Research Projects
The Musculoskeletal Gene Therapy Research Laboratory at Mayo Clinic studies joint diseases such as osteoarthritis, and bone and tendon healing and cartilage repair after musculoskeletal injuries.
Specific research projects being studied by Dr. Evans and his lab team include:
- A phase I study evaluating the safety of intra-articular sc-rAAV2.5IL-1Ra in patients with moderate osteoarthritis of the knee
- Healing of critical size segmental defects in bone by gene transfer
- Healing of critical size segmental defects in bone using chemically modified RNA
- Improved tendon healing by administration of growth factors
- Enhanced repair of defects in cartilage by gene transfer
Here's a closer look at the lab's research on osteoarthritis and musculoskeletal injuries.
A phase I study evaluating the safety of intra-articular sc-rAAV2.5IL-1Ra in patients with moderate osteoarthritis of the knee
The lab plans to initiate a phase I clinical trial to determine the safety of three different doses of a vector, sc-rAAV2.5IL-1Ra, delivered by intra-articular injection into one knee joint of nine patients with moderate osteoarthritis of the knee.
The vector transfers a gene encoding an anti-arthritic protein, the interleukin-1 receptor antagonist (IL-1Ra), to cells within the joint. These cells then produce IL-1Ra for an extended period of time, with the expectation of producing a sustained anti-arthritic effect. This vector has been shown to be safe and effective in preclinical testing.
Patients in the trial are followed for one year to assess safety, dosing and, in a preliminary manner, efficacy. This study is not yet open for patient recruitment.
Funding for the lab's knee osteoarthritis project is provided by the U.S. Department of Defense and Mayo Clinic's Transform the Practice initiative.
Read more from Mayo Clinic about Dr. Evans' knee osteoarthritis clinical trial.
Healing of critical size segmental defects in bone by gene transfer
Although fractures normally heal on their own, they don't if a large segment of bone is missing. Bone lesions that are too large to heal spontaneously are known as critical size defects. These bone (osseous) defects are typically treated by a procedure in which bone is taken from elsewhere in the body, usually the pelvis, and placed in the defect.
While this treatment for bone defects can be effective, obstacles include considerable donor-site morbidity and limited supplies of autologous bone for harvesting. Allograft bone also is available, but this is dead bone that lacks intrinsic regenerative capacity.
Research in the Musculoskeletal Gene Therapy Research Lab aims to provide new, reliable and inexpensive ways to treat large osseous defects.
One research strategy uses adenovirus vectors to transfer osteogenic genes to fragments of fat and muscle that are then implanted into the bone defect. This approach shows efficacy in a small animal model. Dr. Evans' lab is investigating whether immunomodulation can further improve outcomes.
Healing of critical size segmental defects in bone using chemically modified RNA
In collaboration with colleagues at the Technical University of Munich in Munich, Germany, the lab is developing new strategies for bone healing based on the delivery of messenger RNA (mRNA) rather than DNA.
The mRNAs are chemically modified to enhance stability, reduce toxicity and lower immunogenicity. The lab is evaluating a chemically modified RNA encoding bone morphogenetic protein 2 (BMP-2) in an animal model.
Improved tendon healing by administration of growth factors
In collaboration with researchers at the University of Basel in Basel, Switzerland, preclinical studies in the Musculoskeletal Gene Therapy Research Lab have shown that healing of the Achilles tendon is improved by implanting a collagen sponge and further improved if the sponge is first impregnated with purified, recombinant growth factors.
To make these observations more clinically relevant, Dr. Evans and his research team are evaluating sponges impregnated with autologous-conditioned serum and platelet rich plasma in an animal model of Achilles tendon transection. Healing is assessed by morphometry, histology and mechanical testing.
Enhanced repair of defects in cartilage by gene transfer
Cartilage is frequently injured, but it has no capacity for spontaneous repair. There are a number of surgical repair techniques for cartilage injury, but these have disadvantages that include cost, invasiveness and unreliable long-term outcomes.
Research in the Musculoskeletal Gene Therapy Research Lab aims to develop new, reliable and inexpensive ways to restore cartilage.
The lab's strategy is to deliver vectors encoding chondrogenic factors, such as transforming growth factor-beta, to sites of cartilage damage within plugs of clotted bone marrow. This research approach is being tested in an animal osteochondral defect model.