A drug already approved to address a form of cancer could play a role in treating sickle cell disease, scientists at the Feinstein Institute for Medical Research in Manhasset have found.
Lionel Blanc, an assistant investigator at Feinstein, is leading an investigation into a treatment for sickle cell disease by re-purposing a drug used to combat multiple myeloma, a cancer of a key population of white blood cells. Sickle cell disease, while not a cancer, belongs to a group of anemias known as the hemoglobinapathies.
The research is the first worldwide to highlight how a drug known as pomalidomide, a derivative of thalidomide, increases the production of healthy hemoglobin — the crimson-colored protein that ferries oxygen to the body’s tissues.
In early laboratory studies, Blanc said pomalidomide prevents the deadly sickling of red blood cells in people with the disease. Thalidomide, a drug prescribed to treat morning sickness in the early 1960s, caused severe birth defects. Children of these mothers were born with malformed limbs.
But pomalidomide has been used for more than 15 years in the fight against recurrent multiple myeloma, a cancer of the body’s B cells, also called plasma cells, which begin their formation in the bone marrow as do all blood cells.
Blanc said pomalidomide, at least in the laboratory, helps produce “fetal hemoglobin,” a form of the protein that can effectively transport oxygen.
“There are still pieces of the puzzle that need to be completed,” said Blanc, who is collaborating with medical investigators at the New York Blood Center in Manhattan and scientists at the University of Montpellier in France. At the Feinstein, a division of the North Shore-Long Island Jewish Health System, Blanc is member of the Laboratory of Developmental Erythropoiesis.
Blanc said pomalidomide has a completely different mechanism of action in multiple myeloma compared with what he and his colleagues have seen so far in the lab with sickle cell disease.
“In multiple myeloma, pomalidomide kills the cancer cells, but in sickle cell disease it does not,” he said.
He plans a clinical trial of the medication probably by mid-2016.
Blanc said his preliminary research shows pomalidomide more robustly spurs the production of healthy hemoglobin compared with hydroxyurea, the only approved medication for sickle cell disease. Hydroxyurea works well only in some patients, according to patient advocates, leaving many people without an effective medication.
Sickle cell disease is a devastating blood disorder largely affecting African-Americans and people of Caribbean and African heritage in the United States. The disorder derives its name from the shape of patients’ red blood cells, which have the configuration of a crescent moon or sickle. The disorder affects about 100,000 people nationwide.
The disorder not only causes an extreme form of anemia — a lack of oxygen transportation to tissues — but excruciating pain when malformed blood cells jam in capillaries and are unable to flow like healthy disc-shaped red cells.
Gloria Rochester, founder and president of the Queens Sickle Cell Advocacy network, said she welcomes new advances for sickle cell disease.
“I am a parent of a 42-year-old daughter who was diagnosed with sickle disease,” Rochester said. “My hope is to see a cure for sickle cell.”
Medical theorists have long posited that sickle cell and similar diseases evolved as nature’s way to combat malaria, a parasitic disease transmitted by mosquitoes. In Africa, some people are impervious to certain malaria parasites, scientists say, because the parasite cannot proliferate in sickled cells. The condition is genetically transmitted.
As one of the hemoglobinapathies, doctors say the disorder is similar to beta thalassemia, which is largely seen in populations throughout the Mediterranean, parts of the Mideast and Asia. In that disease, red blood cells do not sickle but are substantially smaller than normal, making them poor oxygen transporters. Theory holds that beta thalassemia also may have evolved in response to malaria.
Blanc said Thursday that he thinks pomalidomide might also be effective in the treatment of beta thalassemia, but he has yet to test the drug in that disease.