Progress toward an alternative for EPO - Gas6 offers remedy where EPO fails today

31 January 2008
Many patients with a chronic disease or cancer have to contend with anemia − and the severe fatigue that accompanies anemia impedes the patient considerably in his or her daily activities. At present, the hormone EPO is administered to a large number of these patients to alleviate the anemia. But unfortunately, treatment with EPO is not always effective, and not all patients respond to this therapy. VIB scientists connected to the Katholieke Universiteit Leuven have been researching the role of the Gas6 protein. This substance has proven successful in the treatment of mice with anemia, without causing the side effects that the use of EPO entails. In addition, Gas6 contributes to a reinforcement of EPO’s effect. Gas6 might possibly form the basis for a new treatment for anemia and offer a remedy for patients where EPO is ineffective.
 
What is anemia?
When the blood contains too few red blood cells, or when the red blood cells contain too little hemoglobin, the condition is called anemia. Hemoglobin binds to oxygen from the lungs and conveys it throughout our bodies, where it plays an essential role in the body’s production of energy. If there are not enough red blood cells in our body, or if the red blood cells do not contain enough hemoglobin, then insufficient oxygen is transported. A shortage of oxygen in our tissues can cause people to feel tired and weak, and serious cardiovascular, neurological and musculoskeletal abnormalities develop.
 
EPO as the remedy
EPO (or Erythropoietin) is a hormone that is produced predominantly in the kidneys and that stimulates the formation of red blood cells. However, sometimes the kidneys do not produce enough EPO and anemia results. Such a shortage of EPO often occurs in patients with a chronic disorder (like kidney failure or rheumatoid arthritis) and in cancer patients. In the case of cancer, anemia can be caused by the disease itself as well as by chemotherapy.
 
When patients with chronic kidney ailments or cancer develop anemia, the human EPO protein is produced in mammalian cells and administered as a drug. The EPO then stimulates the formation of red blood cells, thus alleviating the anemia. But, in a large number of patients, the use of EPO as a remedy fails; in some patients, even high dosages of EPO are not effective.

Gas6 as alternative − and safer − remedy?
VIB researcher Diether Lambrechts and his colleagues have been studying − under the direction of Ed Conway and Peter Carmeliet, and in collaboration with foreign experts − the role of the Gas6 protein in mice. While EPO plays a prominent role in the production of red blood cells throughout our life, Gas6 is only involved in the production of red blood cells in adulthood.

 
When mice with anemia are treated with Gas6, the red blood cells once again rise to their normal levels in the blood. In contrast to EPO, the use of Gas6 does not result in an excessive production of red blood cells, which increases the risk of thrombosis. Furthermore, Gas6 reinforces the effect of EPO: indeed, when Gas6 is administered to mice that have not produced enough EPO, it works just as well as EPO, and a combined treatment of Gas6 and EPO produces an even greater therapeutic effect.
 
So, the positive evaluation of Gas6 in anemic mice raises hopes for a more effective and safer remedy for chronic disease patients who have to contend with anemia as a consequence of their disease or therapy.
 
Relevant scientific publications
This research appears in the authoritative journal The Journal of Clinical Investigation (Angelillo-Scherrer et al., Role of Gas6 in erythropoiesus and anemia in mice).
Other relevant publications that have preceded this research:
Angelillo-Scherrer A, et al.,
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
J Clin Invest. 115, 237-246, 2005.
Angelillo-Scherrer A, et al.,
Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis.
Nat Med. 7, 215-221, 2001.
 
Funding
This research has been funded by: the Dr. Henri Dubois Ferrière Dinu Lipatti Foundation, Swiss National Foundation for Scientific Research grants, the Belgian Federation Against Cancer, Bristol Myers Squibb Foundation, GOA, IWT, FWO and VIB.
 

Questions

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