Report CRUSH study

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.

CRUSH study
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.

People involved
Various people are involved in the study and we are pleased to introduce them to you: 

Dr. Ronald Pennings met een zwarte bril, een lach en hij draagt zijn witte doktersjas

Dr. Ronald Pennings

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.”

Erwin van Wijk in zijn lab en kijkt recht in de camera met een lach

Dr. Erwin van Wyk

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.”

Carel Hoyng kijkt serieus in de camera, hij draagt overhemd, colbert met een stropdas

Prof. dr. Carel Hoyng

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.”

Chris Lanting, kijkt met een open blik in de camera

Dr. Cris Lanting

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, draagt een bril en witte doktersjas

Jack Weeda

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.”

Een vrolijk kijkende vrouw staat voor een muur met een kunstwerk en draagt haar verplegersjas

Addy Loeffen-van Dijk

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.”

Een vrouw met blonde bos haren kijkt je recht aan in de camera

Patricia Gerrits-van Haren

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.”

Een hele vrolijke blik van Sybren Robijn

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.”

Een vrolijke Hedwig Velde met haar in de staart en ze draagt een witte jas

Hedwig Velde

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.”

Read also:
Patient and physician jointly take the first step towards treatment of deafblindness
CRUSH study and database for unraveling Usher Syndrome

The RUSH2a and the CRUSH studies

 

Development of gene therapy for large USH2C gene

Patient and researcher form a tandem in scientific research into Usher Syndrome

From left to right: Annouk van Nunen, Rick Brouwer, Deborah Heffernan, Erik de Vrieze, Erwin van Wijk, Ronald Pennings, Carol Brill, Renske Schellens, Ivonne Bressers, Sanne Broekman, Jantine van de Watering.

Usher Syndrome patients and researchers of Radboudumc set the tandem in motion again for scientific research into a treatment for Usher Syndrome, this time concerning type 2C. After the successful USH2A Minigenes study, the results of which will be known early in the year 2020 there will be a follow-up. Stichting Ushersyndroom (Dutch Usher Syndrome Foundation) finances, with a contribution from CUREUsher from the UK/Ireland and the Landelijke Stichting voor Blinden en Slechtzienden (LSBS), the new study into Minigenes for USH2C. In order to celebrate this milestone, five researchers of the national Usher Syndrome Expertise Centre of the Radboudumc involved surprised the same number of patients with a ride on the tandem. 

In their white coats head researcher Erwin van Wijk, Erik de Vrieze and ENT specialist Ronald Pennings cycled in a good humour as co-pilots to the agreed place. Only Ivonne Bressers, chairwoman of Stichting Ushersyndroom (Usher Syndrome Foundation) was involved in the plot. Like a string another two half-empty tandems followed with 2 young researchers who are daily engaged in doing research into a treatment for Usher Syndrome, a disorder which slowly makes 400,000 patients around the world both deaf and blind.

With rare diseases like this, the contact between physicians, researchers and patients is crucial. Patients, parents and relatives are the drive force behind the scientific research into a treatment by collecting donations, acquiring resources and close consultation with physicians and researchers. This interaction brings a treatment for progressive deafblindness closer at a faster pace.

“We are unmistakably united as a duo on a tandem; the researcher as co-pilot, the patient as firer.”
Erwin van Wijk, head researcher in the Radboudumc

“The input and knowledge that patients bring up themselves is not only highly inspiring for me and my colleagues, these also put us on new tracks in unravelling Usher Syndrome. We are unmistakably united as a duo on a tandem; the researcher as co-pilot, the patient as firer,” the head researcher of Radboudumc Erwin van Wijk tells us.

Five Usher patients are sitting at a table in a café drinking coffee; some with their backs to the window. Patient Rick Brouwer gets up surprised when Erwin van Wijk appears within his tunnel vision. Rick is one of the people for whom the Minigenes USH2C study gives hope. He has been involved as from the foundation of Stichting Ushersyndroom (Usher Syndrome Foundation) and suffers from Usher Syndrome type 2C himself.
“Today really is an important day! Thanks to the positive results of the Minigenes USH2A study a step is made to USH2C. There soon will be a treatment for all people suffering from Usher!”, Rick calls out deliriously happy.

