CRISPR gene-editing clinical trial at UCSF aims to cure deadly blood disease

New funding to UCSF and S.F. General Hospital provides hope for Bay Area sickle cell patients

By Nick Fouriezos

Special to The Examiner

Brooklyn Haynes had few complaints about the care she received as a child. Since she was two months old, the Alameda County native had been treated by doctors at Oakland Children’s Hospital who specialize in sickle cell, a rare blood disease that affects more than 100,000 Americans, most of whom are Black.

Her care changed as soon as she turned 18. A former Apple technician with a knack for computers and gadgetry, Haynes has had a very different experience seeking treatment as an adult — with emergency room providers often subjecting her to a litany of questions trying to assess if her pain is “real,” despite the fact that her medical records clearly demonstrate her need.

“The pain, it feels like you got shot in one area, then that area is being sawed off and a hammer is hitting it over and over again,” Haynes, now 27, said. “When I transitioned into the adult world, people didn’t believe my pain was real — I was treated like a drug seeker.”

Her experience is far from unusual for people with sickle cell, experts say, due to medical bias and a lack of providers with knowledge of the historically understudied disease. But a slew of recent Bay Area investments in sickle cell research and treatment are providing new hope for them, at a time when their medical concerns are rising due to the COVID-19 pandemic.

In December, UCSF Benioff Children’s Hospital Oakland announced a $17 million research clinical trial grant, the largest in its history, to cure sickle cell using CRISPR gene-editing technology originally developed at UC Berkeley. The hospital also announced a $2 million anonymous gift to support research, education and clinical care. Meanwhile, both UCSF Benioff Children’s Hospital and Zuckerberg San Francisco General Hospital have received a portion of nearly $15 million in state funds approved in 2019 to expand access to sickle cell disease centers across California.

People with the inherited blood disorder have a mix of healthy red blood cells and malformed sickle-shaped red blood cells, which can get stuck in small blood vessels, creating painful blockages. In the $17 million clinical trial, UCSF Benioff doctors will use CRISPR gene-editing technology to modify the stem cells of six adult patients — a transformative process researchers believe could be a blueprint for curing other ailments as well.

Dr. Mark Walters, UCSF pediatric hematologist-oncologist, is the principal investigator of a $17 million clinical trial that will use CRISPR gene-editing technology to modify the stem cells of six adult patients with sickle cell disease. (Courtesy UCSF)

Dr. Mark Walters, UCSF pediatric hematologist-oncologist, is the principal investigator of a $17 million clinical trial that will use CRISPR gene-editing technology to modify the stem cells of six adult patients with sickle cell disease. (Courtesy UCSF)

“If we can get this to work in sickle cell, then there are hundreds of thousands of other patients with other blood diseases and hemoglobin disorders that we could theoretically tackle,” said UCSF Benioff Pediatrics Professor Mark Walters, the principal investigator of the clinical trial and gene editing project.

The $15 million in state funding will be critical for Bay Area hospitals seeking to better treat sickle cell patients — particularly for Zuckerberg San Francisco General Hospital, which has had few specialized resources to offer those with sickle cell. The hospital is using the money to add three positions in 2022: a new physician, a full-time sickle cell program coordinator/patient advocate and a part-time social worker dedicated to helping those with sickle cell access benefits and community resources. Until now, San Francisco General has had only two staff members for hundreds of sickle cell patients: a hematologist, Peter Sayre, and a physician assistant, Robin McBride.

The 20-bed Sickle Cell Anemia Center at UCSF Benioff Children’s Hospital Oakland, which is open to both adults and children, is equipped to deliver intravenous pain medication to patients. That type of relief isn’t possible at San Francisco General’s clinic, which is open only two-and-a-half hours a week, has no dedicated beds for inpatient treatment and currently can prescribe only oral painkillers that research has shown is less effective.

“It doesn’t feel particularly accessible to patients,” said Sayre, who has worked at San Francisco General for three years. “Having the additional people will help us work with the clinic, and try to get some more dedicated space for those with sickle cell, some more nurses and, in general, a better process within the hospital system.”

Care that inaccessible has led many with sickle cell to seek treatment through the emergency room. There, advocates and patients say they wait for hours, often lumped in with people experiencing homelessness, and are sometimes accused by providers unfamiliar with sickle cell disease of seeking opioids to get high.

“In my own institution, outside of hematology groups, doctors won’t even prescribe narcotics. They’re afraid to put their names on it; they are facing such scrutiny from the state,” said sickle cell expert Elliott Vichinsky, director of hematology and oncology at UCSF Benioff.

One in 365 Black Americans exhibit the disease, according to the Centers for Disease Control. Hispanics are also at heightened risk, at 1 in 16,300. American researchers have also seen a rise in sickle cell cases among those with South Asian and Mediterranean backgrounds.

Regardless of race, significant disparities exist between pediatric and adult care. Vichinsky and other researchers have found that having access to adult comprehensive services can mean a two-decade difference in average lifespan. “That difference in survival is related to the lack of standard care,” Vichinsky said.

During the COVID pandemic, providers have had to personalize their approach to encourage vaccinations for those with sickle cell. Ylon Hunt, a 39-year-old clinical specialist with sickle cell, first watched her colleagues safely take the vaccine and then followed suit and encouraged others. “It’s a sensitive issue and there are some trust issues,” Hunt said.

Growing awareness of the disease could reduce bias from providers, particularly if California’s plan to expand sickle cell centers across the state is successful. And a cure for sickle cell, like the one being tested in the UCSF Benioff clinical trial, would make opioids less necessary in treating those born with sickle cell — especially if doctors can use CRISPR technology to alter genes in early childhood.

Researchers are hopeful that a cost-effective cure for sickle cell is on the horizon, thanks in part to the Bay Area’s major contributions to the field. Bertram Lubin, the former UCSF Benioff CEO and president, was a trailblazer in studying sickle cell and leading National Institutes of Health studies of the rare blood disease. UC Berkeley scientist Jennifer Doudna is a co-winner of the 2020 Nobel Prize in chemistry for developing CRISPR.

Researchers at the Sarah Cannon Research Institute in Nashville, Tenn., are already testing one possible cure for sickle cell disease. Their approach focuses on raising fetal hemoglobin levels, which are considered an antidote to sickle cell, rather than directly replacing problematic cells, Walters said: “I prefer our approach because it permanently eliminates the mutation from the blood stem cells. We’re directly fixing the problem.”

Walters continued: “As these tools are used more, and as more of the manufacturing procedures become automated, the cost of making the cells should come down as well, which could create a whole pipeline of new options that patients can choose from to make up for past lost ground.”

Haynes is cautiously optimistic about these possibilities, given her past experiences while seeking treatment. Yet she would like to be included in the trial, so that she could work in tech again or become a nurse one day. “I want to get my hopes up and be excited about it,” she said.

This article was funded in part through a reporting grant from Sick Cells, a national sickle cell advocacy nonprofit, as part of its “Project SCoviD” initiative. The grant did not include prior approval of the article.

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