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Georgia Regents University gets big grant to battle sickle cell disease

Sunday, Sept. 22, 2013 6:29 PM
Last updated Tuesday, Oct. 8, 2013 2:58 PM
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You don’t have to tell Ash­ley Williams that her sickle cell disease can lead to lung damage. She’s felt it.

Georgia Regents University nurse Regina Canty searches for a vein to start an IV on sickle cell patient Ashley Williams.   TOM CORWIN/STAFF
TOM CORWIN/STAFF
Georgia Regents University nurse Regina Canty searches for a vein to start an IV on sickle cell patient Ashley Williams.

“It’s hard to breathe, your chest hurts, your lungs hurt,” said Williams, 28. “Really, your whole body hurts.”

Exactly how the disease causes damage in the lungs and kidneys and creates pain crises is the subject of an $8.8 million, five-year grant to researchers at Georgia Regents and Rutgers universities.

They are zeroing in on a particular receptor for the endothelin protein, long known to be a powerful constrictor of blood vessels. One GRU team already has a large grant to study the effects this endothelin A receptor has in the kidney in a diabetes model.

“We think the same thing is happening in sickle cell,” said Dr. David Pol­lock, a regents professor of medicine at GRU and a project leader on both grants. “We have preliminary evidence to suggest such things.”

In the small blood vessels of the kidney, where waste is filtered out, the blood pressure is already higher than in other small blood vessels in the body, he said.

“They are more susceptible to injury when things go wrong,” he said.

In the lungs, higher endothelin A activity could be leading to inflammation that leads to an exaggerated response that can spiral out of control, said Dr. Steffen E. Meiler, a professor of anesthesiology and perioperative medicine at GRU and a project leader on the new grant.

“It just begins to create a vicious cycle that can easily end up in death in these patients,” he said.

A collaborator at Rutgers has preliminary evidence that the protein could be involved in pain hypersensitivity
in sickle cell disease, Pollock said. Pain crises are a common and debilitating complication of sickle cell disease.

Being able to draw on expertise already at GRU and approach the issue from different angles is an important part of the grant, Pollock said.

“This is a big center grant, and the idea is that each of us bring special expertise that’s relevant to the potential use of endothelin (inhibitors) in sickle cell disease,” he said.

Those inhibitors are already being tested in clinical trials to see whether they can prevent diabetes-related kidney damage, Pollock said.

The GRU grant will test them in animal models of sickle cell disease first and then hopefully soon after in clinical trials as evidence for their use warrants, said Dr. Abdullah Kutlar, the director of the GRU Comprehensive Sickle Cell Center.

There are relatively few effective therapies for sickle cell patients, he said.

Williams, who is already participating in one clinical trial of a potential new drug for sickle cell, said she makes it a point to do so when she can. The need for better therapies is obvious to her.

“Especially when it just hurts to breathe,” Williams said.


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