A Phase I Clinical Trial in Osteoarthritis Gene Therapy

Project: Research project

Project Details


Osteoarthritis is a disabling disease of joints that affects more than 27 million Americans. It is more common among military personnel, probably because of damage to their joints during training and active duty. Osteoarthritis is painful, incurable, and very difficult to treat. At the moment, osteoarthritis is treated by walking aids, physical therapy, painkillers (including, in severe cases, opiates), and the injection into the joint of a substance called hyaluronic acid that is suggested to serve as a lubricant. A number of non-Food and Drug Administration-approved approaches are also gaining popularity, such as the injection of preparations made from the patients' own serum. None of these are very effective and none of them stop the disease from progressing. Ultimately, many patients have no alternative to the major surgery that is necessary to implant an artificial joint. Research has discovered that a protein called 'interleukin-1' is present in joints with osteoarthritis, where it contributes to inflammation, pain, and destruction of cartilage. There is a naturally occurring protein known as the 'interleukin-1 receptor antagonist' that blocks interleukin-1. The interleukin-1 receptor antagonist could therefore be a powerful new drug against osteoarthritis. But it is very difficult to deliver to joints. It cannot be given as a pill because it is a protein and will be digested in the stomach. If injected into the blood stream or muscle, it does not reach the joint. If interleukin-1 receptor antagonist is injected into joints, it comes right back out again in a few hours. Thus, to be able to harness the therapeutic potential of interleukin-1 receptor antagonist, it is necessary to find a way to deliver it to joints in a manner that will keep it there for a long time. We have developed a way to do this based upon gene therapy. Gene therapy relies on the fact that the synthesis of proteins such as interleukin-1 receptor antagonist is directed by genes. In our gene therapy approach, the gene that directs the synthesis of the interleukin-1 receptor antagonist is introduced into the joint with osteoarthritis. Unlike proteins, genes introduced into the joint in this way are able to remain there for long periods of time -- months or years. While present and active, the interleukin-1 receptor antagonist gene will continue to direct the synthesis of the interleukin-1 receptor antagonist protein within the diseased joint for a long period of time. In this way, it will confer a sustained therapeutic effect. In order to introduce the interleukin-1 receptor antagonist gene into the joint in an effective manner, the gene is incorporated into a virus known as the adeno-associated virus. This virus causes no known disease and has been used for human gene therapy of a number of diseases. The virus containing the interleukin-1 receptor antagonist gene is called a vector. We have injected this vector into the knee joints of rats and horses to confirm that it is safe and able to treat osteoarthritis. We now propose a small study in nine human patients with osteoarthritis of the knee. This study will primarily address whether the vector is safe. Starting with a low dose, three patients will receive the vector by injection into the affected knee joint. If there are no safety issues, three additional patients will receive a medium dose of vector. If there are still no safety issues, three additional patients will receive a high dose of vector. Each patient will be followed for 1 year to confirm safety and to determine whether the gene is working.

Effective start/end date9/1/169/1/16


  • U.S. Army: $4,889,678.00


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.