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At the Forefront of Policy and Public Health
CHORI Scientist Receives 1.2 Million FDA Grant

"We thought it made perfect sense to try to treat the PH by replacing the glutamine that's missing."

Pediatriac Emergency Medicine Physician and CHORI clinical scientist Claudia R. Morris, MD, of CHORI’s Center for Sickle Cell Disease and Thalassemia, has received a highly competitive grant through the federal Food and Drug Administration (FDA) orphan drug program to study the nutritional supplement glutamine for the treatment of pulmonary hypertension (PH) in sickle cell disease and thalassemia over a three-year period.

“Our hope is to use glutamine supplementation to increase nitric oxide production and thus decrease the oxidative stress and hemolysis that can lead to pulmonary hypertension in this particularly vulnerable group of patients,” says Dr. Morris.

Within the last 5 years, PH - high blood pressure in the blood vessels leading from the heart to the lungs - has emerged as one of the major causes of death in patients with sickle cell disease, with a tenfold increased risk of mortality. Currently there are no validated standard therapies for treating PH, although studies are ongoing. Glutamine, however, could hold the key to preventing PH from developing in the first place.

"Glutamine is an amino acid, found naturally in our diet, that is metabolized by the body into many different things," explains Dr. Morris. "It's of particular interest for sickle cell disease and thalassemia because we've determined that in this patient population, the severity of a patient's PH is associated with glutamine depletion. We thought it made perfect sense to try to treat the PH by replacing the glutamine that's missing."

The new $1.2 million dollar FDA grant Dr. Morris received will allow Dr. Morris to explore three different aspects of glutamine supplementation. The first is to assess the ways in which supplementation impacts what Dr. Morris calls arginine bioavailability.

"Arginine is one of the many different metabolites that can be produced from glutamine, and is the body's only substrate for nitric oxide production, which is compromised in patients with sickle cell disease and thalassemia," says Dr. Morris. Like glutamine, it too, is found in extremely low levels in this patient population, and should be increased with the addition of its precursor, glutamine.

Dr. Morris will also be conducting pharmacokinetic studies and collaborating with Jung Suh, PhD and Frans Kuypers, PhD, at CHORI to look at different biomarkers associated with oxidative stress and hemolysis - the abnormal break down of red blood cells - both of which are strongly associated with PH.
"The red blood cell is doing so much more than just carrying oxygen and we're only just beginning to understand this. "
"Red blood cells also transport amino acids throughout the body," adds Dr. Morris. "In this study, we’re specifically looking at how certain amino acids in the red blood cell are impacted by adding glutamine to the diet.

The goal is to determine the metabolic fate of glutamine within plasma and the red blood cell with supplementatin, and hopefully find an effective treatment for PH in patients with sickle cell disease and thalassemia. Dr. Morris will receive assistance from the Pediatric Clinical Research Center (CTSI) to complete this study.
"As a benign nutritional intervention, it's very exciting. We often lose sight that nutritional interventions can be very potent, and we're hoping this is one of them," says Dr. Morris.

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Tuesday, May 17, 2011 8:19 AM

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