Sickle cell disease has endured so long. There should be better treatments.

Sickle cell disease is old, beyond when it was first identified in Western medicine by a medical intern in 1904.

When Dr. Ernest E. Irons first examined the blood of a dental school student suffering from severe anemia at Chicago Presbyterian Hospital, he was stunned. What he saw in the blood of the 20-year-old from Grenada was shocking: crescent- or sickle-shaped red blood cells.

By 1910, Irons’ supervisor, cardiologist Dr. James B. Herrick, who had taken an interest in what he considered an unusual blood disorder, wrote the first medical description of sickle cell disease (SCD), which was published in the Archives of Internal Medicine.

As we observe Sickle Cell Awareness Month, it’s a time to talk about the history of sickle cell disease and draw attention to the treatment options for this painful illness.

While Irons and Herrick studied the first case of SCD in the United States, the sickness dates back hundreds of years. Rare Disease Advisor reports that people from Africa and Mediterranean countries have battled it for generations.

It first appeared in medical documents in Africa in the 1870s and was referred to as “ogbanjes.” The word, according to Rare Disease Advisor, means “children who come and go,” referring to the high number of babies who died of SCD.

The publication also reports a family in Ghana tracked SCD, an inherited blood disorder, back to 1670. The disease, and the genetic mutation that causes it, is much older, dating back thousands of years, researchers suspect.

It took decades to for the government to approve medications

Tabatha McGee

But fast forward to the 20th century again when, in 1949, researchers identified SCD as the first molecular disease of thousands that are caused by dysfunctional proteins when they discovered a specific change in hemoglobin caused it.

Scientists made other discoveries about SCD as the decades passed, and yet 122 years after Dr. Irons first identified sickled red blood cells, treatment options are woefully lacking.

There are several gene therapies billed as cures for SCD, such as Casgevy and Lyfgenia, which were approved in 2023. They do offer transformative approaches, but they’re complex, extraordinarily expensive and almost inaccessible.

For most patients, their main options are managing pain, preventing complications and trying to keep red blood cells functioning normally.

The gap between actual successful SCD treatments beyond the gene therapy cures and when the disease was first identified should make us uncomfortable.

For example, the Food and Drug Administration did not approve hydroxyurea, the first drug for SCD, until 1998, almost 95 years after Dr. Irons first saw sickled cells under a microscope.

For almost two decades, it was the only FDA-approved disease-modifying therapy that helps patients. It can prevent red blood cells from sickling and blocking blood vessels, which can lead to pain crises, hospitalization and worse.

Then, in 2017, L-glutamine, an oral amino acid powder, arrived, followed by crizanlizumab, a monthly intravenous (IV) monoclonal antibody. Both these treatments help protect red blood cells and prevent them from sickling.

But fast forward to the 20th century again when, in 1949, researchers identified SCD as the first molecular disease of thousands that are caused by dysfunctional proteins when they discovered a specific change in hemoglobin caused it.

Scientists made other discoveries about SCD as the decades passed, and yet 122 years after Dr. Irons first identified sickled red blood cells, treatment options are woefully lacking.

There are several gene therapies billed as cures for SCD, such as Casgevy and Lyfgenia, which were approved in 2023. They do offer transformative approaches, but they’re complex, extraordinarily expensive and almost inaccessible.

For most patients, their main options are managing pain, preventing complications and trying to keep red blood cells functioning normally.

The gap between actual successful SCD treatments beyond the gene therapy cures and when the disease was first identified should make us uncomfortable.

For example, the Food and Drug Administration did not approve hydroxyurea, the first drug for SCD, until 1998, almost 95 years after Dr. Irons first saw sickled cells under a microscope.

For almost two decades, it was the only FDA-approved disease-modifying therapy that helps patients. It can prevent red blood cells from sickling and blocking blood vessels, which can lead to pain crises, hospitalization and worse.

Then, in 2017, L-glutamine, an oral amino acid powder, arrived, followed by crizanlizumab, a monthly intravenous (IV) monoclonal antibody. Both these treatments help protect red blood cells and prevent them from sickling.

In 2019, the FDA approved a game-changing treatment: voxelotor, commercially known as Oxbryta.

For patients and doctors, voxelotor represented more than just another prescription. It was a drug designed around the biology of sickle cell disease, increasing oxygen levels in hemoglobin and reducing the sickling and clumping in red blood cells.

When red blood cells begin changing shape and clumping, they have a harder time passing through organs. That can lead to what’s known as pain crises, which often result in hospitalizations, lost time at work and tremendous out-of-pocket medical expenses.

Progress requires having safe, effective, accessible choices

For the sickle cell community, Oxbryta offered real hope, but it didn’t last.

Ongoing studies began raising serious safety concerns. In 2024, the drug’s maker, Pfizer, voluntarily withdrew Oxbryta from the market, and the FDA decided the evidence showed the benefits no longer outweighed the risks.

It’s an example of how desperately SCD needs better treatments. Patients deserve better, and they deserve a medical research system that has not left a devastating inherited disease with so few options for so long.

Sickle cell disease has never been a mystery. We’ve known its cause, its consequences and its molecular basis for generations.

What’s been missing, though, is urgency.

For people living with sickle cell disease, “progress” cannot simply mean that a handful of new therapies finally exist. Progress means having enough safe, effective and accessible choices that losing one drug does not feel like losing hope.

After more than a century, patients are still waiting for the treatment pipeline to catch up with the disease, and it shouldn’t be that way.