Gene editing shows promise in treating inherited kidney disease

DNA genomics precision medicine
Newcastle researchers used a synthetic strand of DNA to trick cells into bypassing a kidney-damaging mutation. (Pixabay)

Joubert syndrome, an inherited brain disorder that affects one in 80,000 newborns, causes kidney failure in about a third of patients, many of whom end up requiring a transplant or dialysis. This inherited form of kidney disease is caused by a mutation in the gene CEP290, and now scientists in the U.K. say they have early proof that a form of gene editing called “exon skipping” can correct the error.

Researchers at Newcastle University used a synthetic strand of DNA to trick cells into bypassing the damaging CEP290 mutation, they reported in the Proceedings of the National Academy of Sciences. They used kidney cells from a 19-year-old patient with Joubert syndrome for their early testing of the technique.

They went on to try exon skipping in a mouse model of Joubert syndrome, as well as rodents with kidney cysts and kidney failure. The technique halted kidney disease in those models, they reported.


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“The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment,” said John Sayer, Ph.D., a consultant nephrologist at Newcastle Hospitals NHS Foundation Trust, in a statement. “This work paves the way towards [personalized] genetic therapies in patients with the inherited kidney disease.”

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Exon skipping has primarily drawn attention in Duchenne muscular dystrophy (DMD). It is the basis of Sarepta’s FDA-approved treatment Exondys 51, which is aimed at a subset of patients with a form of the disease that response to exon 51 skipping. The technology has run into some development difficulties, however. Earlier this year, Daiichi Sankyo released data on its exon-45-skipping DMD drug DS-5141b that raised efficacy questions. That drug is in a developing class known as antisense oligonucleotides.

Several research groups are now examining the emerging gene-editing system CRISPR-Cas9 in the treatment of DMD. They include scientists at Exonics, a startup that’s using an RNA guide molecule to deliver CRISPR into cells and skip 4 exons, which they believe will help 35% of patients with DMD. Ultimately they say their CRISPR method will be able to reach 80% of patients.

Sayer’s team at Newcastle is now looking for a drug company to help them formulate their exon-skipping technology into a compound that can be tested in patients with Joubert syndrome. They are planning to start human trials within three years, they reported.

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