“For the first time in my life I really have hope that there will be a treatment for all Usher patients all over the world!”
Carol Brill, Usher patient and member of the Board of CUREUsher

Carol Brill of CUREUsher from Ireland is there as well and starts laughing when the researchers seduce them to take a ride on the tandem after having expressed their thanks for their cooperation. Carol: “What a great experience to cycle together through the city! I will come over to live here! For the first time in my life I really have hope that there will be a treatment for all Usher patients all over the world!”

Promising preliminary investigation
In the year 2016, Stichting Ushersyndroom (Usher Syndrome Foundation) made a financial contribution to the study into the functioning of USH2A Minigenes as a future treatment method. Usher Syndrome is a rare genetic disease in which faults (= mutations) in about ten different genes lead to a progressive form of deafblindness. The large size of the genes in which the most causal mutations are found with most patients makes classic gene therapy impossible. This is because these mutated genes are simply too big to be packed in the available viral vectors that are required for delivering the gene at the correct place in the retina. This is an ultimate challenge for the researchers. A creative solution is needed to still process the gene in a viral vector.

Erwin van Wijk expects to be able to publish the first study results of the USH2A Minigenes study early in the year 2020. Van Wijk will now start a similar study for USH2C, titled ’Pre-clinical development of a minigene augmentation therapy for the future treatment of USH2C-associated retinitis pigmentosa’. Never before a research institute has had the courage to start developing a gene therapy for this huge USH2C gene. Stichting Ushersyndroom (Usher Syndrome Foundation) will subsidise this 4-year study of Erwin van Wijk (and Erik de Vrieze and Ronald Pennings) with € 250,000 with co-financing from CUREUsher and L.S.B.S.

In order to celebrate this milestone, five researchers of the national Usher Syndrome Expertise Centre of the Radboudumc involved surprised the same number of patients with a ride on the tandem. 

The Medical Advisory Council of Stichting Ushersyndroom (Usher Syndrome Foundation) is very positive about this study because of the highly promising preliminary investigation with the USH2A Minigenes, which has demonstrated that it is possible to make minigenes and that these work in the correct/expected way.

According to the members of the Medical Advisory Council, the applicants have the appropriate knowledge, expertise and material at their disposal to carry out the proposed experiments for the USH2C gene (ADGRV1). As far as the members of the Medical Advisory Council know, no study is presently done into USH2C, while this is the third most common form of Usher Syndrome which about 40,000 people around the globe are suffering from.
Cindy Boer (member of the Medical Advisory Council, doctoral candidate internal medicine, faculty of human genomics, ErasmusMC and suffering from Usher Syndrome herself): “In consultation with Erwin van Wijk and Erik de Vrieze the Medical Advisory Council has made an addition to this study proposal. We would like to apply this to humans by making use of human skin cells. In this way we can investigate whether the minigenes behave well in human cells and whether the proteins properly unfold. This may sometimes be different in human models as it is in animal models and therefore it gives a good indication about the functioning of the gene therapy for humans.”
The USH2C Minigenes study is completely in line with the objective of Stichting Ushersyndroom (Usher Syndrome Foundation): “There will be a treatment for Usher Syndrome in 2025!”

The tandems with patients and researchers will continue their journeys; these will be bumpy, but their confidence in the process will drive them and this will bring a treatment for Usher Syndrome closer than ever before. Difficult ways will lead to great destinations. 

