Two groundbreaking projects awarded

‘Moon Rocket Grant’ awarded to two groundbreaking projects

At this moment, there is no treatment yet for Usher Syndrome, a disorder that globally 400.000 people suffer from. In order to find a treatment that can stop, slow down or even reverse the process of becoming both deaf and blind, more knowledge and research into Usher Syndrome are needed.

Therefore Stichting Ushersyndroom (The Dutch Usher Syndrome Foundation) presents the ‘Moon Rocket Grant’: € 200.000, – for research into Usher Syndrome with a maximum of € 100.000, – for each study.

The Moon Rocket Grant
Stichting Ushersyndroom has launched the Moon Rocket Grant: a large pot of money for pioneering research into (a treatment for) Usher Syndrome. The objective of the Moon Rocket Grant from the Stichting Ushersyndroom is to effectuate a moonshot formulated by us: ‘A treatment for Usher Syndrome in 2025!’ This moonshot includes all types and subtypes of Usher Syndrome.

The study proposals must fit in with one of the four core values of the ‘Moon Rocket Grant’: Treatment, Knowledge, Diagnostics and Impact.
Every study (fundamental, translational or clinical) must lead to a treatment option, more knowledge and understanding, better diagnostics and an increase of the impact for every type of Usher Syndrome.

The Medical Advisory Council extensively tested and assessed all submitted study proposals. After this first assessment there was a second round: an on-line presentation with a short interview, after which the final selection for the award was made.

The Moon Rocket Grant goes to …..

Stichting Ushersyndroom announces with pleasure that two projects are eligible for the Moon-Rocket Grant 2022.

Prof Mariya Moosajee (UCL Institute of Ophthalmology, London, UK), will receive € 100.000, – for the project:

Prof Mariya Moosajee

“Large Gene Augmentation with non-viral episomal vectors for Usher syndrome”

Use of non-viral plasmid vectors for Usher Syndrome
It is well-known that the AAV (adeno-viral virus) vector is used for gene therapy, but this vector has a limit to the size of the gene. Most Usher genes are way too large for being packed into an AAV vector. When applying gene therapy to the retina of patients using the AAV vector, sometimes thinning of the retina (also called atrophy) can develop. Therefore alternative ‘packaging’ vectors are to be found for future gene therapies for Usher Syndrome.

Prof Mariya Moosajee has in cooperation with Dr Richard Harbottle (DKFZ German Cancer Research Centre, Heidelberg) developed a DNA plasmid (USH2A-S/MAR-vector) which can hold the full-length USH2A-DNA.
The DNA plasmid has been tested in a zebrafish model as well as in patient cells taken from a skin biopsy.

Prof Mariya Moosajee will use the ‘Moon-Rocket Grant’ to test the system of DNA plasmid in an already existing rabbit model for USH2A.
If the application of this alternative gene replacement strategy turns out to be successful, this will have a great impact for all inherited reti

nal diseases. After this study, it may be possible to start a phase 1 clinical trial for patients and it also may offer solutions for other large Usher genes. Gene therapy making use of DNA plasmid may have additional advantages; application (several times) with a limited immune response. Prof Mariya

Moosajee hopes this approach will be safer and can avoid some of the complications that are seen in the current viral gene therapy. This project will at least take 2 years and has been budgeted at over € 200.000. Moorfields Eye Charity and Cure Usher will also be contributing to this project. With the contribution of the ‘Moon Rocket Grant’ from the Stichting Ushersyndroom the budget has been covered and the study can start.

The second project to be financed by the Moon Rocket Grant is the study of Monte Westerfield (Neuroscience, university of Oregon) and Erwin van Wijk (Radboud University Medical Center, Nijmegen, the Netherlands) entitled:

Prof. Monte Westerfield and Dr. Jennifer Phillips

“Exon-skipping as a future treatment for USH1F associated retinal disease” 

In this collaborative study Monte Westerfield of the University of Oregon and Erwin van Wijk of the Radboud UMC will develop and evaluate a treatment for Usher syndrome type 1F-related retinal disease based on the exon skipping methodology.

About 20.000 people worldwide lose their eyesight as a consequence of PCDH15 mutations. This condition is named USH1F.
The PCDH15 gene codes for the protocadherin 15 protein (PCDH15 protein) and is essential for normal eyesight and hearing. The PCDH15 protein contains multiple predicted extracellular cadherin (EC) domains. Many USH1F patients have mutations in the region encoding the EC domains number 6 (EC6) and 7 (EC7), resulting in a non-functional or even absent PCDH15 protein.

The ultimate goal of the researchers is to develop a treatment that halts the progression of PCDH15-associated visual dysfunction. For this, they will adopt the principle of “exon skipping” and develop a “genetic patch” that will instruct the light-sensitive cells inside the eye to skip the region of the PCDH15 gene that codes for the EC6 and EC7 domains. In this way a somewhat shorter but hopefully still functional PCDH15 protein is produced, specifically lacking the EC6 and EC7 domains.

