Into daily life with an artificial organ of balance

The introduction of the artificial organ of balance has come one step nearer closer again, thanks to a subsidy of over € 700,000 from ZonMw, Health Holland and the Heinsius Houbolt Foundation. With this financial impulse scientists of the Maastricht UMC+ will implant an artificial version of this minuscule organ into eight patients suffering from serious imbalance problems. This is the first time that the daily life with an artificial organ of balance will be simulated in a test environment. The objective is to sooner make the treatment available to patients.

Micro-CT-scan of the human inner ear; yellow: individual nerves; blue: bone and membrane structures (Copyright: Maastricht UMC+)

The organ of balance is located deeply in the so-called petrous bone, behind the ear (one on each side). Here it makes sure that we experience a stable world. People with whom the organ stops functioning on both sides, experience a feeling of disorientation, dizziness and/or discomfort. They continuously lose their balance and this strongly restricts their daily functioning. As much as 75% of the patients is unfit for work. So far, treatment by surgery or medication has been impossible. The artificial organ of balance is meant to change this.

Balance and hearing implant
Another important scientific development is the introduction of the vestibulo-cochlear implant (VCI), a balance and hearing implant in one.
USH type1– there are three different clinical types – includes both congenital deafness and failure of the organ of balance. A part of the people suffering from USH type 3 is confronted with failure of balance in later childhood or at a later age. 
The artificial organ of hearing and balance, the VCI, can improve the lives of these patients.  

Daily use
The artificial organ of balance is a small implant which takes over the work of the ‘real’ organ. First of all, it registers the movements that people make. These signals are then passed on to the brains to determine the orientation and to keep the balance. Since the development of the first prototype in 2012, the physicians of the Maastricht UMC+ and the university hospital of Geneva have given an artificial organ to thirteen patients. At this moment, the implants are only used in test settings. “Now is the time to bring things closer to the patients and to study the daily use”, according to ENT specialist Dr Raymond van de Berg and his colleague Marc van Hoof.

Available in a few years
The artificial organ of balance, called a Vestibular Implant (VI)) is implanted into the ear by surgery. This VI can be inserted beside an already present cochlear implant. The VI can be available to all patients in the Netherlands in about 5 years.

Quality of life
With this subsidy, an artificial model of the organ of balance can be implanted into eight patients with failure of the organ of balance on both sides. For this patients are hospitalised in a rehabilitation setting in which the daily use, the functioning and the safety of the implant are analysed. Additionally, an overview is made of the personal requirements and needs of the patients. Also, it is investigated whether the amount and quality of information sent from the implant to the brains can be further expanded and improved. Van de Berg: ‘Of course, the eventual objective is to literally and figuratively offer the patients more balance and so give them back their quality of life and enable them to better function in society.’ At a rough estimate, Europe counts 500,000 patients suffering from imbalance problems. The introduction of the artificial organ of balance could help hundreds of patients in the Netherlands.

Participation in user committee
A female patient suffering from Usher Syndrome is a member of the user committee of the VertiGO! study. She assists in the further development of the VI and the VCI. This patient does not have the VI/VCI herself.

The study is titled ‘VertiGO!’ and the research is co-funded by Health Holland, the Hoormij Foundation, ‘De negende van’ Foundation, the Usher Syndrome Foundation and external partners, including the University of Geneva, manufacturer MED-EL, the Heinsius Houbolt Foundation, the Apeldoorns Duizeligheidscentrum, LUMC and the Radboud UMC.

Source: Maastricht UMC+

Study of the natural Development for USH1B started

18% of the 400,000 patients suffering from Usher Syndrome around the world has mutations in the USH1 gene. Due to the mutations (changes) in the USH1B gene the myosin protein is not or hardly produced. Due to a shortage of the myosin protein the cochlea in the ear of the unborn child is not properly built up during pregnancy. Consequently, children suffering from USH1B are born deaf and have balance problems. The first signs of reduced eyesight will show during childhood. This starts with night-blindness to be followed by an ever narrowing field of vision. Children born with USH1B are given cochlear implants on two sides in their early childhood, which make them hear well and enable them to properly develop speech and language, if necessary supported by sign language.

