Science Might Finally Have a Fix for This Rare Blood Disorder
WHY YOU SHOULD CARE
A potential new treatment could tackle the most common blood disease in the African American community.
By Nick Fouriezos
- Sickle cell disease affects an estimated 100,000 Americans. It can cause intense pain episodes and lead to organ failure.
- Now scientists believe they may have developed a new strategy that could keep the condition in check while also reducing pain.
Ashley Valentine spent so much time at the hospital side of her brother, Marqus, that playroom attendants became a common part of her childhood. Her brother, five years older, was born with sickle cell disease, the most prevalent genetic blood-related condition within the African American community, which affects an estimated 100,000 U.S. citizens. In addition to producing healthy, round red blood cells, patients with this condition have C-shaped “sickle” cells that can block blood flow and deprive organs of oxygen. Pain crises, near-constant fatigue and swelling are common symptoms.
Despite those challenges, Marqus, who unexpectedly passed away in June at 36, was a beacon of hope for the sickle cell community. He studied film, become an avid gamer and was an aspiring graphic novelist. His channel on Discord, the instant messaging platform, became a hub for other sickle cell patients to find community and inspiration. And Marqus’ optimism about a next wave of therapies on the horizon — including one he had started — lives on in Ashley. “We had never seen him react so positively to medicine as he was when he started this new treatment,” says Ashley, who, with Marqus, co-founded an advocacy nonprofit called Sick Cells.
Cell sickling leads to chronic anaemia and vaso-occlusive crises [a complication of sickle cell disease]. By providing a molecule … with the proper horsepower, you could potentially address both.
Dr. Jay Janz, Pfizer rare disease research unit
There are reasons to be hopeful, despite a painstakingly long process to get here. Sickle cell disease was discovered in 1910, yet the first medication to address it, hydroxyurea, wasn’t approved by the Food and Drug Administration until 1998 — and even then only for patients older than 18 with at least three pain crises a year. It was approved for pediatric use in 2017. But while hydroxyurea can reduce the occurrence of pain crises it does so indirectly and does not modify the cause of sickling — sickle hemoglobin, which is different from normal hemoglobin. Patients still needed infusions and relied on painkillers, mostly opioids, to manage episodes of intense, often debilitating pain.
Last November, the FDA approved two new non-opioid drugs that address pain crises. Meanwhile, a study led by Ohio State University, published in July, found that as many as nine molecule candidates were worth exploring for their ability to potentially help treat sickle cell patients. “With further testing and in vivo characterization, these drugs have real potential for combating SCD on a global scale,” the study authors, led by hematologist Matthew Cannon, concluded.
In sickle cell disease, hemoglobin — the abundant, oxygen-carrying protein in red-blood cells — is mutated, and when not oxygenated may form polymers, which leads to cell sickling and disease manifestation. Cutting-edge research has led to the emergence of a potential new oral therapeutic that could ensure that hemoglobin molecules do not form polymers. Inhibiting sickling would reduce cell lysis — where the cell’s outer membrane is broken — and improve anemia, possibly reducing episodes of pain. That could fundamentally change the lifestyles of sickle cell patients.
“Cell sickling leads to chronic anaemia and vaso-occlusive crises [a complication of sickle cell disease],” says Dr. Jay Janz, a project leader within Pfizer’s rare disease research unit. “By providing a molecule that inhibits hemoglobin from forming polymers and inhibits cell sickling with the proper horsepower, you could potentially address both these disease aspects and develop a treatment that would hopefully be transformational to the patients we serve.”
Targeting sickle hemoglobin directly has proved problematic given the large abundance of hemoglobin in the blood that would potentially require modification. Scientists have been concerned about impacting oxygen delivery in the body. But it turns out scientists may only need to achieve 2-25 percent coverage for impactful outcomes. That’s still a large drug dosage that would need to be optimized for, “but we believe it’s achievable,” Janz says.
“Having a medication that really fixes it, that treats the pain crises on a molecular level and addresses the anemia, could be life-changing for patients,” Ashley says.
Of course, medical breakthroughs won’t solve the social and cultural barriers to addressing the disease. Ashley believes it’s no coincidence that a disease that predominantly affects Black Americans has been historically under-researched and undertreated. “It’s an important first step, even acknowledging that racism influences how people administer care,” Ashley says. There needs to be a greater awareness of sickle cell disease societally. In September, Ashley participated in a roundtable at the White House with First Lady Melania Trump to discuss finding a cure and sharing the experiences of patients.
African American sickle cell patients face stigmas that others with chronic pain encounter, although it’s exacerbated by the so-called war on drugs that has created and reinforced racial stereotypes. “Some of the stigma is that sickle cell patients are drug seekers,” Ashley says. A hospital staffer once refused to give Marqus pain relief medication, suggesting he was an addict, despite his doctor prescribing a new dosage earlier that morning.
All these factors are why a well-thought-out, extremely patient and deeply researched approach is critical. Some past clinical trials on experimental treatments for sickle cell disease have failed after years of efforts by scientists. Yet, scientists say, those failures are often crucial steppingstones toward a better understanding of the disease and eventual treatments.
Some research groups are increasingly engaging with the patient community during the drug development process to gain a better understanding of what issues patients face. For example, in addition to pain episodes, chronic fatigue has a major impact on patients’ day-to-day lifestyles. Informed by the patients’ experience, scientist are looking to “take a holistic approach to develop end points that address all of ways the disease impacts a patient’s life,” Janz says.
All of that is providing hope for tens of thousands of people with sickle cell disease. “Overall, we are seeing this as a renaissance moment for the sickle cell community,” Ashley says.