CRUSH: The natural history study
An interim report
The CRUSH study is a study done at the Radboud UMC into the natural development of progression with Usher Syndrome type 2a and USH2A-associated, non-syndromic retinitis pigmentosa (nsRP). CRUSH stands for Characterizing Rate of progression in USHer syndrome. This study is financed by Stichting Ushersyndroom and the co-financing of the Dutch Dr. Vaillantfonds and the Oogfonds.
Usher Syndrome and non-syndromic retinitis pigmentosa (nsRP)
With Usher Syndrome changes in the DNA (the hereditary material) affect the functioning of the cells in the ear and the retina of the eye, which leads to hardness of hearing and possibly balance problems and, additionally, deterioration of the eyesight in the course of time (retinitis pigmentosa). There are three types of Usher Syndrome of which Usher Syndrome type 2 is the most common type with over 50% of the cases. About 80% of the cases of Usher Syndrome type 2 involves type 2a, which is caused by mutations in the USH2A gene. Patients suffering from USH2A nsRP have the same kind of changes in the DNA, but they are not or less hard of hearing.
This study examines the deterioration of the eyesight, balance and hearing of 40 patients suffering from Usher Syndrome type 2a and USH2A-associated nsRP. In view of the major individual differences in the level of deterioration of hearing and eyesight between people suffering from Usher Syndrome, we hope that the results of this study will provide more insight into the development of these disorders. Although there is no treatment yet at this moment, the results of this study will be indispensable for determining the effect of future treatments.
Current state of affairs
The participants of the CRUSH study are annually tested. In a four-year period they are subjected to tests concerning hearing, eyesight and balance by means of various questionnaires. Because of COVID-19, we have had some trouble scheduling the second visits with respect to the study. By now, all measurements of the first two years have been done and, despite COVID 19, we are steadily proceeding towards the end.
Various people are involved in the study and we are pleased to introduce them to you:
Dr Ronald Pennings, ENT specialist and head researcher
“My name is Ronald Pennings and as head researcher I am responsible for the CRUSH study, which means that I coordinate this study. This includes determining which people are subjected to which studies, adjusting protocols when a pandemic comes along, keeping an eye on finances, maintaining contact with the Usher Syndrome Foundation about the progress of the study and a lot of other things. The CRUSH study is really important, as with this study we can collect a lot more details about the deterioration of eyesight and hearing with people having mutations in the USH2A gene. These types of studies are essential for the preparation of future gene therapies. In short, with this study we are working together towards a treatment for Usher Syndrome.”
Dr Erwin van Wijk, head researcher
“My name is Erwin van Wijk. As co-project leader I am involved in the set-up of the study and in selecting the participating patients who based on their genetic diagnose match well with the present developments in the area of gene therapies within my research group.”
Prof Dr Carel Hoyng: ophthalmologist and head researcher
“My name is Carel Hoyng, I am professor in ophthalmology and head of the Clinical Research Centre Ophthalmology. I am the head researcher of the ophthalmology part of the CRUSH study. I know most of the participants in the CRUSH study from my consultations. Unfortunately, I cannot often have a talk with the participants during their visits in connection with the study, but I know that Jack Weeda and the other researchers will take very good care of them. We surely have consultations about the participants on a regular basis.
The CRUSH study is a very important study for us, particularly in view of future treatments and other developments. We expect that the next few years will be exciting years for ophthalmology and people suffering from hereditary retina disorders.”
Dr Cris Lanting, clinical physicist and audiologist
“My name is Cris Lanting and I am involved in the CRUSH study as a clinical physicist and audiologist. It is my job to support and supervise the audiological measurements and data analyses with respect to the various audio-vestibular results. Apart from this, I can give advice about the personal outcomes and revalidation options.”
Jack Weeda, research optometrist
“My name is Jack Weeda and I started working at the Radboud UMC in the year 2006. I have worked as a research optometrist at the Clinical Research Centre Ophthalmology of professor Hoyng since the year 2012. In connection with the CRUSH study, all participants come to me for their screenings and follow-up visits. I examine the participants, for instance to determine their visual acuity and fields of vision and to make photos. Some participants recently came here for their third visits already and we start to know each other a bit. For me this is one of the nice aspects of this work, as contacts are more superficial at the clinic.
I hope that the results of the CRUSH study will make a contribution to gaining even more insight into Usher Syndrome and, of course, that we will soon be able to use them in treatment studies.”
Addy Loeffen-van Dijk, nurse
“Hi, my name is Addy Loeffen. I have worked at the ENT clinic as a nurse since May 2019. I temporarily take over the job of Lieke Knorth. This makes me responsible for various administrative tasks, but I also have direct contacts with our participants. I really like being able to add my share to this study.”
Patricia Gerrits-van Haren, secretary
“My name is Patricia Gerrits van Haren, secretary patient care ENT. I have taken over the scheduling of the CRUSH study since mid-January of this year. I make sure that patients are invited and that all people involved are informed about this. In order to make this schedule run smoothly, I am in close contact with Jack Weeda, Addy Loeffen and Sybren Robijn.”
Sybren Robijn, research physician ENT
“My name is Sybren Robijn and I have as a doctoral candidate of Dr Pennings been involved in the CRUSH study since 2018. I have several tasks within the study. For example, I am responsible for various administrative matters, but I also often have direct contacts with our participants. In the course of the year, I will in full confidence pass on my tasks to my colleague Hedwig Velde. The thing that I will remember most from this study is the privilege of being given the chance to work with such highly motivated and zealous patients.”
Hedwig Velde, research physician ENT
“My name is Hedwig Velde and I recently started as a doctoral candidate of Dr Pennings. I will take over the tasks of Sybren Robijn within the CRUSH study. I am looking forward to making a contribution to this link in the process towards a treatment for this patients group.”