For patients suffering from USH1B there is little information available about the natural development of the eyesight. After the start of the RUSH2a and the CRUSH studies in the Radboud UMC in Nijmegen, the Netherlands, a study into the natural development of USH1B was started in the Oogziekenhuis Rotterdam, the Netherlands. The first patients have already been included, but more participants are required. In this study researchers want to follow 15 – 20 participants with 3 eye tests in 2 years.

Read the call of the Oogziekenhuis Rotterdam below.

Usher type 1B: call for participation in the natural development study.

A study into the natural development with patients suffering from the Usher Syndrome type 1B was started in the Oogziekenhuis Rotterdam, the Netherlands. This type of Usher is characterised by serious deadness and balance problems from birth, followed by a development of retinitis pigmentosa (RP) during childhood. The Usher Syndrome type 1B is much more uncommon than, for instance, Usher Syndrome type 2A. Therefore less is known about the seriousness and the progression of this type of retinitis pigmentosa. Usher type 1B is caused by changes (mutations) in the MYO7A gene. This gene determines the code for the myosin protein. The function of myosin is, among others, to take care of transport in the retina cells. Professor Alberto Auricchio of the TIGEM institute in Naples, Italy, has studied gene therapy as a treatment of RP caused by MYO7A mutations for many years. He has received a major grant from the European Union to continue his research (

A part of this large project is the natural development study, in which not Only the University of Naples but the Oogziekenhuis Rotterdam and an institute in Madrid participate as well. The information gained from this study will eventually be very important to be able to compare the effect of gene therapy with ‘doing nothing’.

This study includes 3 extensive eye tests in the Oogziekenhuis Rotterdam: there is a baseline measurement which will be repeated after 1 en 2 years. It is important to mention that no treatment will be tested in this part of the study.

We would like to come in contact with patients who want additional information about the study and who may want to participate. It is important that you carry MYO7A mutations. Another restriction is that children younger than 8 years cannot participate. If you want additional information about this study, you are heartily invited to contract Dr Ingeborgh van den Born of Ms Annemiek Krijnen (tel.: 0031-(0)10 -4023449, e-mail

Do you suffer from Usher Syndrome type 2? Register for the CRUSH study in Nijmegen, the Netherlands. Participants are needed for this study as well! Read more about the CRUSH study and how to register

International cooperation with Irish and UK patients.

Stichting Ushersyndroom have had close ties with Usher patients from Ireland and the UK for some years. Patients with Usher syndrome in Ireland and the UK have no central organisation specifically for those with the disease. CUREUsher was officially established at the beginning of this year. At the end of January, the board members of CUREUsher and the board of Stichting Ushersyndroom visited the Radboudumc to discuss cooperation between the two groups and to exchange information. CUREUsher will host the ‘Jo’s Scafell Pike Challenge’ in early April, with which they will raise money for Stichting Ushersyndroom for the pioneering research of Erwin van Wijk in the Radboudumc in Nijmegen.

Currently, major steps are being taken worldwide in scientific research into treatment for and unravelling Usher Syndrome. International cooperation between patient organizations, researchers and doctors is very important at this time. By working together, we can raise larger grants and funds for scientific research, researchers can share their knowledge and doctors can diagnose and map patients in the right way. International cooperation can also lead to smoother regulations within Europe, so that trials can be started earlier and medicines or treatments become cheaper for all patients.

CUREUsher, a patient-led organisation, was founded by Joanne White in the UK, with co-founders Deborah Heffernan and Carol Brill in Ireland. Their main objective is to raise funds and donations to go towards scientific research into the causes and treatment of Usher Syndrome for all patients worldwide. Joanne, Deborah and Carol hope with the establishment of the organisation it will give a strong message to the government and the care services in their countries to acknowledge deafblindness by Usher Syndrome, so that patients can gain better access to the right care and services.

Jo’s Scafell Pike Challenge
Joanne White, chairperson and founder of CUREUsher: “For the first time I hope for a remedy for Usher Syndrome. With a lot of courage, determination and positivity – I think we all have this power – there is a solution for Usher Syndrome.” Joanne wants to do the ‘Jo’s Scafell Pike Challenge’ together with you. A challenge to climb the highest mountain peak in The Lake District on the weekend from 5 to 7 April 2019 under the guidance of a guide. You can find more information about this challenge by clicking the link below.

Joanne and her ‘Usher friends’ invite as many people as possible to join. All funds raised and sponsoring will be earmarked through Stichting Ushersyndroom and will benefit the promising research by Erwin van Wijk. Also enthusiastic people from the Netherlands are cordially invited to join this challenge in the Lake District!

