Supplements may delay genetic hearing loss in children

The study found that an antioxidant routine of beta carotene, vitamins C, E and magnesium (ACEMg) that are present in everyday foods and food supplements helped slow progression of hereditary deafness in mice with a connexin 26 gene deletion.

However, the enhanced diet had the opposite effect on another mouse model with the AUNA1 mutation. AUNA1​​ is a very rare form of progressive hearing loss with late onset in humans, typically developing in the second decade of life.

Gene mutations are a leading cause of genetic hearing loss in many populations. According to the World Health Organisation (WHO) over 360m people have disabling hearing loss. 80% of these people reside in low- or middle-income countries.

In Europe, about 52m people are affected and more than 50% of European adults over 65 present slight to severe hearing loss according to 2010 estimates.

Newborn screening test​

According to the researchers from the University of Michigan’s Kresge Hearing Research Institute and C.S. Mott Children’s Hospital, babies born with a genetic mutation that causes deafness pass their newborn screening test but then lose their hearing later in life.

“These patterns suggest that for some children, there may be an opportunity to potentially save cells present at birth. For these cases it’s crucial that we identify therapies that prevent progression and reverse loss of hearing,” ​said author Dr Glenn Green, associate professor of paediatric otolaryngology at C.S. Mott Children’s Hospital.

To assess the potential for treating GJB2 (the gene that encodes the protein connexin 26 and other forms of hereditary hearing loss) with ACEMg, the team tested the influence of the ACEMg diet on the cochlea and hearing of mouse models for two human mutations: GJB2 and DIAPH3.

The AUNA1 mutation leads to overexpression of the DIAPH3 protein​​ that causes profound abnormalities leading to auditory loss​.​

One group of mice modeling GJB2 received the ACEMg diet starting shortly after they were weaned (4 weeks) until 16 weeks of age.

Another group of GJB2 mice received ACEMg in utero and after weaning. The ACEMg diet was given to mice modeling DIAPH3 after weaning (4 weeks) until 12 weeks of age. Control groups received food pellets without the ACEMg supplement.

The team found that ACEMg supplementation influenced the progression of genetic hearing loss. The hearing thresholds measured by auditory brainstem response were significantly better for GJB2 mice fed ACEMg than for the control diet group. In contrast, DIAPH3 mice displayed worse thresholds than the control group.

“Our findings suggest that a particular high dose of mineral and vitamin supplements may be beneficial to one genetic mutation,”​ commented senior author Dr Yehoash Raphael, professor in the Department of Otolaryngology-Head and Neck Surgery at the University of Michigan Medical School.

“However, the negative outcome in the AUNA1 mouse model suggests that different mutations may respond to the special diet in different ways.”​

Antioxidant efficacy

Antioxidants have been shown to reduce the impact of oxidative stress in neuronal disorders, cancer, heart diseases and inflammatory diseases. Antioxidant treatment has also been shown to preserve gap junctions, which are the cellular components directly impacted by loss of connexin 26.

This research and its observations closely mirror a case study​​ carried out by the University of Michigan last year in which the same food supplements not only stopped the progression of hearing loss, but also resulted in a small hearing improvement for a boy with a connexin 26 mutation.

“These findings are encouraging for those of us who treat children with progressive connexin 26 hearing loss, and possibly for other mutations not yet tested,”​ said Green.

“Further studies are needed to confirm these findings in children and to explore whether oral administration of antioxidants could someday be considered as an effective treatment.”​

In discussing the significance of their findings the researchers believed the improvement seen in the mice was consistent with the hypothesis that antioxidant supplements reduced oxidative stress and hair cell loss.

Previous studies demonstrated that systemically administered ACEMg reduced intense noise-​​ and aminoglycoside-induced​​ free radical formation in the supporting cells and hair cells.

The researchers hypothesised that the detrimental effects of the ACEMg supplement in the inner ears of DIAPH3 mice reflected an increased overexpression of the DIAPH3 protein that resulted in hearing loss.

Source: Nature, Scientific Reports​

Published, DOI: 10.1038/srep22690

“ACEMg Diet Supplement Modifies Progression of Hereditary Deafness.”​

Authors: Kari L. Green, Donald L. Swiderski, Diane M. Prieskorn, Susan J. DeRemer, Lisa A. Beyer,

Josef M. Miller, Glenn E. Green & Yehoash Raphael