A Pharmacological and Toxicological Evaluation of the Gene Transfer Vectors sc-rAAV2.5IL-1Ra (Rat) and scr-AAV2.5IL-1Ra (Human) in Rats

Osteoarthritis is a disease of the joints in which the cartilage that normally covers the ends of the bones, reducing friction between them, wears thin. The result is pain and loss of motion or flexibility, which can become debilitating. Osteoarthritis is the most common form of arthritis, affecting more than 25 million Americans. Women are at greater risk for the disease than men. No cure is known for osteoarthritis, but treatments exist for the pain. These scientists are developing a gene therapy for osteoarthritis, which will be injected into the affected joint. The resulting gene product works by blocking an inflammatory agent that contributes to the deterioration of the cartilage. This can allow the cartilage to heal, restoring function in the joint.

Scientific Synopsis

The services requested in this application form part of the development of a Phase I clinical trial in the gene therapy of osteoarthritis (OA) and are needed to support an Investigational New Drug (IND) application. The proposed clinical trial is based upon a considerable body of prior research by the PI and other key personnel in which they have developed technologies permitting gene transfer to joints in a manner that gives persistent intraarticular transgene expression. They have demonstrated an anti-arthritic effect in animal models when interleukin-1 receptor antagonist (IL-1Ra) is used as the transgene. Based on this, they have developed a clinical protocol in which a self-complementing, recombinant adeno-associated virus (AAV) vector, serotype 2.5, carrying human IL-1Ra cDNA (sc-rAAV2.5IL-1Ra) will be injected into the knee joints of human subjects with mid-stage OA.

A detailed description of this protocol was submitted to the Food and Drug Administration (FDA) as part of pre-Investigational New Drug (IND) discussions. After several conference calls and exchange of information, the FDA gave a clear statement of what further preclinical studies are required before going forward with an IND application. This application requests resources to carry out the studies required by the FDA.

Lead Collaborators

Mayo Clinic, Rochester, Minnesota
Christopher Evans, Ph.D.

University of Florida, Gainesville, Florida
Steven Ghivizzani, Ph.D.

University of North Carolina at Chapel Hill
Richard Samulski, Ph.D.

University of Pittsburgh
Paul Robbins, Ph.D.

Public Health Impact

Osteoarthritis is common, debilitating, costly and incurable. Because there is no effective treatment, it severely reduces the quality of life of millions of Americans. Gene therapy offers a novel approach to the treatment of osteoarthritis, and this proposal seeks services that are necessary before a human trial can begin.


Work on this project is complete. The investigators used BrIDGs data to file an IND application that was cleared by the FDA.

Project Details

  • Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies
  • IND-directed toxicology


Safety and Biodistribution Assessment of sc-rAAV2.5IL-1Ra Administered via Intra-articular Injection in a Mono-iodoacetate-induced Osteoarthritis Rat ModelMolecular Therapy — Methods & Clinical Development • Jan. 13, 2016