A pilot study exploring the therapeutic potential of “exon skipping” for USH1F was conducted some years ago. In this study the researchers targeted another domain in the protein, but this did not result in a restored function of the PCDH15 protein. With the knowledge gained in the past few years the researchers can now better predict whether or not the remaining protein after exon skipping will be functional. Based on these improved prediction tools they now opt for “skipping” the region encoding EC domains 6 and 7.
In previous studies of both Monte Westerfield and Erwin van Wijk it was shown that zebrafish are suitable animal models for this study. To obtain functional proof for the proposed concept of skipping the EC6-EC7 encoding region of PCDH15, the researchers aim to remove this part of the PCDH15 gene from the zebrafish genome and analyze whether these ‘treated’ zebrafish will have a better eyesight than the untreated mutant zebrafish with USH1F mutations.

This research project was budgeted at € 100.000, – for a period of 24 months.

The objective of Stichting Ushersyndroom is to finance scientific research that is to lead to a treatment that will show down, stop of even reverse the deterioration of hearing and eyesight. Apart from this, the foundation also (financially) supports the improvement of the quality of life, the growth of knowledge and information about Usher Syndrome and to enhance the contact between fellow-sufferers.

You can also donate directly to Stichting Ushersyndroom by using the QR code.

 

 

 

Study into the best approach of USH1B

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Stichting Ushersyndroom (Dutch Usher Syndrome Foundation) announces with pride its financing of a study that will test the best approach for USH1B (gene) therapy by making use of, among others, patient-specific cell models and a large animal model. This may take a (gene) therapy for USH1B to the pre-clinical phase. Dr. Kerstin Nagel-Wolfrum, who works at the Johannes Gutenberg University in Mainz, will lead this project.

Children suffering from Usher Syndrome type 1 (USH1) are born deaf and with a non-functioning organ of balance (the vestibular system). The first signs of loss of eyesight, such as night-blindness and a decreasing field of vision, will present themselves later in the childhood period. USH1 is most often caused by mutations in the MYO7A gene (USH1B). About 14% of all people suffering from Usher Syndrome has type 1B. The MYO7A gene is a very large gene and the Myosin protein is also called a motor protein. Is has a ‘head and a tail’ and therefore it must be replaced or processed as a whole when developing a gene therapy.

New approaches
The large size of the MYO7A gene makes classical gene therapy using an AAV vector impossible. However, new approaches, including double and triple AAV vectors, mini-genes, prime editing, translational read-through and exon skipping, are promising new alternative therapeutic strategies. Please go to the Knowledge portal for further reading.

From skin biopsy to mini-retina
With the help of a skin biopsy from a USH1B patient (fibroblast), Dr Nagel-Wolfrum can further develop these molecular cells into a retinal pigment ephithelium (RPE) and a retinal organoid (RO). The retinal pigment epithelium is found between the retina and the choroid and it clears away the waste products of the rods and cones in the retina. The retinal organoids are also called the mini-retinas.

The possibility to model retinal disorders by means of fibroblasts into mini-retinas created unprecedented opportunities in the research area.

Dr. Kerstin-Nagel-Wolfrum

Gain insights and test therapies
By making use of the ‘mini-retinas’, Dr Kerstin Nagel-Wolfrum will gain more insight into the mechanism that damages the retina and causes loss of eyesight. Apart from this, she wants to subject these retinal organoids (mini-retinas) to various therapies in order to test them for their effectiveness and functionality. Dr Nagel-Wolfrum will also test the mini-genes by conducting an AAV vector-based gene therapy.

On to the pre-clinical phase
A large animal model, a USH1B pig, has already been developed and is ready for testing possible therapies. Dr Nagel-Wolfrum will apply the therapy that the pre-study with the retinal organoids (mini-retinas) has shown to be the most effective one when doing research on the pig model. This study is called the pre-clinical phase. If this pre-clinical phase leads to positive results, this can be promising for a possible therapy for patients.

In this project Dr Kerstin Nagel-Wolfrum closely cooperates with:

  • U. Wolfrum (Institute for Molecular Physiology, JGU Mainz, Germany): USH1B pig model
  • S. Gerber (University Medical Centre Mainz, Institute of Human Genetics, Germany): Bioinformatics
  • M. Cheetham (UCL, London, United Kingdom): iPSC-RPE and iPSC-RO generation
  • V. Kalatzis (Institute for Neurosciences of Montpellier, France): iPSC-RPE and iPSC-RO generation
  • J. Gopalakrishnan (Heinrich-Heine University Düsseldorf, Germany): brain organoids

This project will have a duration of 1 year and has been budgeted at
€ 100.000, -. Stichting Ushersyndroom hopes that this study will contribute to the development of one or more effective treatments for people suffering from Usher Syndrome type 1B.

View the PowerPoint presentation about this research by Dr. Kerstin Nagel-Wolfrum

Looking back at 2022

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One year ago the Usher Syndrome Foundation announced its reaching the milestone of 1 million euro of donations. A huge and almost magical amount of money! Thanks to the many donations, actions and events we reached this amount six years after the first start of the campaigns. This has enabled us to finance a number of scientific studies.

The special milestone of 1 million gave everyone wings. And this was shown in the year 2022!


We collected almost half a million euro of donations in one year! Thanks to all contributors and thanks to you!

