The results of two first-in-human trials suggest promising initial results for ground-breaking approaches to stem cell transplantation and gene therapy for Sickle Cell Disease.
Individuals with SCD, an inherited blood disease, produce abnormal hemoglobin, a protein in red blood cells that attaches to oxygen in the lungs and carries it to all parts of the body. Red blood cells that contain normal hemoglobin are donut-shaped and flexible so that they can travel smoothly through the smallest blood vessels. In SCD, however, the red blood cells are sickle-shaped and rigid and can get stuck in these vessels, blocking the flow of blood and oxygen to the body and leading to intense pain and other serious issues such as stroke, infection, pulmonary complications, and even death.
For Lynndrick Holmes, 29, of Mobile, Ala., two years of gene therapy as part of a clinical trial for a new sickle cell treatment, appears to have cured him of the condition.
The treatment involves taking stem cells from the patient’s bone marrow and tweaking the gene that causes cells to become misshapen, says Julie Kanter, MD, director of the Adult Sickle Cell Clinic at the University of Alabama at Birmingham, one of the trial sites. The modified gene is then put back in using deactivated HIV. The trial is sponsored by biotech company bluebird bio and has test sites across the country.
Holmes said, ‘“Sickle cell is like a stalker -- you don’t know when he’s watching or what he’s planning. But now I feel amazing. I feel incredible. It’s been painful, socially awkward, and just awful. The trial has totally changed my life.”
The introduction of deactivated HIV into the system raised the ire of laypeople, however, the NIH explained the process involved taking stem cells from his bone marrow, fixing the gene that causes cells to sickle and reinserting that gene using the HIV virus; minus the parts of the virus that cause infection. That last part of the process happens after patients undergo chemotherapy to prepare for the introduction of the new cells.
Kanter, who works as part of a team at the National Institutes of Health said, "We take the HIV envelope and we take out the letter that actually encodes for the bad stuff, the virus, but we leave the envelope that allows it to get into cells. We put in what I call a new letter, a letter that spells the right kind of hemoglobin. So now it’s in an envelope and it delivers it into the stem cells of someone with sickle cell disease. Then it produces that normal hemoglobin.”
The relationship between Black bodies and the medical community has historically warranted suspicion and reserve. Whether situated around unethical practices and lack of informed consent — including cases of coerced sterilizations (Mary Alice Minnie Relf, 1974) and the Tuskegee Serological tests (Tuskegee Experiments, 1932-1972), many members of marginalized communities court a healthy distrust trials and experimental therapies.
“There are reasons to be cautious when choosing to participate in clinical trials. The hope for a cure from a debilitating disease can cause a vulnerable population to take unnecessary risks,” Dr. Sophia Sparks, (pictured above) told ACUMEN. “The gene therapy used to treat Sickle Cell Disease in this study uses viruses to insert new genetic material into cells. The use of viruses in gene therapy has caused infections within patients, so, participants have to factor in what risks they are willing to take. Is it worth swapping one disease for another?”
Sparks said that even when patients know the risks, they may not be aware of the number of individuals in whom the treatment is allowed to fail and still be counted a success.
“The reality is that experimental trials require African American participants for sickle cell. These subjects must be willing to assent the acceptable risks determined by researchers and not themselves. How do we know if the effects are long lasting? Further, we cannot claim a cure after a year post-treatment,” Sparks said.