Since news that researchers had restored sight in dogs with Leber congenital amaurosis (LCA) broke two weeks ago, Jean Bennett's phones at the F.M. Kirby Center for Molecular Ophthalmology at University of Pennsylvania's Scheie Eye Institute haven't stopped ringing. Anxious parents, whose infants suffer from this and other retinal degenerative diseases, want help. But they have to wait a few years; much more needs to be done. Researchers at Penn, Cornell University, and the University of Florida delivered a good copy of the gene defective in LCA, RPE65, to the right eyes of afflicted dogs using adeno-associated virus. Success was measured qualitatively with numerous response experiments, quantitatively using electroretinography, and molecularly using PCR and western blot analysis (G. Acland et al., "Gene therapy restores vision in a canine model of childhood blindness," Nature Genetics, 28:92-5, May 2001). Now, 10 months later, sight in the treated dogs' right eyes remains as strong as when first tested. The left eyes were left as controls. Bennett says future work includes examining immunological responses, optimizing the amount and target of the treatment, discovering treatment duration, and determining the time window during which it will be effective. "With this disease," Bennett says, "there is not a very fast rate of degeneration. I believe that there are other diseases that may have similarities ... and those may be the next likely targets for research." Bennett, who believes that human trials could begin in about three years, warns of lessons learned from the tragedy of Jesse Gelsinger, who died two years ago in a gene therapy trial at Penn, "You have to be careful extrapolating a human treatment from animal testing."
RU 486 to Combat Psychotic Depression
Preliminary trials involving the controversial abortion drug RU 486 (mifepristone) show promise in treating the hallucinations and delusions that accompany psychotic depression. Stanford University psychiatrists, conducting Phase I and Phase II clinical trials, found that RU 486 relieved these mental maladies within four days, says Stanford investigator Joseph Belanoff. RU 486 blocks the brain's receptors from receiving the hormone cortisol, which stays elevated all day in patients with psychotic depression. Normally, the hormone follows a daily rhythm. Belanoff comments that 35 patients were involved in the research; an estimated four million Americans suffer from this affliction. Treatment for psychotic depression has typically involved electric shock as well as anti-depressive and anti-psychotic medication, which takes from three to six weeks before it is effective. While RU 486 relieved the psychotic symptoms, Belanoff notes that it did not alleviate the depression. He adds that the drug's anti-psychotic efficacy is separate from its ability to induce abortions, which it does by blocking progesterone receptors. Belanoff has a five-patient, double-blind placebo study, in press.