GENE THERAPY FOR USH 3A – INNER EAR
Dr Kumar Alagramam of the University Hospital in Cleveland (Ohio, USA) is doing research into gene therapy for Usher Syndrome 3A. Initially, the study of Dr Alagramam is focused on the development of a treatment of the progressive loss of hearing with people suffering from Usher Syndrome type 3A. He expects that this type of therapy can also be applied to the eye in order to inhibit the degeneration of the retina.
Just like Dr Dinculescu, Dr Alagramam makes use of a mouse model with mutations in the USH3A gene in his study. He has demonstrated that these USH3A mice suffer from progressive loss of hearing.
This is the first time that this USH3A-related loss of hearing can be copied in mice models. This makes research into a treatment of USH3A-related loss of hearing possible.
Dr Alagramam administrated healthy copies of the USH3A gene to the USH3A mice at two different ages.
The first administration took place during the embryonic development. For this Dr Alagramam modified the genetic material of the mice with the result that certain cells of the inner ear produced the clarin-1 protein even from the embryonic development.
In order to reproduce the effect of the treatment at a later age, Dr Alagramam used adeno-associated viruses (AAVs) to insert healthy copies of the USH3A gene into the inner ears of mice of 1 month old. The mice already suffered from loss of hearing at that moment.
The first study results are cautiously positive. The administration of the healthy copies of the USH3A gene during the embryonic development slowed down the deterioration of the loss of hearing.
The administration of the healthy USH3A gene in young mice suffering from loss of hearing could not improve the hearing function or inhibit further deterioration of their hearing.
From these results, Dr Alagramam concluded that a gene therapy for loss of hearing with patients with mutations in the USH3A gene is to be administered before the loss of hearing is developed. With people suffering from Usher Syndrome type 3A the loss of hearing is congenital or it is developed at a young age. This makes the further development of this therapy more difficult, as it is presently not possible to test the gene therapy with people of a very young age.
GENE HERAPY FOR USH 3A – RETINA
Unlike many other genes related to Usher Syndrome, the USH3A gene is relatively small. A research group of the University of Florida (USA), led by Dr Astra Dinculescu, is working on the development of gene therapy for the retina in Usher Syndrome type 3A patients. In their research, Dr Dinculescu and her colleagues make use of mouse models with mutations in the USH3A gene. These mice do no longer produce the clarin-1 protein. Just like with people, mutations in the USH3A gene lead with mice to deterioration of the eyesight.
The researchers used adeno-associated viruses (AAV’s) to insert healthy copies of the USH3A gene into the rods and the cones of the retina of the USH3A mouse. Through this method the researchers succeeded in recovering the production of the clarin-1 protein in the retina. The treatment also improved the functioning of the retina with the USH3A mouse and inhibited the deterioration of the retina.
At this moment, the research group is working hard on improving the method of administration of this type of gene therapy for USH3A. For an optimum result it is important that the healthy copies of the USH3A gene end up in as many rods and cones as possible without side effects occurring in the retina.
