Portret van oogarts Ingeborg van den Born

Is a treatment for USH 1B in sight?

De story of ophthalmologist Dr. Ingeborgh van den Born

Portret van oogarts Ingeborg van den Born

A natural development study for people diagnosed for Usher Syndrome type 1B was started already some time ago. This study is conducted in preparation to the clinical treatment trial (the project as a whole is called UshTher). How is this development study going and can on the basis of this study something be said already about the development of the disorder with people having mutations in the MYO7A gene? When will the UshTher clinical trial start and who will benefit from this gene therapy? Ingeborgh van den Born, ophthalmologist and specialist in retina pigmentosa working in the Oogziekenhuis in Rotterdam, the Netherlands, tells about this and answers our questions. 

How can someone find out exactly which disorder he or she is suffering from and in which Usher gene the changes (mutations) are found? 
It is to be determined by means of an extensive examination of the eyes and ears whether (serious) loss of hearing and retinitis pigmentosa (retina degeneration – RP) are involved. A DNA test is required for making the correct diagnosis. As a matter of fact, more syndromes are known (although very rare) that also affect these two senses. 
For a DNA test a small vial of blood is taken and a special laboratory will examine this for changes that can explain the loss of hearing and eyesight. Sometimes a vial of blood from one of the parents is needed as well to see if the changes are coming from one parent or have been inherited from both parents.  

Why is it so important to have a DNA test done? 
Usher Syndrome is rare, which makes the chance of a child suffering from Usher very small. For each form of congenital loss of hearing it is advised to conduct a genetic test to find the cause of this. 

This test can confirm Usher Syndrome, even if there are no problems with the eyesight yet. Promising therapies are being developed, but in order to be eligible to these, it is necessary to know what is genetically going on. Therefore it is really important to have this examined. The first steps towards developing a gene therapy for USH 1B have been taken. 

Gene therapy development is complicated and costs a lot of time and money. For instance, it took many years to develop the gene therapy product Luxturna®, which can now be used in the USA and Europe to treat patients suffering from retinitis pigmentosa (RP) caused by mutations in the RPE65 gene (Leber congenital amaurosis) in an early stage. Here the healthy gene is surgically placed below the retina. We hope this medicine will be available for Dutch patients in a couple of months. Currently, gene therapy studies are running for other RP-genes as well, but not for genes causing a type of Usher Syndrome. 

What is gene therapy and do you have any experience with this? 
The objective of gene therapy is to cure a hereditary disease or to mitigate the complaints. There are various possibilities for this. For instance, a healthy gene can be added to the own DNA from outside. The healthy gene is inserted into the cell using a weakened virus, which is called a vector. 
The AAV virus is suitable for bringing DNA into the cell, but this can only contain small pieces of DNA. Professor Alberto Auricchio of the TIGEM Institute in Naples has worked for many years on a technique that can bring the MYO7A in two pieces into the cell and there put the pieces together again (double AAV vector). If this turns out to be successful, this may be really promising for a number of other genes. 

At this moment, this technique is further developed and if the results are fine, we hope it can also be tested on people in a phase 1-2 study. Presently, it is too early to tell whether this can already be done in 2021. 

In Florida, USA, Shannon Boy started a study into the development of a gene therapy for USH 1B using a double AAV vector with the help of a large subsidy from Fighting Blindness.
This study is needs testing on a large animal model before the therapy can be tested for effectiveness and safety in a trial on test persons.  

What are the differences between these two studies? 
I do not know the details of the study of Dr Sannon Boye, but the technique seems to be similar to that of Professor Auricchio. It is a good thing when several laboratories are focusing on the same disease and on the same technique, for this will eventually lead to a higher quality and probably accelerate the process. At this moment, it is impossible to predict whether both studies will eventually result in a properly working medicine. 

In 2019, a natural development study on people suffering from USH 1B was started in Naples, Madrid and the Oogziekenhuis in Rotterdam, the Netherlands. This study is done in preparation to the gene therapy trial. In this study the development and any deterioration of the eyesight is monitored for a period of two years by means of three detailed eye tests. The information gained from this study will eventually be very important to be able to compare the effect of gene therapy with ‘doing nothing’ over some period of time. Many patients yearly go to their ophthalmologists for a check and there they undergo a number of eye tests, such as a field of vision test. 

