One of these researchers, Versiti Blood Research Institute (VBRI) Senior Investigator Prithu Sundd, PhD, is interested in exploring how two types of cells—neutrophils and platelets—contribute to thrombosis and inflammation (thrombo-inflammation) in SCD. “The science I’ve been doing all my life relates to finding new therapies for sickle cell disease,” he says. “I also aim to understand the current therapies, where there is a gap, and the factors that affect patients’ lifestyles, outcomes and quality of life.”
Investigating lung injury in sickle cell disease
In 2013, Dr. Sundd joined the University of Pittsburgh, where he began conducting basic translational research of SCD in an effort to develop new treatments. He learned that many SCD patients develop acute chest syndrome, a pneumonia-like illness that is a leading cause of hospitalization and death. At the time Dr. Sundd began his research, it was unknown whether the stoppage of blood flow in blood vessels was to blame, but researchers were already beginning to examine how high levels of platelets and leukocytes (a type of immune cell) might play a role.
“I came up with my own understanding that it’s possibly the interaction between the leukocytes and platelets,” Dr. Sundd said. “These two cells crosstalk and interact with red blood cells to cause the stoppage of blood flow.”
For the last 10 years, he has been researching the cause of this pathophysiology, and was one of the first to show that blocking P-selectin, a molecule on platelets and endothelial cells, helped to prevent further lung injury. P-selectin antibody was FDA approved in 2017 as a prophylactic therapy to reduce hospitalization of SCD patients; however, it only gives partial protection, Dr. Sundd said. “Over the last couple of years, we have identified new mechanisms that may fill the gap not covered by P-selectin Ab therapy and thus, may inspire a combination therapy to reduce hospitalization and halt the progression of lung injury in hospitalized SCD patients.”
More recently, he and a team of researchers were published in the prestigious journal Blood for their work showing how neutrophils, the most abundant type of white blood cell in human blood, contribute to lung injury in SCD.
“We are investigating these patients, who have a lot of cell death in their bodies,” Dr. Sundd said. “When cells die, they release their DNA, which circulates in their blood. We are trying to understand how that DNA acts to promote thrombosis, inflammation, acute lung injury and organ injury.”
Development of new therapies
The current treatments provided by hospitals to treat the symptoms of SCD are either supportive or prophylactic. “The only therapies available are maintenance therapies,” Dr. Sundd said. “Patients are given antibiotics, oxygen, fluids and blood transfusions. Although new therapies like P-selectin Ab therapy are very effective, they are still mostly prophylactic. Our goal is to find therapies that can be used as rescue therapies to resolve the pain crisis or halt the development of lung injury in hospitalized SCD patients.”
“And as these new therapies grow, we need to think about chronic organ damage in sickle cell disease, because these patients will live longer with the disease,” he added. “We have to focus on finding therapies to tame the disease, tame the thrombo-inflammation, tame the organ injury, and prevent emergency hospitalizations. That is the focus of our program.”
To accomplish this, Dr. Sundd collaborates with researchers and physicians at Froedtert Hospital and the Medical College of Wisconsin, particularly Froedtert’s Adult Sickle Cell Clinic, run by VBRI adjunct Senior Investigator Joshua Field, MD, MS. In his work, Dr. Field sees patients with myriad SCD complications, including pain crises, organ damage, strokes and spleen problems.
“The future is promising. The time is coming when these patients will come in with a pain crisis and there will be a therapy to resolve it,” Dr. Sundd said. “Hopefully one day, gene therapy will be available to permanently cure the disease. Meanwhile, we need to find therapies that will make patients’ quality of life better and more affordable.”
Why VBRI?
After pursuing a highly prolific research career for more than a decade at the University of Pittsburgh School of Medicine, Dr. Sundd sought a research environment with a focus on blood disorders and hematology. “I was looking for an environment where I can have the resources to make an even stronger impact in the field of SCD,” he said. “Being a large blood center, home to the world-renowned Versiti Blood Research Institute and academically associated with Medical College of Wisconsin, Versiti has the perfect environment and resources to help me take my scientific discoveries to the next level.”
About the expert: Prithu Sundd, PhD, is a senior investigator at Versiti Blood Research Institute.