NEW YORK -- October 24, 2009 -- Gene therapy can improve the eyesight of people, especially children, who have extremely poor vision or are virtually blind due to a genetically-inherited sight disorder. Furthermore, the improvement remained stable during 2-years of follow-up. The findings are reported in an article published Online First (www.thelancet.com) and in an upcoming edition of The Lancet, The findings also were reported at the 2009 joint meeting of the American Academy of Ophthalmology and Pan-American Association of Ophthalmology (AAO-PAAO).
One of the most severe forms of inherited retinal degeneration is Leber congenital amaurosis (LCA), which is a group of diseases that are caused by mutations in any one of at least 13 genes. Patients with LCA have severe loss of vision and abnormal eye movements in early infancy and during early childhood. There is no treatment for LCA and severe visual impairment during childhood usually progresses to total blindness by the third or fourth decade of life. The form of LCA in this study is rare: In the United Sates, approximately 5 babies each year are born with the condition. This disease was selected for study because proof-of-concept of gene therapy had been established in animal models, the gene had been cloned, the cellular degeneration in this disease is fairly slow thereby providing a reasonably large window of time in which to intervene, and success in this disease could pave the way for development of gene-based treatments for other more common retinal degenerative diseases.
In this phase 1 study, Jean Bennett, MD, PhD, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, and colleagues from the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, assessed the effect of gene therapy on retinal and visual function in children and adults with LCA. The study looked at 12 patients aged 8-44 years, each of whom had genetic material essential for correction of LCA injected into the eye which had the worst vision. The genetic material was carried by a virus (adeno-associated virus) which delivered the genetic material to the diseased cells in the eye.
The treatment was well tolerated by all the patients and resulted in an improvement in both subjective and objective measurements of vision. Patients had an increase of least 100-fold in pupillary light response and an 8-year-old child developed nearly the same level of light sensitivity as that in normal-sighted individuals. The greatest improvement was noted in children (aged 8, 9, 10, and 11), all of whom gained ambulatory vision.
"All 12 patients given gene therapy in 1 eye showed improvement in retinal function. The effect was stable during follow-up," the authors reported. "The results support our hypothesis that the response to subretinal gene therapy depends on the extent of retinal degeneration and, therefore, the age of the patient."
They add: "The most noteworthy result was the ability of children to navigate an obstacle course independently and accurately, even in dim light. … The visual recovery noted in the children confirms the hypothesis that efficacy will be improved if treatment is applied before retinal degeneration has progressed. Assessment of whether the treatment alters the natural progression of the retinal degeneration will be possible in follow-up studies."
In conclusion, they said that the success of this gene therapy in children "provides the foundation for gene therapy approaches to the treatment of other forms of LCA and of additional early onset retinal diseases."
In an editorial accompanying the study, Frans P. M. Cremers, PhD, and Rob W. J, Collin, PhD, both of Radboud University Nijmegen Medical Centre, Netherlands, write that this study "will further boost gene therapy trials and provide hope for patients with inherited blindness and other genetic disorders. As novel therapeutic strategies are being developed for each of the separate genetic defects, ascertaining and genotyping the corresponding patients will be the real challenge in the coming decade."
SOURCE: The Lancet
E-Mail this DGNews to a colleague
