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Saturday, March 18, 2000

Gene therapy to benefit future orthopaedics

For tissues with low healing potential, such as cruciate ligament ruptures and cartilage lesions, a combination approach of gene therapy and tissue engineering could lead to sufficient treatments, according to Freddie H. Fu, MD, chairman, Department of Orthopaedic Surgery, University of Pittsburgh.

Yet at this time, orthopaedics is quite underrepresented in that research milieu. Of the 396 gene therapy protocols active today, only one trial is for orthopaedics. Most (252) are in the field of oncology. However, AAOS members shouldn't be discouraged, said Dr. Fu, who noted the plethora of potential targets, including the meniscus, muscles, cartilage and bone.

"The lessons being learned from all these trials are extremely important for orthopaedic surgery," Dr. Fu said at a symposium March 17, 2000.

Most common orthopaedic problems are transient, and thus perhaps more ideally suited to a gene therapy solution that promotes quick healing, rather than chronic diseases that might require lifelong supply of growth hormone or other factors. The latter may prove to be quite challenging to address in a gene therapy context.

Last year, University of Pitts-burgh researchers completed the first gene therapy trial for a common, non-fatal disease: rheumatoid arthritis in elderly patients. The trial established data regarding the longevity of the biologic intervention, but more importantly, it showed for that the procedure is safe in human beings.

Dr. Fu said he hopes the data from trials such as this can be used to convince the FDA and NIH of the importance of launching and funding trials in younger subjects. But the investigator could be up for increased scrutiny in the wake of the widely-publicized first gene therapy-related death at the University of Pennsylvania.

In that case, the adolescent patient who died had ornithine transcarbamylase deficiency. He received a very high dose of the virus that was used as vector to get the genes to the liver that led to a severe reaction and liver failure. "That's something we will never even come close to in orthopaedic surgery" since the viruses could be more transient and administered in lower doses, said Dr. Fu.

Dr. Fu encouraged his colleagues to brush up on the principles in biology, noting that at the Orthopaedic Research Society earlier this week, some 80 percent of papers presented dealt with some sort of biologic process. "We have to think biologically in the year 2000, because only through biologic intervention can you have novel orthopaedic treatment options," he said.

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Last modified 18/March/2000 by IS