Recent Event Highlights: Phase-3 eye trials begin, Gene therapy for Parkinson's disease, Gene therapy for blood disease, Gene therapy for the brain, Gene therapy trials of eye disease, Dogs cured of blindness, and 5 more...
Created by VirginiaHughes on May 4, 2011
Last updated: 12/31/12 at 06:10 PM
Kathy High and Jean Bennett plan to launch phase 3 of the Leber's congenital amaurosis gene therapy trial, the last step on the long road to regulatory approval.
Kathy High published a mouse study of a fairly new gene therapy approach: rather than adding a healthy gene, a molecular knife—called a “zinc finger nuclease”—corrects the broken gene. The study is the first demonstration that zinc fingers can repair DNA not only in cells outside of the body, but also inside a living animal.
Researchers reported results from a double-blind and randomized trial of an AAV gene therapy injected directly into the brains of 45 patients with Parkinson's disease. Those who received the new gene experienced significant improvements on tests of gait, posture, and hand movements compared with those who underwent surgery without receiving gene therapy.
Researchers used the ex vivo gene therapy approach on an 18-year-old man with ß-thalassemia, a genetic disease that prevented him from making healthy red blood cells, which carry oxygen throughout the body. After receiving the gene therapy, he started making his own healthy blood.
French researchers reported positive results from an ex vivo gene therapy on two 7-year-old boys with X-linked adrenoleukodystrophy, a fatal brain disease caused by the loss of the ABCD1 gene. This gene is involved in producing myelin, the fatty sheaths that insulate neurons. Without ABCD1, the brain can’t send electrical messages properly. Two years after therapy, their brain cells had started making insulated neurons and the damage ceased. Although the boys still have some cognitive difficulties, the therapy saved their lives.
Kathy High and Jean Bennett enrolled 12 people (7 adults and 5 children) in a trial using AAV to fix the same rare vision disease they cure in dogs, Leber’s congenital amaurosis. At the same time, research groups in London and Florida, respectively, were doing similar trials. Patients in all three groups saw dramatic gains in vision after the treatment. Perhaps best of all, none had an immune reaction to the therapy. (Trial participant Corey Haas pictured)
Kathy High and Mark Kay reported the shocking results of one patient in their gene therapy trial for hemophilia. At first, the therapy worked exactly as it had in dogs: the clotting protein in the man's blood rose dramatically. But after four weeks, the protein levels began to drop, while liver enzymes—a sign of liver injury—began to rise. By 12 weeks, his enzyme levels were back to normal, and he had no detectable clotting factor in his blood. The researchers discovered later that his immune system was mounting a response to the AAV shell (virus pictured).
By the fall of 2002, 11 children with a rare immunodeficiency called SCID had enrolled in a gene therapy trial in France that used a retrovirus to fix their damaged gene. Nine had been cured. That November, however, one of the children developed leukemia (pictured). Eventually, four of the participants developed cancer (though all of them responded well to treatment).
Jean Bennett of the University of Pennsylvania reported that AAV gene therapy restores vision in a dog model of Leber's congenital amaurosis, a rare genetic disease that causes blindness in children.
18-year-old Jesse Gelsinger died after receiving a gene therapy for his rare metabolic disorder at the University of Pennsylvania. The therapy used a vector called adenovirus, which can trigger a serious innate immune reaction.
Kathy High's group and another team at Stanford University, led by Mark Kay, independently cured hemophilia B in dogs. Both groups used a new delivery method: they hijacked the outer shell of a virus, called adeno-associated virus (AAV), to carry a gene called clotting factor IX into the dogs’ cells.
'RNA interference' made a splash in 1998, when researchers inserted small, double-stranded pieces of RNA into worm cells. The fragments initiated a process to destroy matching sequences in the worm's messenger RNA, preventing them from being translated into protein. A few years later, the process was repeated in human cells. Voilà: a way to silence specific genes.
Ashanti DeSilva, a 4-year-old girl, received an ex vivo gene therapy to treat SCID, a rare immunodeficiency caused by the absence of T-cells (pictured, right). The therapy seemed to work: four years later, the girl carried the healthy gene in half of her white blood cells. From 1989 to 1998, some 275 other trials were listed in U.S. regulatory registries.