Thanks to the many donations and gifts, we can finance several new (inter)national research projects.
The first 2 new studies that we will fund have already been announced at the end of December 2022. We will announce the two funded studies from the Moon Rocket Grant and another new research project in early 2023.

The start in 2022
The year started with a change in the board and expansion of the board: Diede Heijkoop took over the function of secretary from Annouk van Nunen. Johan Driessen joined the board as a member and was given the fund-raising portfolio. After a short familiarisation period the board started with the development of a Strategic Plan. Where are we now and where do we want to go? And how do we expect to get there?
We have the moonshot “A treatment for Usher Syndrome in 2025!”, but we are looking further ahead. The Stichting Ushersyndroom wants a ‘moon landing’ in 2030. After a year of interviews, away days, on-line meetings and many discussions, we are now busy developing a Strategic Plan. We will present this plan early in the year 2023.

Ivonne Bressers appointed Knight of the Order of Orange Nassau
King Willem-Alexander appointed Ivonne Bressers (56) Knight of the Order of Orange Nassau. As chairwoman and driving force behind the Stichting Ushersyndroom she is of invaluable for the Usher patients group. Mayor Marcouch presented the decoration during the rain of titles at the town hall of Arnhem.. Read more …

A visit to the researchers
The board received a progress report with respect to all ongoing studies (co-)financed by the foundation. Because of the renewal of the board and also in view of the major financial contribution that the foundation makes to scientific research, the board went to visit the researchers in the Radboudumc. The board was given a presentation and a tour for each study. Sometimes big steps are made in one year, but sometimes there also are setbacks to cope with.

Mini genes 2a: this study was patented. Researchers are talking about further cooperation with companies. Which company wants to take part in the pre-clinical phase in order to lift the study to the next level? Read more ….

Mini genes 2c: the sticking together of small coding ‘pieces’ of the gene to make a mini-gene-2c was disappointing at first, but after a few months delay and several attempts, the researcher succeeded in this! At the same time, another researcher was developing an innovative tool with which predictions can be made with the help of the computer whether a protein will or will not be functional. This made clear that the mini-genes-2c required minor adjustment. These adjustments are presently being made and will subsequently be tested. Read more …

CRUSH-study: Most CRUSH participants will be called for the very last time in the coming year. The study is heavy and burdensome for the participants. However, the analyses and results are of great value for the researchers and all people suffering from Usher Syndrome. The results will be of help in future treatments. In order to hearten the participants of the CRUSH study, they all received a small present from the foundation. The presents are handed out to the participants with each visit. Read more …

Sleep study: Many interview were held during the first year of this study. This showed that there is a clear difference between the control group and the group of people suffering from Usher Syndrome. These people had much more sleeping problems, especially with respect to sleeping on. What exactly is going on? For answering this question zebrafishes are used as animal models. We hope to know more next year. Read more …

USHIII: The ‘USHIII Initiative’ spent a large part of the past year on going through all procedures for an application with the FDA in order to be able to start the trial. Preparations are being made. The commitment of Dr Ronald Pennings and Dr Suzanne Yzer is mainly focused on the natural development study and based on data from the past that are already available in existing medical files. Read more …

Mini retinas 2a: The progress report was received. Early next year, a delegation of the board and the Medical Advisory Council will visit the LUMC where the study is conducted. This study was started at the end of last year. Read more …

Discovery of a new type of Usher Syndrome: type 4
The Radboud UMC has proven the existence of another type of Usher Syndrome. People diagnosed for type 4 are born with good hearing and eyesight, but these will both gradually decrease as the patient gets older (from the age of 17). Read more …

Global Usher Awareness Day 2022
Every year on the third Saturday of September, we celebrate ‘Global Usher Awareness Day’. On this day, which falls on the same day as the autumn equinox, the sun is directly above the equator and the day and the night have the same length. Following the autumn equinox, there will be less light every day; days get shorter and nights get longer.

Usher? So what!
Especially for the Global Usher Awareness Day the Usher Syndrome Foundation published a video podcast series with Joyce de Ruiter and Femke Krijger, in which they talk about their ‘USH-life’.

Joyce is ambassador of the Usher Syndrome Foundation, author and professional speaker. She published, among others, the book ‘Niet horen, niet zien, niet zwijgen’ (not hear, not see and not keep silent). Femke is shiatsu therapist and inspirational speaker and she recently published her book ‘De evenwichtskunstenaar’ (The balance artist). This podcast series consists of 7 episodes, each covering a new subject. Watch and listen (CC English) ….

How do they do that?
On our socials in the section ‘Hoe doen zij dat?’ (how do they do that?) random Ushers and/or their parents are asked five pressing questions. These are question that everyone can answer. The inspiring and motivating stories were put together in this on-line magazine especially for the celebration of Global Usher Awareness Day ’22. Read magazine {Dutch} …

Let USH Talk
On October 15, the Stichting Ushersyndroom organized the first edition of Let USH Talk, a series of interactive online events about (living with) Usher Syndrome. In the first edition, Dr. Ronald Pennings and Dr. Suzanne Yzer talks about the diagnosis interview together with the other guests and the online audience. Afterwards, the participants could meet and talk digitally in the online breakout rooms.

