Researchers present new implications for treating sickle cell disease
Monday, April 22, 2019
In sickle cell disease (SCD), hemoglobin molecules form into fibers that act like stiff rods within the red blood cells. The changing shape from disc-shaped to crescent or sickle shape, contribute to blockages in blood vessels that slow or stop the flow of blood. When oxygen can't reach nearby tissues, patients suffer severe pain as well as the risk of stroke and infections.
Millions of people throughout the world are affected by SCD, especially those in sub-Saharan Africa, South America, the Caribbean, Central America, Saudi Arabia, India, and Mediterranean countries. SCD occurs more often among people from parts of the world where malaria is or was common.
SCD affects approximately 100,000 Americans and occurs in about 1 out of every 365 black births and 1 out of every 16,300 Hispanic births. About 1 in 13 black babies are born with sickle cell trait (SCT).
Recent decreases in SCD mortality in black children under age 4 may be related to the introduction of the 7-valent pneumococcal conjugate vaccine in 2000. The lack of any significant reduction in SCD mortality in older children indicates a need for new treatments.
Although the causes of SCD have been known at the molecular level for decades, the disease has never been studied at the level of detail it recently was by biomedical engineers in the University of Minnesota College of Science and Engineering.
According to David Wood, an associate professor of biomedical engineering at the university, the researchers were surprised at what they discovered at the nanoscale — that the disease self-assembly process is less efficient. This means that developing new medicines that are effective at lower doses and cause fewer side effects might be easier than originally thought.
In this study, researchers performed the highest-ever resolution measurements of single sickle hemoglobin fiber assembly in action using microscopes and cameras that can measure the molecules at the nanoscale. Their measurements show that the rates of sickle hemoglobin addition and loss have been underestimated in previous studies.
The new results reveal that the sickle hemoglobin self-assembly process is very rapid and inefficient. They found that the process is 4 percent efficient versus 96 percent efficient, as researchers previously thought. Wood likens the process to stacking Legos, explaining that for every 100 Legos, only four actually stay on as part of the tower. Another 100 Legos would need to be stacked to get another four to stay on.
In other words, according to Wood, the process of sickle cell formation is much less efficient than previously thought. He claims that it would not take as much medicine to disrupt the process.
Only two FDA-approved medicines are currently available to treat those with SCD. Newer alternatives to existing medications are in development, including stem cell transplants and gene therapy.
The researchers in this study are hoping that the new information revealed in their research could make a big impact in developing medicines and other treatments for the millions worldwide who suffer with this painful disease.
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