Sickle cell anemia is a disease that affects 2.6% of
Americans. It is an inherited disease in which the red blood cells
become c-shaped (sickle-shaped) due to abnormal hemoglobin in the cells.
Normally, red blood cells are round and smooth, and carry oxygen
throughout the body. In people with sickle cell disease, the abnormal
cells stick to one another causing blocked blood flow. The lack of
oxygen caused by these blockages damages organs and tissues and can
cause anemia, increased infections, pain, and even death. Current
treatments are limited and are unable to prevent the intense periodic
episodes of pain, or the long-term organ damage common to sufferers.
Infants and young children are especially at risk for increased
infections, stroke and heart attack.
In the United States, sickle cell disease most commonly occurs among African-Americans and Hispanic-Americans. About 1 in every 500 African-Americans and about 1 in every 1,000 to 1,400 Hispanic-Americans has sickle cell disease, according to the Centers for Disease Control and Prevention. Sickle cell disease also affects people of Arabian, Greek, Maltese, Turkish, Italian, Sardinian and Indian ancestry.
At the La Jolla Institute, Joel Linden, Ph.D. is making strides in the pursuit of new treatments for sickle cell disease. Linden is an expert in adenosine receptors, which are proteins on the surface of cells that recognize certain molecules that reach the cell surface and trigger a response. Adenosine is produced as a biproduct of the breakdown of adenosine triphosphate (ATP), which is like the gasoline of the cells.
Linden has found that adenosine levels rise when a cell is stressed and causes blood vessels to dilate, keeping oxygen levels in sync with delivery to the body’s cells. Linden and his lab are applying his findings to the immune system and a particular type of adenosine receptor called A2A. “We believe that activating adenosine receptors to inhibit inflammation has a lot of potential uses in inflammatory diseases such as sickle cell disease,” said Linden.
In particular, Linden found that when a person with sickle cell disease has blocked blood flow due to red cell sickling, and then restoration of blood flow (called ischemia reperfusion injury), certain immune cells get activated, especially natural killer t-cells (NKT). Basically what happens is the body inappropriately responds to the event by sending out immune cells to kill what it thinks is an infection or foreign invader. But over time, the NKT cells can damage the organs and tissues, causing lesions, and ultimately shortening the life span of sufferers.
Linden hopes that his research in adenosine could be used to block this immune response in sickle cell disease patients, in that many of the anti-inflammatory effects of adenosine are actually due to their ability to inhibit NKT cells. Linden’s lab is in pursuit of two new treatments for sickle cell disease, with one already in clinical trials.
“Very little progress has been made in treating this devastating disease for several decades. I think our new approach has great promise” said Linden.
