La Jolla Institute forms partnership to investigate potential new therapy for sickle cell disease

May 02, 2017

An inherited disorder, sickle cell disease primarily affects those of African descent and Hispanics of Caribbean ancestry, but the trait has also been found in those with Middle Eastern, Asian, Indian, Latin American, Native American, and Mediterranean heritage.

In the U.S., it is estimated that more than 70,000 people, primarily African-Americans, are affected by the disease. Sickle cell disease occurs in individuals who inherit two copies of the sickle cell gene-one from each parent. Millions worldwide are estimated to suffer complications from sickle cell disease.

The trial will begin in adults with sickle cell disease but no painful crises, giving different test doses of Lexiscan for periods of 12 and 24 hours to ensure that it does not cause toxicity. Pending these results, the team will then move to test Lexiscan in adults with pain crises and acute chest syndrome, and, in the second year, in children age 14 and older.

Dr. Nathan, who for three decades led the Division of Hematology at Children's Hospital Boston and later the joint Hematology and Oncology program of Children's and Dana-Farber Cancer Institute, hopes Lexiscan will reduce the severity of life-threatening acute chest syndrome. "Pulmonary complications of sickle cell anemia can be fatal, because patients are unable to breathe," he said. "We want to see if the drug will abort pulmonary injury. We do know that it works very well in sickle cell mice with pulmonary disease," he said referring to Dr. Linden's ongoing adenosine research.

In his studies, Dr. Linden not only showed that adenosine significantly reduced inflammation and pulmonary defects in mouse models of sickle cell disease, he also pinpointed the specific white blood cells causing the inflammation, known as invariant natural killer T cells or iNKT cells.

Dr. Linden, working in conjunction with Joshua Field, M.D., a hematologist from Washington University, found that patients with sickle-cell disease have significantly elevated numbers of activated iNKT cells. "This further validated that inflammation plays a major role in this disease," he said.

Source: La Jolla Institute for Allergy and Immunology