The RUSH2a and the CRUSH studies

CRUSH has been aligned to RUSH2a
Also thanks to the Medical Advisory Council of the Usher Syndrome Foundation, the content of the CRUSH study has been aligned to RUSH2A. This means that the research questions and the study measurements are largely similar, allowing the results of the CRUSH study to be compared with those of the RUSH2a study. This comparison is of scientific value.
The set-up of the CRUSH study leaves the expertise centre in Radboud UMC some space to make adjustments in the research protocol. In the international RUSH2a study this is highly restricted, as this study is to be conducted in all countries in exactly the same way.
Examples of differences are: the CRUSH study is somewhat more focused on the quality of life (questionnaires). The CRUSH does not apply a smelling test, but the RUSH2a study does. The CRUSH tests for balance, which the RUSH2A does not. The RUSH2A applies genetically stricter inclusion criteria. Some patients are not eligible for RUSH2A whereas they are for CRUSH and vice versa.

A large group of patients
Internationally, both syndromic and non-syndromic Usher patients are eligible for the RUSH2a study. Patient will not participate in both studies.
Patients with non-syndromic retinitis pigmentosa are not eligible for the CRUSH study.
Only patients with a mutation in the 2a gene will participate in the RUSH2a studies. The CRUSH study can include patients with mutations in various gene types. Both studies are equally important from a scientific point of view. One study does not have more advantages or risks than the other.
20 patients can participate in the RUSH2a study and for the CRUSH study 50 patients will be selected and asked to participate. The RUSH2a will be coordinated from the Ophthalmology department department, whereas the ENT department coordinates the CRUSH study.

What about the database?
The CRUSH database is a database specifically set up for patients suffering from Usher Syndrome. Here not only the contact data and genetic results are saved, but those of the field of vision and hearing tests as well. The CRUSH database provides an overview of all patients suffering from Usher Syndrome in a uniform database and this may simplify selection processes for participation in a study and/or trial.
The CRUSH database is managed by the Usher Syndrome Expertise Centre in the Hearing & Genes department of Radboud UMC.
An Usher Syndrome patient who has been registered for the RD5000 database will not automatically been registered for the CRUSH database and vice versa. The ENT specialists and the ophthalmologists in Radboud UMC work closely together, thus ensuring exchange of knowledge within this Academic Centre. You can register for the CRUSH database by sending an e-mail to

Natural development for USH 1B
A study into the natural development with patients suffering from the Usher Syndrome type 1B was started in the Oogziekenhuis Rotterdam, the Netherlands. The information gained from this study will eventually be very important to be able to compare the effect of gene therapy.


If you slowly become become deaf and blind

Ronald Pennings, MD, PhD, ENT consultant and Usher syndrome specialist

Slowly become both deaf and blind. It is hard to imagine. Still, this is reality for people suffering from Usher Syndrome. Usher Syndrome, actually what type of disorder is this? And much more important: is there a treatment for stopping or slowing down the process of becoming both deaf and blind?Ronald Pennings, MD, PhD, ENT consultant and Usher syndrome specialist of the national Usher Syndrome Expert Centre in Radboudumc Nijmegen, the Netherlands, tells about this and answers the most burning questions.

‘Usher Syndrome is a hereditary disorder which affects both hearing and eyesight. In principle, the loss of hearing is always congenital. As opposed to hearing, the eyesight is normal at birth, but this will deteriorate in the course of the years.
There are three different types of Usher Syndrome: types 1, 2 and 3. People suffering from type 1 are born completely deaf and they have a poor balance. This is because the organ of balance – which is connected with the cochlea – does not work. These children will develop their first problems with eyesight at the age of eight or ten. They find it more and more difficult to see in the dark, also called night-blindness. Subsequently – as they get older – their fields of vision narrow down and as a result they will see through a kind of tunnel at a certain moment. The things they can still see will eventually become less sharp. This means that the eyesight gradually deteriorates.’

People suffering from type 2 have a congenital loss of hearing for which hearing aids can be used. These people slowly lose their hearing. The first problems with the eyesight show around puberty, a bit later than with people suffering from Usher type 1. Their eyesight will gradually deteriorate as well. Finally, we also have Usher type 3, which is very rare in the Netherlands. This type is more progressive, so here the loss of hearing as well as the loss of eyesight can go very fast.’

