Usher Syndrome is a rare hereditary disease. Children suffering from Usher Syndrome are born deaf or hard of hearing and they will also develop a visual impairment from their teenage years. This starts with night-blindness and an ever narrowing field of vision, like looking through a straw. Usher Syndrome eventually leads to deafblindness. Sometimes imbalance problems are also involved. The diagnosis has a great impact on the perspective. There is no treatment yet, but there are promising developments worldwide.
Developments in scientific research
At this moment, an increasing number of centres around the world are busy developing a treatment for the various types of Usher Syndrome (Usher 1b, 1c, 2a, 2d and 3) aimed at inhibiting or stopping the deterioration of vision and hearing. The Radboudumc particularly puts the emphasis on this kind of research on Usher Syndrome type 2a, the most common type of Usher Syndrome that is caused by mutations in the USH2A gene. This gene contains the code for the usherin protein, which plays an important role in the eye and the ear. One of the (gene) therapeutic studies that is conducted is the exon-skipping method. Here one of the coding exons (informative parts of the gene) is removed from the gene and ‘covered’ by a so-called ‘genetic patch’. This results in a shorter but possibly also more functional usherin protein in the retina, by which the deterioration of the eyesight will be stopped or slowed down. Recently, the pharmaceutical company ProQR announced that it will start the first phase 1/2 trials for mutations in the exon 13 at the end of the year 2018. . See ‘ProQR will be start with first trials Ushersyndrome 2a’
In order to be able to test the effectiveness of this type of medicine in clinical trials, it is important to have a clear picture of the natural development of the disease.
However, the exon-skipping method is not suitable for all types of Usher Syndrome and it will take a lot more research to find solutions for all Usher patients. Still, the first important breakthroughs in research are made now!
Ronald Pennings, ENT specialist at Radboudumc Nijmegen (the Netherlands):
“The eventual goal of the Expertise Centre for Usher Syndrome is to be globally leading in the development of (gene) therapy for Usher Syndrome.”
Usher Syndrome Expertise Centre
Dr. Ronald Pennings is recently received the prestigious title ‘Principal Clinician’. With this he wants to set up a trial centre for medicinal treatment of patients with hereditary loss of hearing, including Usher Syndrome, within Radboudumc. Prof. Carel Hoyng is as ophthalmologist of the Radboudumc also directly involved in the care for and research into Usher Syndrome. Additionally, he leads the trial centre of the Ophthalmology department, which is studying retina degeneration by means of testing new medicines. Hoyng and Pennings together lead the Expertise Centre for Usher Syndrome. “The eventual goal of the Expertise Centre for Usher Syndrome is to be globally leading in the development of (gene) therapy for Usher Syndrome. Not only the developments in the laboratory of Erwin van Wijk, but also detailed examination of the natural development of Usher Syndrome with as many people as possible will enable us to obtain this position”, according to Ronald Pennings.
CRUSH study and a CRUSH database
The CRUSH study will map out and analyse the natural development of the progressive disease Usher Syndrome with 50 patients for a period of five years.
The protocol of this study is in line with the first international natural development study, the RUSH2A study of Prof. Duncan in California, with makes exchange of data possible.
Apart from the CRUSH study, an (international) accessible CRUSH database will be set up in the Radboudumc as well for properly recording the results of the examinations.
The CRUSH database is a collection of various clinical data, including audiograms, field of vision examinations and DNA results. In this way the prognosis can be better recorded and a possible explanation for the large individual differences in loss of hearing and eyesight between patients, even of the same family, can be found. This CRUSH database will be accessible for other centres, so they can store their data in the database as well.
Most patients are already known in the national RD5000 database, but this database only contains personal data and the diagnosis. The Radboudumc works together with the physicians and researchers working with the RD5000 database. The CRUSH database, in which the clinical data of patients are stored as well, is intended for all people who have been diagnosed with Usher Syndrome. Researchers of the CRUSH study will select patients from the CRUSH database who meet the criteria and then invite them to participate in the CRUSH study. You can register for the CRUSH database by sending an e-mail to firstname.lastname@example.org
Stichting Ushersyndroom, Ronald Pennings (ENT specialist) and Carel Hoyng (ophthalmologist) of the Radboudumc advise all patients suffering from Usher Syndrome to compose their own files, making sure that the data will quickly be known when registering for the CRUSH database. See ‘Start setting up your own patient file!’
Annouk van Nunen, secretary of Stichting Ushersyndroom and patient herself is happy with the start of the CRUSH study and the CRUSH database. “At this moment there are many families within which several children are affected by Usher Syndrome. However, even between brothers and sisters there are major individual differences in the level of deterioration of eyesight or hearing. If it is known which external factors may influence the deterioration of eyesight and hearing, patients can timely anticipate and make a contribution to slowing down the deterioration themselves. Everyone participating in the CRUSH database makes a contribution to finding the solution. As soon as the CRUSH study has been started, the focus will be shifted towards the acquisition of more funding, so as to make it possible to follow more patients suffering from other types of Usher Syndrome in detail in the future in a study. All patients (young and old, type 1, 2 or 3) play crucial roles in the eventual unraveling of Usher Syndrome.”
In short, the CRUSH study and the CRUSH database are in the interest of all people diagnosed with Usher Syndrome. This is the only way to unravel the disease more quickly and to substantially shorten future trials in the Netherlands or elsewhere in the world.
The full financing of the CRUSH study is guaranteed by Stichting Ushersyndroom for a period of five years, also thanks to the donors and the co-financing of the Dutch Dr. Vaillantfonds and Oogfonds. #CRUSH4all