Gene therapy might stimulate cartilage regeneration

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Gene therapy might stimulate cartilage regeneration



May 17, 2006



Gandey



Rochester, NY - An early study has demonstrated for the first time

that light-activated gene therapy may play an important role in

treating superficial articular defects and meniscal tears [1]. In the

April 2006 issue of the Journal of Bone and Joint Surgery,

researchers say the new approach can specifically target the edge of

damaged cartilage while leaving nearby tissue untouched. " This

procedure is designed to dovetail with standard arthroscopic

procedures, which currently leave the defect unrepaired, " senior

author Dr Schwarz (University of Rochester Medical Center, NY)

told rheumawire. He says the new approach is designed to stimulate

cartilage regeneration.

The group is looking to mimic the process seen in lower vertebrates

such as reptiles and fish, which can regrow amputated skeletal

elements, including articular cartilage. " We want to understand how

regenerates can do what we cannot do, " Schwarz explained. " They do

not have a unique set of genes. We have them, but for some reason, we

use them only in the embryonic stage of early development. In

adulthood, we can't turn them on. "

Schwarz and his team studied the safety and efficacy of long-

wavelength ultraviolet laser light to induce light-activated gene

therapy in articular cartilage cells. Given the safety concerns of

short-wavelength light, the group focused on a long-wavelength system

that they say is less likely to cause cytotoxity.

Similar to previous studies, the current animal model found

recombinant adeno-associated virus to be highly efficient at turning

on gene therapy in articular chondrocytes. Studying rabbits, the

researchers, led by Dr Maloney (University of Rochester

Medical Center, NY), found that pretreatment with 6000 J/m2—a

standard dose of UV light—led to a 10-fold increase in the effect of

gene therapy in target cells after one week. In addition, nearly half

of cells exposed to the light expressed the inserted therapeutic gene.

Risk of delayed radiation fibrosis

In a news release about the study, the authors say this is the first

demonstration that site-directed gene delivery can safely and

effectively treat articular defects in higher-animal cartilage cells.

" It is our belief that our findings give promise for a future advance

that would provide a means for regeneration of articular cartilage to

an injured or degenerative joint. "



" Future studies should address the long-term effects of the long-

wavelength UV treatment. "



Maloney and colleagues point out that future studies should address

the long-term effects of the long-wavelength UV treatment and how

long target gene expression persists. " Here we show that there is no

significant evidence of articular chondrocyte apoptosis after one

week, " they write. " Considering that this programmed cell death is an

immediate response to environmental stress, it is inconceivable that

UVA could induce apoptosis after seven days. " But it is also

possible, they add, that this treatment could induce delayed

radiation fibrosis. They call for further investigation.

During an interview with rheumawire, Schwarz called this a first step

in a million-mile journey. He pointed to a number of potential

problems with efficacy and says scientists have yet to identify how

many genes are involved in the repair process.

But he hopes that this approach will one day be useful in treating

musculoskeletal-related disorders and might eventually play a role in

delivering therapeutic genes to treat cancer and cardiovascular

disease. Schwarz emphasized the endless possibilities of bona fide

tissue regeneration.

Maloney MD, Goater JJ, Parsons R, et al. Safety and efficacy of

ultraviolet-a light-activated gene transduction for gene therapy of

articular cartilage defects. J Bone Joint Surg Am 2006; 88:753-761.

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http://www.jointandbone.org/viewArticle.do?primaryKey=699563