What is the cause of Usher Syndrome? 
‘It is a recessive hereditary disorder. Here both parents carry a fault (mutation) in one of the Usher genes without experiencing any trouble. These genes play a major role in the ears and eyes of people, making sure that we can hear and see well. We have two ‘copies’ of each gene. If one copy has a fault, you are carrier but you will not suffer from Usher, because you also have a normal copy. At the moment that both parents pass on their faulty copies of the gene to their child, the child will suffer from Usher Syndrome. In this case the child does not have a normal copy of this gene left.

The copy in which the fault is present will prevent the gene from properly producing its protein. This protein is important for both hearing and eyesight. If you have another good copy, you will have a normal protein on that side. At the moment that both copies are faulty, you will no longer produce a normal protein. When the proteins are not working well, there will be loss of hearing and deterioration of eyesight.’

How big is the change of developing Usher Syndrome?
‘The syndrome is rare, which makes the chance of a child suffering from Usher very small. A child with normal hearing has virtually no chance of Usher Syndrome. In case of congenital hardness of hearing this chance will be larger, about three to six percent. For each form of congenital loss of hearing it is advised to conduct a genetic test for the cause of this. This test can confirm Usher Syndrome, even if there are no problems with seeing yet. When both parents are carriers of a mutation in the same Usher gene, they have 25 percent chance of getting a child with the syndrome.”

How often does this occur?
‘We do not have any exact numbers, but we think that about 800 people suffer from Usher Syndrome in the Netherlands. So this really is a rare syndrome.’

How do people suffering from Usher Syndrome cope with the knowledge that they will slowly become both deaf and blind?
‘In very different ways and with ups and downs. You sometimes see people being seriously confronted with their impairments, as everything costs more energy. On the other hand, there are also periods in which they really try to make things work and make the most of their lives.
There is a lot of power behind this and that is the nice thing about this group of people. That they are still very active despite their impairments. This shows, for instance, in a foundation that have been set up by patients and their relatives, such as Stichting Ushersyndroom. This are a very active foundation that try to improve the lives of people suffering from Usher.’

Is there a treatment?
‘The deaf children suffering from type 1 can be given a cochlear implant. This is an implantable hearing aid with which we place an implant with an electrode in the cochlea. The implant converts sounds into an electric pulse, which then is passed on to the cochlea. After a rehabilitation process, people will be able to hear with this. This makes sure that these children instead of growing up as deaf children grow up as children with a hearing impairment, but they can go to a regular school. To type 2 applies that both children and adults can be rehabilitated with a hearing aid. Sometimes older people suffering from type 2 need a cochlear implant because of the progress of the loss of hearing.

So there is a lot we can do to improve the hearing with the current state of affairs. With respect to eyesight, however, there still really is a problem. Genetic therapies are being developed at this moment, but for this we need to know what is genetically going on. It is important to investigate this and to make a diagnosis based on this. By now, the first steps towards developing gene therapies for the three types have been taken. We are also working on a future treatment for type 2 in our laboratory. However, it will still take many years for a treatment to become available. For the time being, the objective of this study is to slow down or even stop the deterioration of the eyesight in particular.

At this moment, we do not expect that we will be able to give someone who has become blind his or her eyesight again. However, if we indeed manage to slow down or even stop the deterioration process, we have really achieved a lot for the younger patients. This is all still in the future. The first clinical trials have started and we have to wait for the results of these and whether they will lead to medicines for this group of people.’

What can people do themselves?
‘There are indications that exposure to intense (sun)light – also on cloudy days on which the light is intense – it is useful to wear a hat and sunglasses. This could partly protect against increasing damage of the retina. Another important thing is: people suffering from Usher should be careful with their ears, for instance at festivals, clubs or loud music. In these situations they’d better take off their hearing aids or not stand very close to the loudspeakers, although most people suffering from Usher Syndrome will sufficiently take this into account by themselves.’

Dr. Ronald Pennings is ENT specialist and otologist at Radboudumc in Nijmegen, the Netherlands. The Radboud University Medical Centre is an academic hospital and cooperates with the Radboud University of Nijmegen.

Source: Gezondheidsnet [Health net] and

Do you have the diagnosis Usher syndrome and you want to know more?


