mpler Gene Therapy Envisioned for Some Forms of Dominant RP
Sept. 7, 2012 – Gene therapy for autosomal dominant retinitis pigmentosa (adRP) caused by defects in the gene RP1 may be easier to develop than was previously thought, thanks to a recent discovery by a Foundation-funded collaborative effort.
Previously, scientists believed that the RP1 gene therapy would require a two-step process: 1) suppressing expression of the defective copy of the gene; and 2) delivering a healthy, replacement copy. But in a research paper published online in the journal Public Library of Science ONE, researchers from the Massachusetts Eye and Ear Infirmary (MEEI) and Radboud University in the Netherlands found that the first step — disabling the defective copy of RP1 — was not necessary.
The study was led by Dr. Qin Liu of MEEI and Dr. Eric Pierce, chairman of the Foundation’s Scientific Advisory Board, director of MEEI’s Ocular Genetics Institute and associate director of the Berman-Gund Laboratory. Radboud researchers working on the study included Drs. Rob Collin, Anneke den Hollander and L. Ingeborgh van den Born.
In many autosomal dominant retinal conditions, the disease-causing gene leads to production of a mutant protein that can be toxic to retinal cells. To treat the disease, it is often not enough to only deliver a gene that expresses the healthy protein; the bad gene expressing the harmful protein needs to be suppressed, as well. However, the defective protein in RP1-linked disease was discovered not to be toxic.
“A one-step gene therapy process is much simpler to implement than one that involves two steps, so this is a beneficial advancement. It should get us to the clinic more quickly,” says the Foundation’s chief research officer, Dr. Stephen Rose. “Also, given that RP1 is the second-most prevalent gene linked to autosomal dominant RP, this finding is good news for many affected people.”
This discovery parallels the findings made by Foundation-funded researchers from the University of Florida who were investigating adRP caused by defects in the gene RHO. They were able to correct adRP caused by some mutations in RHO without suppressing expression of the bad gene. Defects in RHO are the leading cause of adRP. The University of Florida group received the 2011 Foundation Board of Directors Award for its finding and is working toward a clinical trial of its treatment.
Genable, a company in Ireland developing gene therapies for adRP, is planning to launch a clinical trial in 2014 of a gene therapy for adRP caused by defects in RHO. Its two-step approach would address all forms of RHO-linked disease. The company hopes to develop gene therapies for adRP caused by a wide variety of defective genes.
The MEEI team is currently developing an RP1 gene therapy in the lab. Dr. Pierce believes a future treatment will work for both autosomal dominant and recessive forms of RP caused by defects in RP1. |
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