gene therapy can cure blindness (15th gene discovered, spata7)

8/14/2019 Gene Therapy Can Cure Blindness (15th Gene Discovered, SPATA7)

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Gene Therapy can cure Blindness:15th Gene discovered

Abegail Rasco

Jenneli EspolitaAllen Espinosa



Vision loss and eye disease affect 3.6 million Americans and costthe United States $68 billion each year

Leber's congenital amaurosis (LCA)• first described in 1869 by Theodore Leber• rare retinal disease typically inherited in arecessive manner• inherited eye disease that appears at birth or in the

first few months of life• typically characterized sluggish or no pupillaryresponses, and severe vision loss or blindness



Retinitis pigmentosa- type of hereditary retinal dystrophy, a group of inherited

disorders in which abnormalities of the

photoreceptors or the retinal pigment epithelium (RPE)of the retina lead to

progressive visual loss

caused by mutations in the same gene

http://webvision.med.utah.edu/imageswv/DONFig12b.jpg

http://webvision.med.utah.edu/imageswv/DONFig12a.jpg



Linkage analysis, homozygosity mapping and candidate geneanalysis facilitated the identification of 14 genes mutated inpatients with LCA and juvenile retinal degeneration



In addition to these 14 LCA genes, two genetic loci (LCA3 at

14q24 and LCA9 at 1p36) have been identified, but theunderlying genes remain unknown.

The homozygous nonsense and frameshift mutations wasidentified in a positional candidate gene,SPATA7(spermatogenesis associated protein 7 [MIM 609868])by direct Sanger sequencing



• Study Subjects

• STR and SNP Genotyping and Sequencing• Homozygosity Mapping with SNP Arrays for Identificationof LCA and Juvenile RP Patients Whose Disease RegionOverlaps with LCA3• RNA In Situ Hybridization and Immunohistochemistry

SUBJECTS AND METHODS

RESULTS

• Fine Mapping of the LCA3 Locus• SPATA7 Is Another LCA and Juvenile RP Gene• Spata7 Is a Highly Conserved, Vertebrate-Specific ProteinExpressed in the Mature Retina



Koenekoop's team found SPATA7, the 15th gene in theillness.

SPATA7 is the first gene with a mutation that disrupts theprotein transport between two important compartments of

the cell: the endoplasmic reticulum and the Golgi apparatus.

All proteins in every cell have to pass through this transportpathway; thus SPATA7 plays a major role and its mutationmay affect many aspects of vision.



Because of its function in protein transport, the SPATA7 genealso identifies a new pathway, a cellular mechanism, whichopens the door to new treatment possibilities.

The research opens new

window to:

• specific cellular processes involved inblindness• increases the number of potentialtherapeutic targets

• improved diagnosis, treatments andcures• Gene therapy or treatments torestore sights using SPATA7 gene

example: LCA-RPE65 genetherapy



Stephen Howarth, 18, had a degenerative condition, caused by a faultygene, that had damaged the light-detecting retina at the back of his eyes.



Cure to other diseases

As a gene that is linked to multiple human diseases,SPATA7 offers opportunities for uncovering novelinsights into human pathogenesis



References

Wang, Hui, et al. (2009). Mutations in SPATA7 Cause Leber Congenital q

Amaurosis and Juvenile Retinitis Pigmentosa. The AmericanJournal of Human Genetics

den Hollander, Anneke I., et al. (2008). Leber congenital amaurosis: Genes,proteins and disease mechanisms. Elsevier

Vision and Gene Therapy. http://www.sfn.org/skins/main/pdf/rd/vision.pdf

http://www.sfn.org/skins/main/pdf/rd/vision.pdf

http://www.sfn.org/skins/main/pdf/rd/vision.pdf

gene therapy can cure blindness (15th gene discovered, spata7)

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