What are the differences between the natural development study and an annual check? 
A study visit often includes more tests than the annual check by your own ophthalmologist. For instance, in this study two types of field of vision tests are done instead of one and each year photos and a scan are made of the retina. Additionally, these tests are to be done following a fixed procedure, making the data gained from the tests conducted in Naples, Madrid and Rotterdam easy to compare. 

Have you been able to include sufficient patients in this study? 
In view of collecting proper data about the natural development of this type of RP, it was agreed to include 50 patients spread over the three countries. Usher 1B is a very rare disorder and therefore we are happy to have eight Dutch patients participating. Some of them will soon come for their third and last visits. 

It is still possible to participate in this study. Of course, this will take extra time and effort to go to the Oogziekenhuis in Rotterdam for a full day, but expenses and the like are compensated. The study includes a total of three study visits always with one year in between. 

Patients who want to participate in this natural development study can contact me (Dr Ingeborgh van den Born) or Ms Marja Scheeres (tel.: 010-4023437, e-mail: roi@oogziekenhuis.nl). 

The Usher Syndrome Foundation wants to stimulate scientific research into the unravelling of and treatment for Usher Syndrome. Our mission is to have a treatment for Usher Syndrome in the year 2025. We want this for all patients, so for patients diagnosed for USH 1B as well. In the laboratory of the Radboud UMC research is mainly done into USH 1F, 2A and 2C and probably soon 1D as well. At this moment, no research is done into a treatment for USH 1B in the Netherlands. 

Can patients who are participating in the natural development study also participate in the UshTher clinical trial when this will be started? 
We have highly detailed information about the eyes of the people participating in the natural development study and we assume that some of them will be eligible to participation in the treatment study. Participation in treatment studies is often subject to strict criteria.  

Can Dutch patients who have not participated in the natural development study for USH 1B be eligible for participation in the UshTher clinical trial? 
This will probably be possible, provided that these people meet the inclusion criteria. 

Is the UshTher gene therapy promising for all patients suffering from USH 1B? 
The objective of gene therapy is to make the new, healthy gene improve the functioning of the affected retina cells and so slow down the process of the disease. This implies that this therapy can only work if there still is a minimum number of functioning retina cells. Consequently, patients who are blind and have no or hardly any functioning cells left, will not benefit from this type of therapy. 

Are there any hopeful developments for older patients suffering from USH 1B who have already lost many light-sensitive photoreceptors? 
As said above, unfortunately gene therapy will not help everyone and this means that research into other types of treatment, such as stem cells and, for instance, a light-sensitive chip is just as important.  

What do you think is the quickest and most effective path to a treatment for Dutch patients suffering from USH 1B? 
I think an important step has already been taken, being the cooperation from the Netherlands with the institute of Prof Auricchio. It is also very important that the Usher Syndrome Foundation itself also actively keeps in contact with him and the TIGEM institute. Eventually, it is all about cooperation between patients (associations), scientists and physicians.  

Additionally, we are working with rare disorders and therefore registration of patients is essential too. Besides, as you have also mentioned yourself, DNA tests are important to gain a good overview of the various mutations and genes of Dutch patients. By participating in the Ushther project we hope to make a contribution to the development of a treatment for Usher 1B.  

The Usher Syndrome Knowledge Portal provides additional background information about, among other things: 

Erwin van Wijk links in beeld, rechts naast hem een waterbak met kleine zwemmmende zebravisjes

The developments in the research laboratory

Erwin van Wijk links in beeld, rechts naast hem een waterbak met kleine zwemmmende zebravisjes

Despite the corona crisis, which has dominated our country for some time and as a result of which the research laboratory of Erwin van Wijk in the Radboud UMC for some time, quite some progression was made in the past year. Below you will find an overview of the most important achievements of last year. 