The CRUSH study as a preparation for future trials
Earlier this year, Stichting Ushersyndroom (Usher Syndrome Foundation) also financed the CRUSH study of the Radboudumc with co-financing from the Oogfonds and the Dr. Vaillantfonds, a study in which researchers will map out the natural development of Usher Syndrome in great detail. Researchers really intensively follow the Usher Syndrome patients. Expectations are that during a research period of five years more knowledge will have been gained about the development of the deafblindness related to various types of Usher Syndrome.
In case of a positive result of the new study into Minigenes for USH2C the research team will be well prepared for any next phase 1 / 2 clinical trial.

Text: Maartje de Kok
Photo and video: Richard Brusse

Read also:

CRUSH study and database for unraveling Usher Syndrome

Stichting Ushersyndroom will finance the start of the CRUSH study, a natural development study into Usher Syndrome. With this the basis can be laid for future trials. Patients can, with their own files at hand, register for the CRUSH database and so bear the responsibility for the solution and the unraveling of the disease that leads to deafblindness themselves. The CRUSH study fits in with the mission of Stichting Ushersyndroom: ‘A treatment for Usher Syndrome in 2025!’

Usher Syndrome
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
Join the CRUSH databaseAt 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 ushersyndroom@radboudumc.nl

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!’

‘CRUSH USH’
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

Read Press Release ‘Patient and physician jointly take the first step towards treatment of deafblindness’

Patient and physician jointly take the first step towards treatment of deafblindness

Stichting Ushersyndroom finances CRUSH study

The expertise centre for Usher Syndrome in Radboudumc in Nijmegen (the Netherlands) will start a natural development study into Usher Syndrome. This is a very important step in the research into a treatment of Usher Syndrome, because this study may substantially shorten the running time for trials. Ophthalmologists and ENT specialists will together conduct this CRUSH study. Stichting Ushersyndroom will finance this five-year study with over €257,000,–, made possible by the donations and the co-financing of the Dutch Dr. Vaillantfonds and the Oogfonds.

The CRUSH study (Characterizing Rate of progression USHersyndrome) is a cooperation between the Usher Syndrome Foundation, ophthalmologists, ENT specialists and the researchers of the Radboudumc. This study will map out and analyse the natural development of the progressive disease Usher Syndrome with 50 patients for a period of five years. Children suffering from Usher Syndrome are born deaf or hard of hearing and from their teenage years their eyesight will deteriorate as well. This starts with night-blindness and an ever narrowing field of vision, which is like looking through a straw. Usher Syndrome is the most common type of deafblindness.
By starting now to properly register of the natural development researchers can determine how many people are required, what studies are to be conducted when and how long a trial must take in order to be able to unambiguously and exactly register the effect of a treatment compared with the natural development.

CRUSH study as a track-record for other eye diseases
By starting natural development studies with 50 patients suffering from Usher Syndrome a track-record is built up which can be extended in the future. By mapping out the deterioration of vision and hearing, the basis is laid for the future evaluation of the effectiveness of clinical trials related to Usher Syndrome. These experiences are not only important to patients suffering from Usher Syndrome, but to patients with other hereditary eye disorders as well. This study can be an example of how the running time can best be shortened to make sure that studies into effectiveness can be started in time.

A. van Nunen, secretary of Stichting Ushersyndroom and patient herself:

“The CRUSH study can help ophthalmologists and ENT specialists to inform patients better about the prognosis and the development of the deterioration of their eyesight and hearing, thus enabling people suffering from Usher Syndrome to better arrange their lives.”

Usher patients hope that this study will also provide an explanation of the individual differences within families and to find and answer to the question which external factors have influence on the development of the disease. For this reason a CRUSH database will be set up apart from the CRUSH study. Annouk van Nunen: ‘Knowledge about the natural development for each mutation improves the early diagnosis and guidance of young parents and the care for people suffering from Usher Syndrome. The CRUSH study can help ophthalmologists and ENT specialists to inform patients better about the prognosis and the development of the deterioration of their eyesight and hearing, thus enabling people suffering from Usher Syndrome to better arrange their lives.’
Do you want to know more about the CRUSH study and the CRUSH database?