The 2nd edition is planned for February 4, with the theme “Loss & Resilience” and will include Prof. dr. Dr. Em. Manu Keirse join the chair of the day Wendelien Wouters. Joyce de Ruiter and Lotte Driessen (both live with Usher syndrome) will join the table. Read and watch (Video CC English) …

Long-awaited patients’ brochure finally available
The brochure: ‘Ushersyndroom’ (Usher Syndrome) will be available as from mid October in the webshop of the Usher Syndrome Foundation. The production of the patients’ brochure was an extensive process; from writing, selecting pictures and photos to design development. With the launch of the patients’ brochure a long-cherished wish of the foundation came true. The brochure is intended for everyone who has been diagnosed for Usher Syndrome, but in particular also for their family and social surroundings or people who are otherwise interested in Usher Syndrome. Read moren (Temporarily only available in Dutch) ….

Usher4Usher
Sometimes you want to come into contact with fellow-sufferers or parents of ‘Usher’ children. The request are diverse, from teenagers to adults and parents who sometimes also want to physically meet people. Usher4Usher mediates in these contacts. Mail to: contactgroep@ushersyndroom.nl

Tears as a source of information?
Can tears provide information that may be important for better diagnostics and monitoring in future treatments of USH1b patients?
In the pilot study “Investigating the exosome content as a novel marker for Usher syndrome 1b” Dr Irene Vazquez Dominguez, working at the Radboud UMC, will study tears. She hopes to find any indications that tears can be a source of information and may contribute to a better prediction of the development of Usher Syndrome type 1b.
This study will be financed by the Stichting Ushersyndroom with co-financing from Usher Syndrome Ireland  Read more ….

Reggeborgh supports Stichting Ushersyndroom en Radboudumc
Reggeborgh supports the 4-year study ‘Development of Exon Excision Therapy’ by Dr. Erwin van Wijk and dr. Erik de Vrieze at Radboudumc. In this research, the aim is to permanently remove specific exons in which patients have hereditary mutations from the DNA of the photoreceptors in the retina and/or the hair cells of the inner ear using the CRISPR/Cas9 gene editing technique. The aim of this strategy is, with a single treatment, to stop the deterioration of vision (and in time hopefully also of hearing) in larger groups of patients who have mutations in these exons of the USH2A gene.
An incredibly important and hopeful research!
We would like to thank Reggeborgh for making this research possible! Read more ….

Moon Rocket Grant
The Stichting Ushersyndroom presented the ‘Moon Rocket Grant’ early in the year 2020: researcher from all over the world could submit study proposals and had the chance of receiving a subsidy of € 100,000.-. The foundation made 2 x € 100,000.- available for this ‘Moon Rocket Grant’.

The foundation was able to present this Grant thanks to the many donations. The Grant was internationally appreciated and the applications included various Usher genes and Usher Syndrome types.
The foundation will announce which researchers will receive a subsidy of €100,000.- for their study proposals early in the year 2023. Read more ….

The Medical Advisory Council
Other than former years, last year was a busy year for the Medical Advisory Council. The members of the Medical Advisory Council had to assess several study proposals that the Usher Syndrome Foundation received from Uitzicht. Apart from this, the Medical Advisory Council set up the entire Moon Rocket Grant and they designed the application form. The Medical Advisory Council also studied and assessed all applications for the Moon Rocket Grant.
Willem Quite will terminate his function as member of the Medical Advisory Council by the end of this year. After 6 full years of intense involvement he will leave the Medical Advisory Council and Donna Debets will take his place.

A book, a TedTalk and interviews in newspapers and magazines
Femke Krijger wrote her first book: De Evenwichtskunstenaar (The balance artist). Joyce de Ruiter held her first TedTalk and many people suffering from Usher Syndrome were interviewed for newspapers and magazines.

Run, cycle, walk, collect returnable bottles and crotchet oven cloths
This year was filled with wonderful actions and initiatives! For example, over 100 people joined in the Run4Usher during the Zandvoort Circuit Run. Tim Schroeder made his gigantic cycling trip to Alicante and will make a gigantic cycling trip again in 2023. Wilte Jager cycled the 11-city race in 24 hours with his tandem buddy. The first edition of NL wandelt voor Usher (The Dutch walking for Usher) turned out to be a huge success. The Run4Usher during the 7 Hills Run was a feast of unity and the gallery of the many bottle deposit actions is growing steadily. On WhyDonate we see a number of other wonderful actions that were organised for the Usher Syndrome Foundation in the past year: Billie for Usher, Crosse for Josse, Tennis tournament and clinic HOT in Nieuw and also Team Lente took up a sportive challenge.

Really great actions were organised for the foundation on the action platform Support & Donate as well: The A-team took action for the Usher Syndrome Foundation and Tim van der Avoird did his most heavy sportive challenge ever.

There also were runs during the Marathon of Rotterdam  and the Wateringse Veldloopfestijn and in Breda, the 40 kilometres of the Canal Run were run by the famous ’40 of Breda’.