The Usher Syndrome knowledge portal has been developed by and for people suffering from Usher Syndrome with the support of their social environments, physicians and scientists.. Stichting Ushersyndroom [The Usher Syndrome Foundation] makes this portal available and hopes that this will fulfil a need for information and knowledge that has existed among people suffering from Usher Syndrome and their families for many years.

CRUSH study and database for unraveling Usher Syndrome

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

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

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’

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?

Zebrafishes hope for the future?

If you suffer from the Usher Syndrome, your eyesight increasingly deteriorates.
This cannot be prevented yet, but perhaps this will be possible in the future. Last February, a campaign was started for the development of a possible treatment for people suffering from Usher type 2a.

For many years, I was in the belief that there was no treatment for the disorder that I and my daughter suffer from. I am hard of hearing, I have a small field of vision and I know that eventually I will become completely blind. I also know that my daughter will go through exactly the same process. Then I heard at a meeting that there might be some hope after all. This happened to Maartje de Kok, campaign leader of The campaign team collects money for the development of a genetic treatment method for people suffering from Usher Syndrome. This method may stop the deterioration of the eyesight. Here the team closely works together with the MUS Foundation, a foundation that supports people suffering from Usher Syndrome and their families.

Stop deterioration
Maartje and others draw hope from the Zebrafish project, a gene-therapeutic study into the development of a treatment for people suffering from Usher type 2a (Usher 2a). ‘There is no treatment at all for Usher 2a yet’, Erwin van Wijk explains. He is project leader of the Zebrafish project and researcher at the Radboud UMC. ‘Therefore we as yet specifically focus on this type of Usher. (HIER HOUDT HET ARTIKEL OP DE WEBSITE OP) Usher Syndrome is caused by mutations in genes. A gene contains the genetic code for the production of one or more proteins. In case of Usher this involves proteins that are crucial for the functioning of the eyes and the ears. We know by now that faults (also called “mutations”) causing Usher Syndrome can be found in ten different genes.
With this research we try to achieve that, despite this deviation in the genes, a protein is still produced that remains functioning sufficiently. In this way we hope to be able to stop the deterioration of the eyesight.’

In order to accomplish this, another method is used than the ‘classic’ gene replacement therapy that researchers in the United States use for Usher type 1b. ‘The therapy for Usher 1b does not work for Usher2a’, Erwin says. ‘This is because the gene to be replaced in case of Usher 2a is so large, that this is technically impossible. We try to solve this problem by applying an alternative approach, the so-called exon-skipping method. Here the “fault” in the gene is masked (“skipped”) so the body does not include this producing a new protein. The protein of such a repaired gene is not completely perfect. It is a bit shorter and therefore it does probably not function for 100%. However, we hope that it will function sufficiently to stop the deterioration of the eyesight. We want to test the effect of this method on zebrafishes. This is because the eyesight of zebrafishes deteriorates when the Usher 2a gene has a deviation, just like with humans. This contrary to mice, for example.’

‘The story of the Zebrafish project came to me as a bombshell’, Maartje remembers. ‘For three weeks, I was just busy asking myself whether I would dare to devote myself to making this research possible. After these three weeks I though that I just had to have the courage to do so. Even if this were not for me any more, then perhaps for my daughter.’

Fight against yourself
The Usher Syndrome has a great impact on the life of Maartje. ‘I have two physical impairments that negatively strengthen each other. This is not only highly inconvenient, it also costs a lot of energy. I also have four children. I impose limits on them in the house, but at the same time I want to be a fine mother.’ Therefore Maartje is constantly fighting against herself.
When she was told that daughter Jente also suffers from Usher, she saw her life pass before here eyes. ‘Problems with choosing a study, give up sports, no more riding a bike. She will also have to go through all those painful moments and I can only guide her if I can keep dealing with this in a proper way.’ This is hard, because sometimes being deafblind is frightening, Maartje knows. ‘I have experienced a moment that I did not hear and did not see anything. I had the flue and I felt the deafblindness come over me. I was terrified.’
‘At the same time, I can better let go of the disorder since I had this experience’, Maartje continues. ‘For I am still here. I run, I write blogs, I participate in the organisation of a large campaign. Even if I can see nothing in the future, then I am still here and there are lots of possibilities.’ Nowadays, she cuts up every day in pieces. ‘My family is my mindfulness training. I always focus on one thing. When I am walking the children to the bus, then this is what I am doing. I must not dream away or take my mobile phone while I walk.’