Read more:
CRUSH study and database for unraveling Usher Syndrome
The RUSH2a and the CRUSH studies
Report CRUSH study
Know your gene!

Stichting Ushersyndroom finances restart of ‘minigenes’

Stichting Ushersyndroom makes available an amount of €35,000 to Radboud UMC for the restart of the ‘minigenes’ study in connection with Usher Syndrome. This involves the study which gives hope to all people with mutations in the USH2A gene.

Usher Syndrome is a rare hereditary disorder. The children suffering from this disorder are born deaf or hard of hearing and apart from night-blindness they also experience a progressive loss of eyesight. Eventually, people suffering from Usher Syndrome become both deaf and blind. Usher Syndrome is the most common type of hereditary deaf-blindness. There is no treatment yet that can stop the deterioration of both hearing and eyesight, but there is hope.

Large gene
Although more than half of all people suffering from Usher Syndrome have mutations in the USH2A gene, this gene is not a target in the current studies into the development of gene replacement therapy. This is because of the size of the protein coding sequence of the USH2A gene (>15,000 bases!). A DNA fragment of such a length does simply not fit into the currently used gene therapeutic vectors (harmless viruses used for packaging genetic material and delivering this at its destination).

Minigenes: the solution for the problem?
In the ‘minigenes’ project, the USH2A gene is artificially made smaller by taking specific parts of the gene and sticking these together (= minigene). This makes it possible to insert these minigenes into the current vectors for use in genetic therapy.
In this project the therapeutic effect of shortened USH2A protein variants will be tested in the zebrafish model. If this is successful, this project may lead to a pre-clinical treatment method for USH2A-related retina degeneration, with which the deterioration of the eyesight could be stopped (within 5 to 10 years). This will have a tremendously positive impact on the quality of life of individual patients. The treatment can be applied to all people suffering from Usher Syndrome.

Stichting Ushersyndroom wants to finance scientific research that offers hope to all people suffering from Usher Syndrome and give a positive impulse to the ‘minigene’ research with an amount of €35,000. The remaining amount was supplemented by ENT Radboudumc. This is guaranteed and so ensures completion of the first phase of this study.

“Minigenes study;
hope for all people
suffering from Usher Syndrome”

Time-consuming and specific
In the Radboudumc, researchers are also conducting other studies that may offer solutions for smaller groups of people with specific mutations in the USH2A gene. However, this study, which tests the therapeutic potential of exon skipping, is a very time-consuming study as a specific treatment is to be developed for each mutated exon. All the more because over 500 different mutations have been identified in the USH2A and these are spread over the entire gene. Even when the developments in the ‘exon skipping’ study show positive progress, this method still does not offer a solution for a significant part of the people with a mutation in the USH2A gene, because the build-up of the gene and protein are not suitable for this.
Recently, a joint venture was entered into with a pharmaceutical company for further development of this exon skipping method into a possible first trial in a few years.
SWODB also made a donation for financing a part of the ‘exon skipping’ study

Start-up Usher Syndrome database
In view of all developments concerning the research into Usher Syndrome it is really necessary to start the ‘Usher Database’ project. First of all, the Usher database is an essential collection of personal data, genetic data and extensive clinical data obtained by conducting a broad set of eyesight and hearing studies. The results of the most recent studies help to make an overview of the natural deterioration of eyesight and hearing of all people suffering from Usher Syndrome. These data will form the basis for future trials during which gene-therapeutic interventions can be tested and compared with this natural deterioration. Secondly, by studying these data an explanation can be found for the huge variation that is found in the clinical picture (even within families sharing the same genetic background).

Therefore the Usher database goes much beyond the national RD5000 database, in which at this moment only genetic and personal data of patients with hereditary retina degeneration are stored.
Usher Syndrome Foundation will concentrate on acquiring funds for the start-up of this project. Without this study and the Usher database the trials of gene-replacement therapies, which may be developed in a couple of years, cannot start either.

Read also:
Minigenes USH2a: What is the status of this investigation?