Social media, website and mailbox
Apart from all the above-mentioned actions, other individual actions were organised and money was donated. People knew how to reach us through website, mail or other social media channels. Thank you very much!

 

The objective of the Stichting Ushersyndroom is to finance scientific research that is to lead to a treatment that will show down, stop of even reverse the deterioration of hearing and eyesight. Apart from this, the foundation also (financially) supports the improvement of the quality of life, the growth of knowledge and information about Usher Syndrome and to enhance the contact between fellow-sufferers.

You can also donate directly to Stichting Ushersyndroom by using the QR code.

 

 

 

Tears as a source of information?

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Stichting Ushersyndroom and Usher Syndrome Ireland

finance research into USH1b

Can tears provide information that may be important for improving diagnostics and monitoring in future treatments of USH1b patients? In the pilot study “Investigating the exosome content as a novel marker for Usher syndrome 1b” Dr. Irene Vázquez Domínguez, who is working at the Radboudumc (Nijmegen, the Netherlands), will investigate tears. By doing this, she wants to assess whether there is any indications on tears that can be employed as a source of information and therefore may contribute to not only increase the current knowledge of the disease but also to allow better prediction of the development of Usher Syndrome type 1b.

This study will be mainly financed by the Usher Syndrome Foundation and partially co-financed by Usher Syndrome Ireland. If this study produces any positive results, the study of tears may lead to new strategies in USH research.

Tears
Tears are human body fluids. Tears are rich of proteins, lipoproteins and exosomes. Exosomes are small bladders which contain a wide range of molecules inside like RNA molecules. Thanks to that, exosomes are important for the communication between cells. In addition, they can be isolated from tears, which allow the study of their content.
As tears can be collected in a non-invasive way (without entering the body) from patients, they allow for easy and patient-friendly isolation of exosomes.

New biomarker for research
Biomarkers are measurable indicators that may indicate that someone is ill, predict how serious the illness will be or show whether a treatment is effective or not.

By making use of tears, the researcher Dr. Irene Vázquez Domínguez wants to find out whether biomarkers can be found that may be used to improve the diagnostics and to better predict the development of Usher Syndrome type 1b. In the long term, point-of-care tests could be developed on the basis of these biomarkers. Point-of-care tests offer care professionals the possibility to start, monitor or adjust a future development.

The MYO7A geneWe know that more than 10 genes are involved in Usher Syndrome.
This new study is focused on one of these genes, being the MYO7A gene. This gene is responsible for the production of a specific protein: Myosin, which keeps the photoreceptors (the rods and cones) of the retina alive.

Some children having mutations in the MYO7A gene do not develop retinitis pigmentosa in their childhood and puberty beside their hereditary deafness. Here we speak of non-syndromic deafness 

How can this be explained and/or predicted? The answer to this question may lead to better diagnostics. Sometimes it is really difficult for the parents to cope with the uncertainty whether or not their child will develop retinitis pigmentosa (RP).

Increasing the present knowledge about the MYO7A gene is necessary for finding new biomarkers that can be used for making the diagnosis and for predicting the development. At the same time, this knowledge can also be used in monitoring after a treatment.

Isolation of exosomes
Usher Syndrome falls within the group of Retinal Dystrophy diseases (RDs). The deterioration of the eyesight is caused by the dying of retinal cells, such as the light-sensitive photoreceptors and/or the retinal pigment epithelium (RPE).
Within the retina RPE cells are responsible for the majority of the production of exosomes. Previous studies indicated that tears may be rich of RPE exosomes.

The goal of the study is to isolate exosomes from tears as well as from RPE cells. Then, the content of both will be studied. First, the control group will be compared with the material from USH1b patients. Then the information from tear derived exosomes and RPE derived exosomes will be also compared to assess if, as it was suggested before, they provide the same information. If this turns out to be successful, this study will show that exosomes can be used as a means to develop new strategies in USH research.
Finally, this study will also show whether tears can be a source for research. This would help to find an easy and patient-friendly way to isolate exosomes.

This one year study was budgeted at  € 75.000, -.
Stichting Ushersyndroom (Dutch Usher syndrome Foundation) will finance this study with co-financing from Usher Syndrome Ireland.

 

Watch the powerpoint presentation by
Dr. Irene Vázquez Domínguez 

Ivonne Bressers has appointed a knight of the Order of Oranje-Nassau.

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Mayor Ahmed Marcouch and Ivonne Bressers

King Willem-Alexander has appointed Ivonne Bressers (57) a knight of the Order of Oranje-Nassau. As president of the Dutch Usher syndrome Foundation and the driving force behind it, she is of inestimable value to the Usher patient group. Mayor Marcouch presented the award during the “lintjesregen” at the City Hall in Arnhem.

Ivonne Bressers has Usher syndrome. Most people with this very rare disorder are born hearing impaired or deaf and experience progressive sight and hearing loss. There are 400,000 patients worldwide, including 1,000 in the Netherlands who suffer from Usher syndrome. There is currently no treatment to stop the process of becoming deaf and blind. Ivonne’s deepest wish is that in 2025 there will be a treatment for every Usher syndrome patient.