‘Genetic patches’ 

  • ProQR Therapeutics published the very promising intermediate results of the Stellar last April! In this Stellar trial the first group of people (with ‘faults in a specific part of the USH2A gene (exon13)) were treated on an experimental basis with the QR-421a molecule, the scientific basis of which was laid in the Radboud UMC. For this also take a look at ProQR publishes the first results of STELLAR’ or the website of ProQR Therapeutics, which Erwin and his colleagues closely cooperate with.
  • This year also saw significant progression in the development of ‘genetic patches for four other parts of the USH2A gene. More information will be provided about this in the course of the year 2021. 
  • We set up the Dutch Center for RNA Therapeutics together with the LUMC. In this centre we will develop genetic patches for covering extremely rare hereditary faults. Extremely rare means that they occur only once or twice in the whole world. The development of the layout and the set-up of the centre portal is still in full swing. Here you can read additional information about the foundation of the DCRT: A genetic patch for very rare mutations. An update will follow in the course of this year.  
  • In cooperation with the research group of Dr Monte Westerfield and Dr Jennifer Phillips (University of Oregon, USA) and the USH1f Collaborative, we expanded the genetic patch methodology to the PCDH15 gene (= Usher syndrome type 1F). 

Minigene therapy 

  • The development of a minigene therapy for Usher syndrome type 2C was started in April 2020. This is a four-year PhD project financed with contributions from the Usher Syndrome Foundation, LSBS and CureUsher. A part of this project also included further optimisation of USH2A minigenes

Study into quality of life: Sleep study 

  • Apart from their visual impairment, many people suffering from hereditary poor eyesight and Usher Syndrome also have sleeping problems, possibly as a result of a deviating day-night rhythm. These problems have a great impact on the well-being of patients suffering from hereditary blindness, but they are hardly recognised as a part of the disorder. We wrote a four-year research proposal aimed at gaining a better understanding of this problem, making the scientific world, care professionals and health insurance companies recognise this and, finally, solving this by having it included as a part of the current care paths. After assessment by a scientific committee, the project ended up in the top 3 of best projects! About two thirds of the required funds have been assigned by ANVVB, LSBS, Stichting Beheer het Schild, the Gelderse Blindenstichting en the Usher Syndrome Foundation. At this moment we are raising the remaining part of the required funding so that we can actually start this important study by mid-June 2021! Read more about ‘Recognition of sleeping problems with patients’. 


Documentary Silence Night

Would you rather be deaf or blind? Joyce de Ruiter (36) from the Netherlands can’t choose, she eventually will be deaf and blind because of Usher syndrome. Her path to acceptance was accompanied by three burn-outs, but now she uses the diagnosis as her strength, she gives lectures and is a source of inspiration for many.
In the Campusdoc documentary Silence Night (Dutch: Stilte in de nacht) we follow her path to acceptance and show the viewer how she deals with the fact that she is a source of inspiration for many.

Usher syndrome
Usher syndrome is a rare genetic disorder in which children are born deaf or hard of hearing and experience a progressive loss of sight in addition to night blindness. Sometimes there are also balance problems. In the end, people with Usher syndrome become deaf and blind.

About the makers and Campusdoc
Milou op ten Berg and Lisanne van Spronsen are the makers of this documentary. They are both third-year students at the School of Journalism in Utrecht. Through Lisanne’s mother she heard Joyce’s story and felt that more recognition should come for Joyce, but also for the syndrome.

They decided to sign up together for the Campusdoc, a special minor in which a total of twenty students will make ten documentaries, which (if covid-19 permits) will premiere in the Louis Hartlooper Complex in Utrecht in the week of 18 January. During the film festival, a professional jury will decide who wins the jury prize. After this, the documentary will be screened at other international film festivals.

To make this film a reality the filmmakers need some money. This way we can make the documentary as special as Joyce her story is. Fifteen percent of the entire proceeds they donate to Stichting Ushersyndroom, so that they in turn can have research carried out into a treatment. Their target amount (7,000 euros) has almost been reached, but with even more money they can also have the film premiered (corona proof) and more money will automatically go to Stichting Ushersyndroom. You can make a donation here Cinecrowd/Stilte in de nacht. 


Do you want to follow the process of this documentary?
website ‘Stilte in de Nacht’ 
Instagram @stilteindenacht
Facebook @stilteindenacht

Cinecrowd/Stilte in de nacht.


HURRAY! Everything you want to know about Usher Syndrome has now been put together!

Stichting Ushersyndroom launches the Usher Syndrome knowledge portal. 

