Currently, there is no cure for Usher syndrome and no way to halt the retinal degeneration or to restore normal cochlear function. This is why the early diagnosis is critical for best management of the disease. The earlier the parents know that their child has Usher syndrome, the sooner special educational training programs to manage the hearing and vision loss can begin. Management typically includes hearing aids, auditory training, assistive listening devices, cochlear implants, or other communication methods such as sign language and Braille instruction. Low-vision services, orientation and mobility training, and independent-living training should be offered.

General recommendations

Hearing: Hearing aids are usually ineffective in individuals with USH1 (due to the severity of the hearing impairment), but are helpful in the other types of the disease. Cochlear implantation should be seriously considered, especially for young children. It consists of surgical implantation under the skin behind the ear of a complex electronic device that works as an artificial cochlea. With the use of a highly sensitive speech processor, it can send the sound from the ear to the brain and provide a sense of interpretable sound to individuals with severely impaired hearing. Most often, a single cochlear implant is sufficient to acquire spoken language. The bilateral implantation may improve hearing in noisy rooms and help localization of sound. However, there are still no definitive studies on the benefits of bilateral versus single cochlear implant. Cochlear implantation may also be warranted in older individuals with USH2. Communication skills should be optimized by receiving specialized training from educators of hearing loss and speech training to normalize language.

Vision: Management of progressive sight loss in Usher syndrome should follow the recommendation for management of retinitis pigmentosa.

Balance: Tunnel vision and night blindness, together with vestibular areflexia, can seriously increase the likelihood of accidental injury. Bike riding or ice skating can be dangerous for children with Usher syndrome. At the same time, well-supervised sports may help them to compensate by becoming more adept at using the somatosensory component of the balance system.

Educational programs should begin as soon as possible. They should be tailored depending on the severity of the hearing and vision impairments on the one hand and, on the other hand, on the age and abilities of the individual. Access to low vision services and community support, as well as career counseling may be very helpful.

Therapies under investigation

Gene therapy to replace defective Usher genes is a potential approach to prevent blindness in Usher syndrome. The gene therapy may also be used to treat hearing loss. Retinal degeneration in Usher syndrome seems suitable for treatment by gene therapy because of the monogenic recessive inheritance in most cases. In addition, because of the associated impaired hearing at birth, Usher syndrome patients can be more readily identified prior to the onset of retinal degeneration. At present, real progress with gene therapy for Usher 1B has been achieved. On 20 January 2010, Oxford BioMedica, a U.K. partner of the Foundation Fighting Blindness, has received orphan drug designation from the Committee for Orphan Medicinal Products of the European Medicines Agency (EMEA) for Usher syndrome gene therapy known as UshStat (a gene-based therapy for the treatment of USH1B). UshStat is designed to deliver a corrected version of the MYO7A gene into the retinal cells using the LentiVector® gene delivery technology. Clinical development (Phase I/II) is expected to start in 2011. The adeno-associated virus (AAV)-mediated whirlin replacement as a treatment option is currently under evaluation.

In clinical trials of a gene therapy for Leber congenital amaurosis (a severe retinal degeneration condition) some vision was restored in young adults who were nearly blind. The success with this treatment raises real hopes for development of gene therapies for retinal degenerative diseases, including Usher syndrome.

Encapsulated cell technology (ECT) for delivery to the retina of a therapeutic agent (NT-501) that preserves vision is currently under testing in Phase II/III of human clinical trials (multi-centered, randomized, double-masked, sham-controlled dose ranging studies designed to evaluate the safety and efficacy of NT-501 in patients with retinitis pigmentosa), and the reports from the phase I study were highly encouraging. NT-501 is an intraocular implant that consists of encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF), a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration.

Similarly to cochlear implants that can restore hearing to some deaf people, retinal implants have been designed and, at present, are under evaluation in preclinical and clinical studies. The implant works with a small camera mounted on glasses that sends a signal to the electrode array implanted on the retina. By electrical stimulation of the nerve cells that normally carry visual signal from the retina to the brain, the retinal prosthesis “takes” the function of lost retinal cells and helps to regain a useful level of vision. This therapeutic approach can be implemented in pathologies leading to severely impaired vision such as retinitis pigmentosa or age-related macular degeneration. An artificial retina, a “second sight” device, is currently under investigation in clinical trials. Versions with 16 and 60 electrodes, Argus I and II respectively, are tested and development of the next generation with a higher electrode count is underway.

Potential future therapies

Retinal cell transplantation to replace the degenerating retinal cells and stem cells to create new retinal cells are areas of growing interest and intensive research.