duke Foundation awarded additional grants in 2019 to the scientists — to Orkin for research of a drug to produce hemoglobin that doesn’t cause sickle-shaped cells and to Bauer to study aspects of gene editing in sickle cell disease. In total, the foundation awarded $2.8 million in funding to Orkin and $3 million to Bauer for their research.

Another successful Doris Duke grantee is Punam Malik, a Cincinnati Children’s Hospital Medical Center director, who created a sickle cell gene-therapy approach that was licensed to Aruvant Sciences, though the pharmaceutical company discontinued the collaboration over concerns about cost and competition.

Access Challenges Ahead

With the National Institutes of Health and pharmaceutical companies backing clinical trials for sickle cell disease cures, the Doris Duke Charitable Foundation is looking to see where it can make a difference next.

Genetic-therapy affordability is one area. The drug-pricing watchdog Institute for Clinical and Economic Review estimated the gene therapies from bluebird bio and Vertex Pharmaceuticals/CRISPR Therapeutics could cost between $1.4 million and $2.1 million per course of treatment.

“How do we leverage what we have achieved? We think that’s through either advocacy or through these questions” of accessibility, Doris Duke’s Escobar Alvarez says.

In 2022, the foundation awarded $100,000 to the Innovative Genomics Institute to research how to make sickle cell gene therapy more affordable. The institute released a report in July that recommended creating nontraditional pharmaceutical organizations to focus on affordable gene therapies with early-stage funding from philanthropies.

Melinda Kliegman, a director at the institute, notes that while philanthropy is vital in getting new organizations off the ground, it can’t solve the affordability challenge alone.

“The role of philanthropy is really important in making something like this possible,” she says. “But at the same time, it’s just so much money.”

Hsu of the Sickle Cell Disease Association of America says that the uptick in government and pharmaceutical funding hasn’t prompted an increase in philanthropic support. While the Cystic Fibrosis Foundation has an annual budget of more than $400 million and the ability to dole out research grants, the Sickle Cell Disease Association of America’s annual budget is only $3.5 million.

Ashley Valentine, president of Sick Cells, an advocacy organization for people with sickle cell disease, says patient-focused organizations like hers struggle to get grants. Valentine says it’s important for patients’ perspectives to be heard because their experiences are often not reflected in treatment discussions.

“The other piece is the historical racism with sickle cell,” she says. “It takes a trained community member, someone who’s lived this type of experience, to be able to translate what that means in terms of treatment and access and research.”

Escobar Alvarez says that lack of philanthropic support for sickle cell disease has been frustrating, and she regrets not building more ties to grant makers.

“If I went back 10 years, I’d probably push myself to maybe build those partnerships more intently,” she says. “I do wonder what could have been different.”

Reporting for this article was underwritten by a Lilly Endowment grant to enhance public understanding of philanthropy. The Chronicle is solely responsible for the content. See more about the Chronicle, the grant, how our foundation-supported journalism works, and our gift-acceptance policy.