Tel Aviv researchers say studies of mice have advanced the possibility of using gene therapy to fix hearing loss, by counteracting the effect of a rare genetic condition found in Iraqi Jews.
Thousands of tiny mutations in human genes can seriously harm or eliminate the ability to hear. One such mutation in the SYNE4 gene, which harms the hair cells inside the cochlea of the inner ear, which are important for hearing.
Prof. Karen Avraham, vice dean of Tel Aviv University’s medical school, recently published a study showing that gene therapy in mice with the mutation “rescued” their hearing, building on earlier research and raising hopes of using the same methods on other mutations that affect hearing.
“After giving special gene therapy to newborn mice who were expected to be deaf because they had the SYNE4 mutation, they had perfect hearing at three weeks, which is when mice start hearing,” said Avraham. “We monitored the mice until 24 weeks, showing that we had actually averted the damage.”
In 2013, Avraham was part of a research team that first identified the SYNE4 mutation as a cause for hearing loss. The mutation has been identified in a small number of parents, all of whom have full hearing. When two carriers have a child together, the child has a 25 percent chance of high-frequency hearing loss, which is defined as a form of deafness.
The mutation has caused deafness among the children of just five families worldwide, two of which are Israeli, according to Avraham. But with mutations in over 120 genes known to cause some form of hearing impairment, the study is an important step in a broader international effort to use gene therapy to address human hearing loss, which is the most common neurological disorder.
According to the US Centers for Disease Control, 50% to 60% of hearing loss in babies or young children is due to genetic conditions.
“This work is bringing the use of gene therapy one step closer to alleviating hearing loss,” Avraham said.
Working with PhD student Shahar Taiber, Avraham sourced mice that had been engineered with the SYNE4 mutation, which subsequently became pregnant. When the baby mice were born, they administered the gene therapy.
“We injected them with a healthy gene that replaced the single unhealthy gene that was expected to cause deafness,” Avraham explained.
Avraham monitored the mice using hearing tests, and also with examinations of their cells, which revealed that the cells which normally cause hearing damage as a result of the SYNE4 mutation were not present.
“As opposed to CRISPR, where you ‘edit’ the gene, here you insert a healthy gene into the inner ear of the mice,” said Avraham. “So while the mice have a defective gene, this method essentially replaces it with a healthy gene, just after the mouse was born, and prevents the damage.”
The research was published last month in the peer-reviewed journal EMBO Molecular Medicine. Avraham noted this is not the first time that gene therapy has been used to address deafness in mice, as other mutations have been remedied with the same method.
Two years ago, Boston researchers reported that they had used gene therapy to restore hearing and balance in mice with some genetic inner ear disorders.
Researchers are hoping the studies of the mice will one day pave the way for proven gene therapies that can be used in humans.
“Our hope is that, in the future, we will be using this technology to help humans with mutations to this gene and others,” she added.
Prof. Wade Chien, a hearing specialist based at the John Hopkins School of Medicine, called the study “important,” in a statement distributed by Tel Aviv University.
“The magnitude of hearing recovery is impressive,” said Chien, who was not involved in the research.
“This study is a part of a growing body of literature showing that gene therapy can be successfully applied to mouse models of hereditary hearing loss, and it illustrates the enormous potential of gene therapy as a treatment for deafness,” he said.