GENE THERAPY FOR USH2D
Mutations in the whirlin gene lead to Usher syndrome type 2d (USH2d is rare) or non-syndromic hearing loss (DFNB31) in humans. In a study by the Wade Chien group (NIDCD, Bethesda, USA) a healthy copy of the whirlin gene was delivered via an AAV vector to the inner ear of newborn mouse models in which the whirlin gene was switched off. Addition of this new whirlin gene copy to the inner ear of neonatal mice (within 5 days after birth) resulted in an improvement in balance and hearing for at least 4 months (the treated mice were no longer followed in this study).
This study shows that gene therapy could be a possible treatment option for hereditary balance and hearing disorders. However, it is important to realize that there are significant differences between the development of human and mouse inner ears. For example, the human inner ear is fully developed and functional at birth, while the mouse’s hearing organ is only functional a few weeks after birth (from 20 days). Most of the published studies showing recovery of hearing function in mouse models after treatment with a form of genetic therapy are based on treatment of neonatal mice (<5 days after birth). However, the positive effect of these treatments is no longer observed if the administration takes place from 14 days after the birth of the mouse. In concrete terms, this means that in humans the treatment should take place on the unborn child (= in utero) in order to be effective. This results in both practical and medical-ethical objections and will therefore not be applied in patients for the time being. In addition, there are no indications (yet) that USH2d or DFNB31 patients have balance problems, in contrast to the published whirlin mouse models. Additional studies are therefore necessary to provide a detailed overview of the function of the equilibrium organ in patients with whirlin mutations. Future research by this group will show whether this form of therapy could possibly be successfully applied to treat whirlin-related retinitis pigmentosa.