A team of Brown University researchers has developed a new computer model that simulates the way red blood cells become misshapen by sickle cell anemia. A computer model, developed by researchers at Brown University, can stimulate the way red blood cells change shape and structure in sickle cell anemia. The study was published in Science Advances and can advance drug development by serving its use in the preclinical evaluation phase of therapeutics.
"There are currently only two drugs approved by the FDA for treating sickle cell disease, and they don't work for everyone," said Lu Lu, a Ph.D. student in the Division of Applied Mathematics at Brown and the study's co-lead author. "We wanted to build a model that considers the entire sickling process and could be used to quickly and inexpensively pre-screen new drug candidates."
What is sickle cell anemia? It is a genetic disorder affecting millions worldwide that results in red blood cells becoming stiff, sticky and sickle-shaped like the crescent moon. The irregularity in their shape caused the red blood cells to get stuck in blood vessels, to causing pain and swelling, and result in strokes along with other complications.
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At the cellular level, sickle cell disease affects the hemoglobin molecule, which binds to oxygen in the blood. When oxygen-deprived, hemoglobin will start to clump inside the cell forming long polymer fibers that push against the cell wall and stiffen the cell structure forcing it out of shape.
The developed model combines and simplifies the previous model systems to produce a single kinetic model of the entire cell sickling process. Utilizing information gleaned from detailed supercomputer models, researchers were able to develop a less complicated version, capturing all the important dynamics of the sickling process, and after all cab be run on a laptop.
"Sometimes a drug can be designed to work on one parameter, but ends up having a different effects on other parameters," says George Karniadakis, a professor of applied mathematics at Brown and senior author of the new research. "The model can tell if those effects are synergistic or whether they may negate each other. So the model can give us an idea of the overall effect of the drug."
In sickle cell disease, long polymer fibers that form inside red blood cells can push the cells out of shape. A computer model developed by Brown University researchers simulates the processes and could help in testing new drugs to treat it. Credit: Brown University via ScienceMag.com
"Clinical drug trials are very expensive and the vast majority of them are unsuccessful," Karniadakis said. "The hope here is that we can do in silico trials to screen potential medications before proceeding to a clinical trial."
Researchers validated their model by reproducing the outcomes of prior experiments in the lab and in people.
Source: Science Daily