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Validation of the disease model  and therapy for retinitis pigmentosa 11

Validation of the disease model and therapy for retinitis pigmentosa 11

Objective

With a prevalence of 1 in 3500 retinitis pigmentosa (RP) is a significant cause of blindness in the Western world. RP is a group of hereditary retinal disorders, for which there is no effective treatment. It is mostly caused by mutations in genes related to the biochemistry of photoreceptors. PRPF31, however was the first ubiquitously expressed gene implicated in this disorder. Mutations in this gene are responsible for one of the commoner forms of autosomal dominant RP (RP11) with implications for a significant proportion of patients. Overall it has been noted that patients who manifest the disease present a severe form of retinal degeneration, often losing vision completely by the third decade. With the cloning of PRPF31, a novel class of genes, i.e. splicing factor genes, causing RP was revealed (PRPF3, PRPF8, PAP-1). These four genes are associated with a common splicing complex, U4/U6.U5 snRNP, and they are likely to share the molecular mechanism of the pathology. It has been noted that in families affected by PRPF31 mutations, manifestation of the disease is also dependent on the expression level of the wild-type PRPF31 allele. Thus, high levels of wild-type PRPF31 protein, can override the effect of mutant copy of the PRPF31 gene. This is known as partial penetrance and can be viewed as nature’s way of curing the disease. Learning from the clinical data, I would like to establish an RP11 animal model to validate the therapeutic effect of increasing PRPF31 expression. At first instance, Prpf31 levels in mouse will be reduced with RNA interference (RNAi) technology and the course of the disease progression will be assessed. The RNAi will be administered by subretinal injections. Subsequently, the rescue of the retinal phenotype will be brought about with delivery of the wild-type copy of the Prpf31 gene in AAV2/5 vector.
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Coordinator

UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6

Address

Place Jussieu 4
75252 Paris

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 45 000

Administrative Contact

Ella Bouquet (Ms.)

Project information

Grant agreement ID: 231125

Status

Closed project

  • Start date

    18 May 2009

  • End date

    17 May 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 45 000

  • EU contribution

    € 45 000

Coordinated by:

UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6

France