Genetics sees the light

Laget Inc., along with UR staff, works on laser that activates genes

By Michael Wentzel
Democrat and Chronicle
Edward Schwarz, Michael Maloney and Paul Rubery, left to right, all UR professors, have formed a company that uses an ultraviolet laser to activate genes in the possible repair of bones damaged by degenerative disease. [Day in Photos]

(June 30, 2003) - If the scientists and physicians who make up a new company called Laget Inc. reach their goals, spine repair, degenerative arthritis and other diseases could be treated with the help of a little light.

Laget has licensed technology developed at the University of Rochester Medical Center, and most of the company's officers are on the university's faculty and surgical staff.

The technology uses ultraviolet laser light to activate therapeutic genes that would, for example, rebuild bones.

"A number of orthopedic companies have paid a tremendous amount of money for genes that can mediate a repair process, but they have no way to deliver these genes," said Edward M. Schwarz, president and founder of the company. "What Laget offers is a technology that can safely and effectively deliver their genes."

Gene therapy, however, remains controversial and experimental. Laget's plan is to form partnerships with medical device companies while research and development continues on the technology that Laget says addresses safety issues.

"We need more understanding of the molecular mechanism of this process. This is still a little bit like magic," said Schwarz, a UR associate professor of orthopedics.

The company is unlikely to become a manufacturer. But Laget will "generate know-how, a technology and a clinically viable technique to target genes that we will license to other companies," Schwarz said.

Gene therapy primarily involves inserting a "normal" gene that replaces an "abnormal," disease-causing gene. A molecule called a vector, which usually is a virus, is genetically altered to carry the normal gene and deliver it to a patient's target cells. Gene therapy also can be used to turn a gene on or off or increase its activity.

The U.S. Food and Drug Administration so far has not approved any human gene therapy product for sale. At least one person has died during a clinical trial and others have had serious reactions or side effects. The problems include controlling the delivery of the genes and the level of gene expression.

Laget's technology will use as a delivery vector an adeno-associated virus that Schwarz said is far safer than other viruses. The virus has a drawback, however; it delivers single-stranded DNA, which cannot cause gene expression.

Laget's laser, using the technology and ultraviolet wavelengths patented by the UR, provides a solution, Schwarz said. The laser light, delivered to the target area through fiber-optic cables, induces the production of specific enzymes that orchestrate the generation of a complementary strand of DNA. The synthesis of the combined DNA initiates the therapy.

The process safely confines the gene therapy to the target area, Schwarz said.

"The ultraviolet light is a way to turn on the mechanism," said Dr. Regis O'Keefe, Laget's chief clinical officer and a UR orthopedic surgeon and researcher.

"The dose is far less than sunburn and it is directed to a defined area. You would get less ultraviolet radiation than you would get on a walk to your car on a sunny day."

The process, for example, could be used to treat damage to articular cartilage, the spongelike substance that provides a protective layer to joints such as the knee. Time and activity can erode the cartilage, eventually causing swelling and pain in the joint.

Many with the problem require joint replacement.

Laget proposes using a therapeutic gene known to stimulate growth of articular cartilage.

"It would teach the cells to make new cartilage," said Dr. Michael D. Maloney, a UR orthopedic surgeon who is a member of the Laget team.

The process has worked successfully in cellular experiments and in bone grafting in mice, Schwarz said.

Laget plans animal experiments involving cartilage growth and spinal fusion to develop the evidence necessary for approval of human clinical trials.

The laser also must be adapted for use in different kinds of surgeries.

Laget initially will focus on diseases of the bone and bone repair. But the approach could be used to deliver therapeutic genes to treat cancer and cardiovascular disease, said J. Jeffrey Goater, Laget's chief executive officer.

Laget formed about 18 months ago, taking its name from the technology, "light activated gene transduction."

The company, which rents space at the university and Vaccinex Inc., a Rochester biotechnology company, announced licensing the UR technology this month.

The Laget team also includes Thomas Foster, UR professor of radiology, and Dr. Paul T. Rubery Jr., a UR associate professor of orthopedics and a spinal surgeon.

The company recently closed a successful financing round with "angel" investors, Goater said. The money will support development of a laser prototype.

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