First Human Data Reported on Safety and Viability of Virally Inactivated Red Blood Cells

Lebanon, NH - Dartmouth Medical School pathologist James P. AuBuchon, MD, today, reported results of the first human trial demonstrating that red blood cells virally inactivated with an experimental compound can be stored for 28 days, retaining their viability and subsequently can be safely reinfused into human volunteers. AuBuchon, professor and acting chair of pathology, presented the clinical data at the annual meeting in San Francisco of the American Society of Hematology.

"This research supports a new approach to enhancing the safety of the worldwide transfusion blood supply," noted AuBuchon. "Despite reductions in the risk of pathogen transmission by blood transfusion, there remains a residual risk of disease transmission from known and as-yet undiscovered pathogens. Use of viral inactivating agents represents one potential avenue to reducing this risk. However, viral inactivation presents a number of challenges, notably to preserve red blood cell function."

He added, "In this study we evaluated the impact on red blood cells of a new compound that has shown activity against a wide range of both enveloped and non-enveloped viruses. Our study indicated that after 28 days of storage, treated cells met all the requirements for therapeutically useful red blood cells. Additional studies are ongoing to evaluate red blood cell viability for more extended periods."

The randomized crossover study involved 12 healthy adults. Blood in the test units was treated with 0.1 percent PEN110, a compound that binds to nucleic acids such as viral DNA or RNA. Treated cells were stored at four degrees Celsius for 28 days, followed by a procedure to remove the viral inactivating compound from the blood. Control red blood cell units were prepared and stored as conventional leuko reduced additive system red blood cells. The stored, treated blood was then analyzed for measures of viability and metabolic activity, and subsequently labeled with a radioactive tracer and reinfused into the subjects. AuBuchon noted, "One of the key technical challenges in designing this study was to use a double, radio-labeled method to measure the survival of the infused red cells in circulation."

The researchers found that recovery of the treated red blood cells after 24 hours was comparable to that of the control units. The long-term survival of both treated and control blood appeared normal. All blood cell infusions were well tolerated by the volunteers. During the 28-day storage period, all units had less than one percent hemolysis, with the virally inactivated blood associated with a slightly greater rate of hemolysis. The treated blood units were associated with lower metabolic rates than the control units, as measured by glucose consumption, lactate production, and ATP concentration. After the treatment removal procedure, the researchers were unable to detect residual PEN110.

Study co-authors with AuBuchon were Constance A. Pickard, MBA, MT, Louise H. Herschel, MLT, and Jill C. Roger, MT, of Dartmouth-Hitchcock Medical Center, and Andre Purmal, PhD, John Chapman, PhD, and Kathleen Beach, MD, of Vitex (Watertown, MA). Additional contact: Harriet Ullman, Feinstein Kean Healthcare, (617) 577-8110 P hullman@fkhealth.com.

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