Ambitious volunteer
From 2009 to 2015, Ivonne volunteered tirelessly and unpaid for the interests of the deafblind patient group. She participates as a volunteer in various working groups of the Eye Association OOG & OOR and makes great strides. With her project group, she managed to ensure that the second cochlear implant (an implanted hearing prosthesis) for deafblind people is fully reimbursed by health insurers. She also initiated the establishment of a national expertise center for patients with Usher syndrome within the Radboudumc. Nowadays, these patients can come here with their specific care needs.

Usher syndrome Foundation
In 2015 Ivonne starts in the campaign team of the Dutch Usher syndrome Foundation and joins as general board member in 2016. In 2019, she is appointed president of the foundation. A task she performs with enthusiasm, dedication and vigor.

From its inception until now, Ivonne, together with the efforts of volunteers for the Foundation, has managed to raise more than 1.1 million euros. The funds received are used to finance very promising scientific research, both at home and abroad, into an effective treatment for people with Usher syndrome.

The Royal Decoration is an extra stimulus for Ivonne to keep working on fulfilling her deepest wish: “in 2025 Ushersyndrome will be treatable for everyone”.

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New type of Usher Syndrome discovered: USH IV   

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The team of the Hearing & Genes Expert Centre of Radboudumc lately made a discovery: Usher Syndrome includes four different clinical types. The researchers, with Hedwig Velde as principal author, recently published their study and findings in the leading Human Genetics. With the identification of minor faults (mutations) in the ARSG gene and the description of a new clinical picture, they confirm the discovery of a fourth type of Usher Syndrome. 

This really is an important discovery, which gives more clarity about a number of patients with atypical Usher complaints without a genetic diagnosis. In the meantime, following the identification of ARSG as Usher gene, globally fifteen people have still been diagnosed, now that they all appear to have mutations in the ARSG gene. As it has been demonstrated that these patients have a common pattern of symptoms, this is no longer an atypical picture, but it makes up a new clinical type.       

A patient with an atypical clinical picture
Very rarely a patients visits the outpatients’ clinic showing symptoms that correspond with the clinical picture of Usher Syndrome (loss of hearing combined with retinitis pigmentosa), but which picture deviates from the familiar Usher types. This is called an atypical clinical picture. In some cases no generic cause is found in the Usher genes that are known so far. Consequentially, these patients are unfortunately sent home again without having been diagnosed (and without any clarity). 

Hedwig velde

 Hedwig Velde is researcher and doctoral candidate at the ENT section Hearing & Genes of the Radboudumc. She is studying patients who suffer from loss of hearing but who have not been genetically diagnosed. With her research team she confirmed a new Usher Syndrome type, which is caused by minor faults in the ARSG gene.  

A publication from the year 2018 written by a group of scientists in Israel described the discovery of the ARSG gene with Arylsulfatase G as a protein that might be involved with Usher Syndrome. The researchers from Israel described five persons from three families who all had the same minor fault in the ARSG gene. Such a publication may give other researchers ideas for their studies.  

Studying the DNA of several people within one family sharing the same symptoms is a big help for scientists. Hedwig Velde: “There is a big chance that all patients within the family share the same genetic cause. When outside the family that has been studied another patient is found with the same atypical clinical picture and a minor fault in the same gene, this may confirm the relation between the gene and the clinical picture. Of course, the chance of coming across this patient is really small. Usher Syndrome is very rare.”  

Until the national Expert Centre in the Radboud UMC saw a patient with this atypical clinical picture of Usher Syndrome and Hedwig Velde and other researchers in the Radboud UMC continued the study that was started by the team in Israel in 2018.    

New type now confirmed
With the publication of Hedwig Velde c.s. the researchers confirmed this new type. The researchers found minor faults in the same gene (the ARSG gene), which creates the codes for the Arylsulfatase G protein. This protein is involved in the degradation of another protein and the idea is that malfunctioning of Arylsulfatase G will lead to an adverse accumulation of the protein that normally should be destroyed. With this study the research team also demonstrated that the minor faults in the ARSG gene that have been found really result in a non-functioning protein.  

The clinical picture of the type does not fit in with the already known Usher types I, II and III. Apart from a later starting age of both the loss of hearing and the retinitis pigmentosa, the ophthalmic defects are more centrally located. This means that the vision problems with these patients rather occur in the central part of the field of vision as opposed to the other Usher types, which usually show problems in the outer part of the field of vision (the periphery). As the clinical picture is consistent with all USH IV patients, researchers of the Radboud UMC are of the opinion that this is not atypical Usher, but a new clinical type: Usher Syndrome type 4.   

Hedwig: “By publishing these findings, we as researchers hope to start up a discussion in the scientific world. Various studies may together lead to the confirmation that the findings are correct or, in some cases, rebut these findings. In case of USH IV it is the accumulation of evidence in several publications that enables us to confirm that this clinical type really is a new Usher type.”    

By now, globally several patients have been diagnosed for this Usher Syndrome type and for minor faults in the same ARSG gene. Previously, these patients used to be categorised in the group ‘diagnosis unknown with atypical Usher symptoms’.    

