A combination of gene therapy and tissue grafts could offer an improved way to repair ruptured tendons and ligaments, including common sports injuries such as season-ending knee and shoulder problems, according to a new study in mice.
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Tendons are difficult to repair surgically, but a strategy of implanting tendons that were loaded with genes to enhance recovery resulted in such significant improvements in injured mice that it could pave the way for future clinical trials in humans, said Hani Awad, a biomedical engineer at the University of Rochester Medical Center who led the study that was published online this week by the scientific journal Molecular Therapy.
The mouse model was intended to represent a common hand injury involving the rupture of the flexor tendon, which allows fingers to bend and straighten. The injury, which generally occurs when a hand is crushed or lacerated, affects millions of people each year. But the strategy could also be applied to other tendons and ligaments, such as the rotator cuff in the shoulder and the anterior cruciate ligament (ACL) in the knee.
“We believe this technology is a platform we can build on for treating other tendon injuries,” Awad said.
More animal studies remain to be done to work out the kinks, but he said clinical trials in humans could begin in the next three years.
A major problem with tendon injuries is that the natural healing process can form adhesions — scar tissue that prevents the tendon from gliding smoothly over joints. Patients can ultimately wind up with restricted movement, even with rehabilitation, Awad said.
In an effort to overcome the adhesion problem, his team began by freeze-drying tendons taken from healthy mice to remove all the water from the tissue. They then rehydrated the tendons using a solution containing viruses carrying a gene for a naturally occurring substance in the body called growth and differentiation factor 5 (Gdf5), which has been shown to enhance tendon healing.
The tendon tissue impregnated with the Gdf5-carrying virus was then implanted onto an injured tendon in the left hind feet of nine mice. The goal was to deliver the growth hormone gene directly to the injured area and encourage healing without the formation of adhesions.
The proof was in the animals' recovery. Mice that received the tendon with the Gdf5 gene developed fewer adhesions and showed significant improvement in foot function compared to animals implanted with tendons that lacked the gene. The animals' recuperation was tracked for 28 days after implantation, at which point the treated mice regained a level of mobility in their feet that was almost double that seen in animals that received the regular tendon. The tendons in the treated mice also glided more smoothly over the joint and provided more stability.
The researchers did not report any side effects in the animals from the treatment.
Awad said the technique could be put into use today. Tendons from human donors are available at tissue banks and the gene therapy virus, called recombinant adeno-associated vector, or rAAV, has been approved by the Food and Drug Administration for use in clinical trials.
Other researchers were enthusiastic about the potential of the technique for treating tendon and ligament injuries in people.
Dr. James Policy, director of sports medicine and an orthopedic surgeon at Children's Hospital & Research Center in Oakland, Calif., said if the strategy holds up in people “it would be a boon for orthopedic surgery beyond just hand injuries.”
The technique could be applied to ACL injuries and other conditions, he said.
One concern, however, is whether the gene therapy could induce cancer, Policy said. Several children have developed leukemia during a gene therapy experiment that cured their affliction with so-called “bubble boy disease,” when the virus used in the research — a different one than used in the tendon technique — tripped a cancer-causing gene.
Farshid Guilak, director of Duke University's orthopaedic bioengineering laboratory in Durham, N.C., who called the new research “a major advance,” said the technique may avoid some of the safety concerns about gene therapy because it localizes the delivery of the genes to a specific area rather than allowing them to spread all over the body. This might make the strategy safer and also might speed up its application in humans.
Steve Mitchell is a science and medicine writer in Washington, D.C. His articles have appeared in a variety of newspapers, magazines and Web sites, including UPI, Reuters Health, The Scientist and WebMD.
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