Maartje is a member of the campaign team that will make the Usher Syndrome widely known in the coming period. ‘We particularly want to make people aware, share knowledge and collect money with happenings’, according to Maartje. The MUS Foundation will organise a national Usher day on 12 September. This day is both for people suffering from the Usher Syndrome and for parents, guides and professionals. There will be lectures as well as workshops, personal accounts and music.

The team members will also participate in Co-cycling, a pleasure ride organised by interns on 20 June. ‘Here we will certainly attract attention with our tandems and buddies’, she thinks. ‘Our image is playful, frivolous, creative and certainly not miserable. We just hope we may keep our eyesight.’

In good spirits
How big is the change that the deterioration of the eyesight can be stopped indeed? Erwin emphasises that there is still a long way to go. ‘The first experiments are very promising, but we are careful. The last thing we want is to arouse false hopes in people.’ There are still a lot of questions. ‘Does it really work for humans? Is it safe, are there no side effects?’ A lot of money is needed to find answer to these types of questions.

Maartje: ‘110.000 euros for starting up the study and 90.000 euros for setting up the database. This database is necessary for being able to explain individual differences. Just to be perfectly clear, we collect money for all people suffering from Usher Syndrome. In fact, this study may also offer perspectives for other types of Usher.’
Maartje is in good spirits that the money required will be collected. ‘Also thanks to the partners a lot can be done. We already organise events ourselves and we also want to mobilise people. Perhaps this research will be too late for our generation, but then just let’s do it for the next generation.’

What is Usher Syndrome?
Usher Syndrome is a hereditary disorder that can visit both men and women. This syndrome was in 1935 called after the Scottish ophthalmologist Charles Usher, who did extensive research into this syndrome.
People suffering from Usher Syndrome are hard or hearing or deaf on both sides from birth.
Besides, they later develop a bad eyesight as a result of Retinitis Pigmentosa (RP), an eye disorder that affects the retina. The consequences of RP mostly reveal themselves in the teenage years, but in some cases earlier. Sometimes the functioning of the organ of balance is affected as well.

Usher Syndrome comes in three different varieties: types 1, 2 and 3. People with type 1 are born deaf or very hard of hearing and they have problems with their balance. Their eyesight deteriorates already at an early age. People with type 2 are born hard of hearing and their eyesight increasingly deteriorates in their puberty or in their young adultery. Usher type 2 is the most common type. With the rare type 3 the hearing of people increasingly deteriorates, but less is known about the further development of the disease. The number of people suffering from the Usher Syndrome in the Netherlands is estimated to be 600-1000.

Source: Oogmagazine nr. 2, mei 2015
Text: Jeroen Wapenaar & Joke van der Leij

The small world of Machteld Cossee

Lisa Blom and documentary maker Hetty Nietsch followed the life of Machteld Cossee for six years. They stayed at the home of Machteld and her family and so recorded intimate moments in their lives.
How do you live your life knowing that one day your world will be quiet and dark? The central figure in the documentary ‘The small world of Machteld Cossee’ knows that she cannot escape her fate. Still, she tries to live a normal life for as long as possible. This results in touching moments as well as frustrations and rows and moments of fear for the future.

On her seventeenth birthday, Machteld is told that she suffers from Usher Syndrome. At that time she already is hard of hearing, but she will become blind as well. This message is a great blow to the family. Still it is rarely mentioned after this. Her father is a general practitioner and finds it hard to accept that there is nothing he can do for his daughter.
Machteld herself tries to build up an as normal as possible family life with her boyfriend and not to give in to her fear. Machteld: ‘When I think of it, it literally seizes me by the throat. So then I think, what will we have for dinner this evening?’
In the film we see what Machteld sees and hears, how she scans her surroundings, how she slowly becomes an outsider in her own life. How she fights with the desire to give a meaning to her own life. Machteld’s world is small already. There always is that fear: when will my hearing and my last bit of eyesight definitely disappear, making my world as small as it will get?

The documentary was shown earlier at the Dutch Film Festival in Utrecht on Wednesday 1 October 2014.
This documentary had its première on television at NPO2 broadcast by the VARA on 9 February 2015.

*The documentary has Dutch and English subtitling