The course of Usher Syndrome type IV
Both the loss of hearing and the complaints related to retinitis pigmentosa start at a later age with people suffering from USH IV. Patients started to develop complaints concerning hardness of hearing between the ages of 20 and 40 and the retinitis pigmentosa between the ages of 40 and 60. Based on the audiograms of USH IV patients, the research team has been able to calculate that the loss of hearing starts about the age of 17.  

The course and the progressiveness are not necessarily milder than with the other Usher types. “We still have little insight into the course of USH IV, because only fifteen patients have been described and we therefore have to base our findings on this small group.” 

Genetic tests or not?
With this discovery the researchers of the Radboudumc have managed to fit in yet another piece of the ‘Usher puzzle’.” Thanks to this, a part of the patients with an unknown diagnosis will eventually be given clarity and this is really important to this group of patients.  

Unfortunately, there still are people for whom the Usher-related symptoms cannot be confirmed by a diagnosis. This makes genetic tests so important!    

The physicians indicate that, of course, the choice is still to be made by the patient. One patient attaches a lot of value to a confirmation by means of genetic tests, while another does not.  
Hedwig: “There are various reasons to have genetic tests done or not. An advantage of a genetic diagnosis is that with this the development of a disorder can better be predicted and that this may help the patient to adapt to the situation. Imagine that you are hard of hearing at a young age and that there is a small chance of becoming visually impaired. However, if you know that you will be visually impaired, then you had better concentrate on the kind of care that will help you both early and later in life. For instance, in this case learning sign language will not be a long-term solution for your loss of hearing, but good hearing aids may make a substantial contribution.”  

Genetic tests will also help the scientific world to get further. For example, as scientific research allows for comparing the DNA of various patients, new genetic causes can be discovered. Besides, this offers a possibility for meticulously mapping out the relation between a minor fault in a gene and the corresponding complaints.
Hedwig: “Because of this, future patients can be better informed about their diagnoses. On the other hand, it is also important for any future genetic treatments to know the exact underlying deviations in the DNA.”    

Usher Syndrome: 4 types and 11 genes involved
In 2022, type IV and the ARSG gene will be added to the list of Usher types and genes involved in the development of Usher Syndrome. So at this moment, Usher Syndrome distinguishes 4 types with 11 different genes involved. [Ed.: This evidence is not entirely conclusive for USH1J (CIB2) yet]
For all these genes scientific evidence has been provided that minor faults (mutations) in these genes will result in Usher Syndrome.    

The Knowledge Portal of the Usher Syndrome Foundation provides a complete overview of the genes with the names of the ‘protein involved’.     

Here you can read the publication of the article by Hedwig Velde c.s. in Human Genetics.  

 

Run4Usher Zandvoort breaks all records!

LEES ARTIKEL IN HET NEDERLANDS

On the 27th of March, the Run4Usher team joined almost 12.000 other runners at the start of the Zandvoort Circuit Run. This beautiful spring day set the scene for one of the first major running events of the year. The Ushers Syndrome Foundation was chosen by Rotary Zandvoort as the official charity for this edition of the Zandvoort Circuit Run. Not only adults appeared at the start; for the young participants there was also a special Kids Run. The large team of Run4Usher broke all records on this wonderful day and collected the fantastic amount of € 85.427,- !

Pole Position
From Pole Position, the 185 participants of Run4Usher started the 13th edition of this spectacular running event.  The program consisted of various courses: the 10 English Mile (16.1 km), 12 km and 4 km (One Lap) and for the youngest participants there was the special Kids Circuit Run and the Wheelers and Racerunner Race. Also Carol Brill and Debs Heffernan from Usher Syndrome Ireland had been specially flown in for a one-lap track over the circuit.

In the special tent of Run4Usher at the Paddock there was the opportunity to meet each other and share the solidarity. After the Kids Circuit Run, the young participants were treated to various activities led by a large group of volunteers, there was candy floss, face painting and costumes as well as go-kart races at the Paddock.

Rijsterbij
The rapper Rijsterbij (Martijn Rijsenbrij) gave a benefit concert, selling his CDs and donating the proceeds to Stichting Ushersyndroom. Martijn Rijsenbrij sings Dutch hip-hop with solid beats. “It’s getting dark, all the lights are going out, but I’m not going to wait for the day it gets dark, to that thought I say thunder”. Martijn has the eye disease Retinitis Pigmentosa, just like all people with Usher syndrome.

All records broken
The participation and presence of the Run4Usher team did not go unnoticed and generated a lot of attention for Ushersyndrome during the event and in the media.

The proceeds for the Ushersyndrome Foundation are a record: the runners and their supporters, the volunteers who collected at the event and the additional proceeds from LeChampion and Rotary Zandvoort together raised € 85.327,- !

A long haul
For the project group, the organisation has also been a challenging time. The team that organised this edition of Run4Usher consisted of ‘Ushers’ Machteld Cossee and Carin de Bruin and ‘Usher parents’ Daan Wijsbek, Esmé Ter Stege and Liesbeth Kenters. Machteld: “I remember that in mid 2019 the first contact was made with the Rotary Club and Le Champion. We were going to watch and gain experience at Stichting Hartekind, which had been chosen as the Charity for that year, but unfortunately the pandemic threw a spanner in the works.”
Despite this, the project group continued to make plans and recorded a promo with John Williams, a Dutch celebrity. Because you never know!
Unfortunately, the 2021 edition of the Zandvoort Circuit Run was also cancelled due to corona.

