by Tom Hoglund
The January 11  issue of Time magazine carries extensive coverage of genetics and gene therapy research. In this issue, Dr. James Wilson, a gene therapy researcher from the University of Pennsylvania, states that he, "...expects Phase 1 clinical trials using AAV (adeno-associated virus) to begin later this year, first for the treatment of hemophilia and then later for a form of muscular dystrophy, a liver metabolic disease and retinitis pigmentosa, an eye disorder."
The AAV vector mentioned in this quote is a genetically altered virus capable of delivering therapeutic genes or genetic information to retinal cells. Until recently, continued progress in gene therapy was hindered by the lack of safe and effective vectors. However, in the last two years scientists have developed a new generation of vectors that show great promise in treating retinal degenerative diseases. Vision researchers are currently testing these new vectors in laboratory studies of gene therapy.
Dr. Jean Bennett, a Foundation-supported researcher from the University of Pennsylvania, who collaborates with Dr. Wilson, is testing the AAV vector in gene replacement therapy experiments. Gene replacement therapy is intended to prevent vision loss by delivering healthy genes to patients with recessive forms of retinal degeneration. Dr. Bennett was the first researcher credited with using gene replacement therapy to halt vision loss in an animal model with retinal degeneration.
Currently, Dr. Bennett and other Foundation researchers are refining gene replacement therapy techniques. Drs. Rajendra Kumar-Singh and Debora Farber, from The Foundation's Research Center at UCLA, developed a promising new vector, called an encapsidated adenovirus minichromosome (EAM). This new vector seems to have also eliminated the harmful genetic information while still retaining powerful gene delivery capabilities. In gene replacement therapy experiments with rodents, the EAM vector has safely delayed vision loss for long periods of time.
The Foundation also supports other gene therapy techniques. Dr. Tiansen Li of Harvard Medical School is using the AAV vector to deliver genes that might prevent or delay apoptosis. Apoptosis, or programmed cell death, is a genetically controlled process that causes degenerating photoreceptor cells to commit suicide. Preventing or delaying apoptosis may preserve vision. Because apoptosis is common to all retinal degenerative diseases, this form of gene therapy might one-day offer a universal treatment for retinal degenerations.
Drs. William Hauswirth and Alfred Lewin, Foundation-supported scientists from the University of Florida, recently reported dramatic success using the AAV vector in ribozyme gene therapy experiments. Ribozyme gene therapy is a form of gene therapy for dominant retinal degenerative diseases. In experiments with rodents, photoreceptor cell function was as much as 93 percent greater in the ribozyme-treated eyes than in the untreated control eyes. Dr. Hauswirth is now testing the safety and efficacy of this treatment in larger animal models. If these studies are successful, Dr. Hauswirth plans to seek FDA approval for phase 1 clinical trials of ribozyme therapy. Dr. John Flannery, a Foundation scientist from the University of California at Berkeley, who collaborates with Drs. Hauswirth and Lewin on ribozyme gene therapy, also evaluates gene replacement therapies for recessive disease.
It is difficult to predict exactly when pre-clinical safety and efficacy studies will be completed, when applications to the Food and Drug Administration (FDA) will be submitted, and when the FDA will grant approval for phase 1 clinical trials to test the safety of gene therapy in humans. However, Dr. Wilson's quote lends the sense that, with a new generation of promising vectors in hand, gene therapy has turned a corner and is heading to clinical trials for a variety of diseases, including retinal degenerations.
For further information, see Future Gene Therapy Possible For Inherited MD Patterns