1 min readPotential Treatment for Sickle Cell Disease Found
Ann Arbor, MI – A University of Michigan Health System laboratory study reveals a key trigger for producing normal red blood cells that could lead to a new treatment for those with sickle cell disease.
The study, conducted in mice, holds promise for preventing the painful episodes and organ damage that are common complications of sickle cell disease.
According to the U-M study, increasing the expression of the proteins, TR2 and TR4, more than doubled the level of foetal haemoglobin produced in sickle cell mice and reduced organ damage.
It’s the first time specific proteins have been targeted to prevent a disease, authors say.
The study appears in this week’s early edition of the Proceedings of the National Academy of Sciences.
“The vast majority of sickle cell disease patients are diagnosed early in childhood when adult haemoglobin normally replaces foetal haemoglobin, but the severity of the disease can differ markedly, correlating most strongly with the level of foetal haemoglobin present in red cells,” says paediatrician and lead study author Dr. Andrew D. Campbell, director of the Pediatric Comprehensive Sickle Cell Program at the U-M Cancer Center.
Sickle cell is an inherited blood disorder impacting hundreds of thousands of patients worldwide that causes normal red blood cells to change shape to a crescent moon.
The result is life-long debilitating pain episodes, chronic organ damage and significantly shortened life span. But a small number of sickle cell patients are born with a high enough foetal haemoglobin level to moderate these complications.
The study team, that included paediatric haematologists, cell and developmental biologists and pathology experts at U-M and the University of Tsukuba, Japan, demonstrated a potential method for boosting the foetal haemoglobin levels by modulating TR2/TR4 expression.
“While the average foetal haemoglobin was 7.6 percent in the sickle cell mice, the TR2/TR4 treated sickle cell mice had an average foetal haemoglobin of 18.6 percent,” says senior study author Dr. James Douglas Engel, professor and chair of the U-M’s Cell and Development Biology Department.
He adds that anaemia and red blood cell turnover all improved within the TR2/TR4 mice. Additional studies, including clinical trials, would be required to determine if the technique could help humans.
“Currently hydroxyurea is the only FDA approved drug known to increase the levels of foetal haemoglobin within sickle cell disease patients and a substantial number of patients do respond to it,” says Campbell, the paediatric haematology oncology specialist. “But the long term consequences for hydroxyurea are unknown, especially in children.”