Gene Therapy And Usher Syndrome

The Promising Results in Using Gene Therapy to Treat Usher Syndrome Patients

Gene therapy has advanced considerably in recent years, due particularly to mutant mouse models genetically modified to mimic the effects of health problems like deafness and help test effective treatments.

Various studies published this February in Nature Biotechnology showed the progress researchers have obtained in delivering the appropriate genes to cells in the inner ear and help improve the level of hearing in laboratory mice. The main actions studied here involved transduction results in mice, described thoroughly in two scientific papers: “A Synthetic AAV Vector Enables Safe and Efficient Gene Transfer to the Mammalian Inner Ear” and “Gene Therapy Restores Auditory and Vestibular Function in a Mouse Model of Usher Syndrome Type 1c.”

Gene Therapy and Hearing Improvements

The work is based on studies conducted in 2015 at Harvard Medical School and the Boston Children’s Hospital, and involved hearing restoration treatments. Scientists have reported helping mice achieve improved sensitivity to sound as quiet as 25 decibels using an enhanced version of the therapy vector developed by Massachusetts Eye and Ear.

Complex auditory function restoration was achieved with the use of the Anc80L65 synthetic vector, targeting hair cells at higher rates and surpassing the effects obtained through older vectors. Genes were transferred efficiently to outer hair cells for the first time ever through this technique.

The mouse study was led by Gwenaëlle Géléoc, Ph.D., from the Boston Children’s Hospital, and involved the use of Anc80 to correct specific genes responsible for the Usher syndrome, a genetic form of deaf-blindness. According to researcher Konstantina Stankovic, M.D., Ph.D, the technique was used successfully to alter cells in the inner ear, which also led to improving balance functions impaired by the syndrome.

Dr. Géléoc pointed out that, through the Anc80 viral vector a high percentage of 80-90% of sensory hair cells were successfully transduced, leading to gene and protein expression recovery, the restoration of cell function and the recovery of hearing through the restoration of outer hair cells, which have the role to amplify the signal sent to the brain. Auditory and vestibular function were restored to an unprecedented level.

The Impressive Results of the Study

Mice with a mutation in Ush1c were studied. The mutation leads to a protein known as harmonin to lose its function, leading to the sensory cells’ deterioration. A corrected Ush1c gene has led to the hair cells developing normal, full-length harmonin which improved hearing, and restored it even in mice that were deaf since birth.

From the 25 mice used, 19 were shown to hear sounds lower than 80 decibels, while some heard even sounds as low as 25-30DB. The gene therapy also resulted in improved balance, as treated mice stood on a rotating rod for a longer time without falling.

With over 100 genes responsible for hearing impairment in humans, the study is a landmark breakthrough for curing major hearing problems. Much work is still required, as the therapy has only proven to be effective when used right after birth – a delay of 10-12 days rendering it ineffective. The study also did not account for the vision problems caused by the Usher syndrome, although gene therapy has already proven effective in the case of other causes of blindness.

Another senior author of the vector study, Luk H. Vandenberghe, Ph.D, concluded that the therapy has shown promising results for future research in hearing gene therapy, and there are hopes to tackle both the blindness and hearing aspects of the syndrome through future efforts.

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