Today, a long-cherished dream of many families confronted with Usher Syndrome will come true. So far, information and knowledge about Usher Syndrome were hard to find and highly fragmented. The Usher Syndrome knowledge portal is made available by the Stichting Ushersyndroom and it will be officially launched by Dr. Ronald Pennings of the Radboudumc in Nijmegen, the Netherlands, with a festive touch. 

Stichting Ushersyndroom (formerly Stichting MUS) was established in the year 2012 from a need to share experiences and information with each other. When being diagnosed for Usher Syndrome, you have the ‘sword of Damocles’ hanging above your head and you will have a lot of questions, such as: ‘How can I live my life knowing that my child will become both deaf and blind?’
Today, Stichting Ushersyndroom will launch a portal that has been developed for and by people suffering from Usher Syndrome in which they as Usher experts by experience have put together all their knowledge and information. If you want to help us further develop the knowledge portal, please contact us through kennisportaal@ushersyndroom.nl.

Festive touch
Ronald Pennings, MD, PhD, ENT consultant and Usher syndrome specialist of the Radboudumc in Nijmegen, will virtually open this portal with a festive touch.

Renewed campaign site
Simultaneously with the development of the knowledge portal, Stichting Ushersyndroom also gave the campaign site a new look. You can easily switch between the campaign site and the knowledge portal using the footer at the bottom of each page of the website.

Sharing knowledge and information is essential for unravelling Usher Syndrome. Usher Syndrome is a serious hereditary disorder that has a far-reaching impact on the lives of people suffering from Usher Syndrome and their social environments. We wish to eliminate this disorder from the bottom of our hearts. Therefore Stichting Ushersyndroom has formulated the following mission: ‘A treatment for Usher Syndrome in 2025!’

Support us and make our dream come true!

ProQR announces first results from STELLAR

Summary of Phase 1/2 Interim Analysis of QR-421a for Usher Syndrome Program

A first-in-human clinical trial of QR-421a is ongoing. The Phase 1/2 study, named Stellar, includes adults that experience vision loss due to mutation(s) in exon 13 of the USH2A gene. This Phase 1/2 clinical trial is designed to evaluate the safety and tolerability of QR-421a. Patient benefit will be assessed as well.

Three-months interim findings from Stellar, reported in March 2020, suggested QR-421a given as a single intravitreal injection was safe and well tolerated. QR-421a showed early and encouraging evidence of activity, with 25% of patients showing a benefit across multiple concordant outcome measures and was well tolerated with no serious adverse events. Two of eight participants in the treated groups responded to QR-421a treatment thus far showing benefit in multiple outcome measures.

Across both cohorts thus far, QR-421a was observed to be generally well tolerated with no serious adverse events noted. Based on these early positive findings we will continue the trial as designed at expert centers in North America and select European countries.

Read here the PDF:  Interim Findings of QR-421a Phase 1/2 Clinical Trial for Usher Syndrome and nsRP 

Read press release: ProQR Announces Positive Findings From an Interim Analysis in the Phase 1/2 trial of QR-421a for Usher Syndrome and Provides Business Update


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


A tailor-made genetic patch for very rare mutations

New centre for RNA therapy set up for small patient groups.

Scientists and physicians of the Leiden University Medical Centre (LUMC) and the Radboudumc together started the Dutch Center for RNA Therapeutics (DCRT). This new virtual centre was set up with the objective to develop tailor-made RNA therapy. A therapy meant for patients with rare genetic disorders, such as Usher Syndrome.

Dutch Center for RNA Therapeutics
The DCRT opened its doors for the first time on 29 February 2020, Rare Disease Day. The DCRT is the first centre in Europe to develop RNA therapy for very rare diseases. This is about genetic diseases and mutations that are so rare, that it is less interesting for pharmaceutical companies to invest in developing a treatment. The therapies are targeted on stopping or slowing down progressive genetic eye, brain and muscle diseases by local administration of medication.

RNA therapy for Usher Syndrome
The objective of RNA therapy, also called AON therapy, is to repair the genetic defect at RNA level, so that a smaller but partly functional Usher protein can be made.
For a specific mutation an antisense oligonucleotide can be designed. Antisense-oligonucleotides, abbreviated by ASOs or AONs, can be regarded as a ‘genetic patch’ that covers the area of the mutation and makes it invisible. In this way the cause of Usher Syndrome is removed and, hopefully, the deterioration of the eyesight (and possibly hearing) with this group of patients can be stopped or mitigated.
Erwin van Wijk of the Radboud UMC in Nijmegen, the Netherlands, studies the therapeutic effect of antisense oligonucleotides (AON) for the future treatment for Usher Syndrome.
Jennifer Lentz from New Orleans (LSU School of Medicine, USA) is working on the development of an antisense oligonucleotide (AON) for patients with a specific mutation in the USH1C gene, the c.216G>A mutation.

Over 500 different mutations are known for the USH2A gene and RNA therapy is not possible for all these mutations. RMA therapy will be possible for about one third of the people with mutations in the USH2A gene, but some mutations are extremely rare. The new Dutch Center for RNA Therapeutics (DCRT) wants to develop tailor-made ‘genetic patches’ for this really small group of patients.

‘It is impossible for the industry to make medicines for only a few patients. Therefore it is the duty of the academic hospitals to be there especially for that group’, according to scientist Anniemiek Aartsma-Rus.

The in-house making of a ‘genetic patch’ for one specific mutation has one factor that saves a lot of time. No registration with the European Medicines Agency (EMA) is required.
Together with patients’ associations and subsidies this centre must be developed further in order to make sure that an (affordable) ‘genetic patch’ will be available for all patients with (very) rare mutations in the Usher gene in the future.

The DCRT is made possible by a financial contribution of the Human Genetics department of the LUMC. This non-profit centre will be managed by Dr. Willeke van Roon-Mom and Prof. Annemieke Aartsma-Rus of the Human Genetics department of the LUMC Also neurologists Dr. Erik Niks and Prof. Jan Verschuuren, ophthalmologists Prof. Camiel Boon and Prof. Gré Luyten and hospital pharmacist/clinical pharmacologist Prof. Henk-Jan Guchelaar are involved in this as well. Apart from Dr. Collin, geneticists Prof. Frans Cremers, Dr. Susanne Roosing and Dr. Alex Garanto as well as Dr. Erwin van Wijk as researcher of the ENT department, ophthalmologist Prof. Carel Hoyng and ENT specialist Dr. Ronald Pennings from Nijmegen are involved in the DCRT as well.

ProQR Therapeutics from Leiden has further developed the antisense oligonucleotides (AON), developed by Dr. Erwin van Wijk, into the medicine QR 421a and this is currently tested for effectiveness and safety in a trial called STELLAR. This is a ‘genetic patch’ for exon13, the most frequently occurring mutation in the USH2A gene. The first results will soon be published.
The ‘genetic patch’ must be regarded as a medicine and not as a gene (replacement) therapy. This is because actually no gene is replaced or repaired. The ‘patch’ must be administered repeatedly in order to have a permanent effect on the deterioration of the eyesight.

Development of gene therapy for large USH2C gene

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

Know your gene!

Join the CRUSH database

Usher Syndrome is a rare hereditary disease. In the Netherlands, about 1000 people suffer from Usher Syndrome, but far from everyone has been diagnosed.
Now that the scientific developments are going really fast, the Stichting Ushersyndroom calls on everyone to have their DNA tested and to register with the National Usher Syndrome Expert Centre of Radboudumc in Nijmegen, the Netherlands.

Our dream
The dream of all people who are confronted with Usher Syndrome in their daily lives is that researchers will in time find a treatment to stop the deterioration of eyesight and hearing.
Our dream can come true when all patients with Usher Syndrome know their gene and mutation.
In connection with the new privacy law people suffering from Usher Syndrome are hard to reach and patient files are no longer passed on to other specialists and hospitals.
By taking action yourself and to register yourself in the international CRUSH database of the national Usher Syndrome Expert Centre you contribute to sooner finding a treatment.

Start setting up your own patient file!

Ask your therapists for your medical data, such as audiograms, eyesight measurements, visual field tests, genetic and other results, and keep these at home in a file.

As soon as a study is started, you will be asked to participate. Then it will be convenient to already have your own patient file at hand. Specialists can see whether you meet the criteria of any study based on your own file. You can now register for the CRUSH database, so your contact data will be known already.

Do you want to know how you can ask for a DNA test? Please go to the knowledge portal for further reading.

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+