Until the end of 2021, event organisation Le Champion cautiously gave the go-ahead.
“We had to switch gears for a moment and suddenly we were back in business. It took a lot of Zoom meetings and group apps to get everything right,” say parents Daan and Esmé. “Various interviews, sending out newsletters and having to arrange all the practical matters at the last minute, it was simply top-class sport! according to Carin. The ever-calm Liesbeth thinks it has been a matter of long breath. “We did it, and we did it well”. Fortunately, the project group was able to count on the support and assistance of a huge group of volunteers for the practical help.

Record proceeds
Thanks to sponsorships from runners, the sale of merchandise and volunteers who collected during the event, they managed to raise a staggering € 65.427,- !
On 11 April last, the members of the project group received a cheque from the Rotary Zandvoort and event organisation Le Champion.
This brings the total record revenue of € 85.327,- !

Thanks to the financial support of “Stichting ter verbetering van het lot der Blinden” for the incurred expenses, the entire proceeds of Run4Usher Zandvoort Circuit Run can benefit scientific research into and treatment of Usher, in order to stop the process of becoming deaf and blind. In this way, the dot on the horizon for people with Usher syndrome is coming ever closer.

Here you can see all the photos of the Run4Usher edition Zandvoort Circuit. With many thanks to photographer Sanne ter Horst.

Click me

Would you like to be part of the Run4Usher team? Or would you like to help organize the next Run4Usher edition during the Seven Hills Run (19 and 20 November) in Nijmegen? Then please contact us via the mail run4usher@ushersyndroom.nl

Moon-Rocket Grant

Usher Syndrome Foundation Grant Call:
The Moon-Rocket Grant

The use of the word ‘Ushers’ for people with Usher syndrome is meant with a wink and refers to the meaning of the English word ‘Ushers’. People with Usher syndrome are the messengers of an important story or message.

The ‘Ushers’ tell what they need, what kind of help they need, what they find important and how they experience their life with Usher syndrome.

Currently, there is no treatment available for 400.000 ‘Ushers’ in the world. What is needed for the ‘Ushers’ is more knowledge and research into the Usher Syndrome. That is why Stichting Ushersyndroom [Dutch Usher Syndrome Foundation] awards the Moon-Rocked Grant: € 100,000 for research into Usher Syndrome.

The Moon-Rocket Grant
The goal of the Moon-Rocket Grant of the Usher Syndrome Foundation is to realize our formulated moonshot: “a cure for Usher in 2025!”.

The Moon-Rocket Grant is intended to financially support research into Usher Syndrome (any form or subtype).
All research proposals submitted must fit into one of the four core values ​​the Usher Syndrome Foundation has defined by:

  • Treatment
  • Understanding
  • Diagnostics
  • Impact

The Moon-Rocket Grant will award a maximum of €100,000 per research. If there are several eligible projects, more projects can be funded. A maximum of € 200,000 is available for financing.

For more information click on the buttons below.

MOON-ROCKET GRANT FLYER GRANT CALL APPLICATION FORM

Do you have any questions or would you like to receive the application form in Word version? Mail to research@ushersyndroom.nl

1 million euro

What has Stichting Ushersyndroom [Dutch Usher syndrome Foundation] done with it?

We provide an overview and a glimpse into the future.

Mini genes USH2A
In the ‘mini genes’ project, the USH2A gene is artificially made smaller by taking specific parts of the gene and sticking these together (= minigene). This suddenly 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.
The Stichting Ushersyndroom finances this study in 2016.

Read more ….

CRUSH study
The expertise centre for Usher Syndrome in Radboudumc started in 2019 a natural development study into Usher Syndrome, de CRUSH study.
This is a very important step in the research into a treatment for Usher Syndrome, because this study may substantially shorten the running time for trials. Stichting Ushersyndroom finances this five-year study.

Read more …

Mini genes USH2C

In 2019, the Usher Syndrome Foundation funded the new research into Minigenes for USH2c. USH2c is caused by mutations in the USH2c gene (ADGRV1), and these errors in the gene lead to a progressive form of hereditary deafblindness. However, this gene is very large, so researchers want to try to make an artificially shortened version of the ADGRV1 gene. These mini-genes will be small enough to fit into a ‘viral vector’, but at the same time they must also remain functional.

Read more …

Knowledge portal Usher syndrome

The Usher Syndrome knowledge portal is made available by Stichting Ushersyndroom.
A portal that has been developed for and by people with Usher syndrome in which they have bundled all their knowledge and information as experience experts and ‘Usher experts’.

Read more ….

Sleeping research
Are patients suffering from Usher Syndrome so tired because of the huge efforts made in connection with their poor hearing and eyesight or is something else going on? Researchers in the Radboudumc try to find an answers to this question. There are indications that perhaps there is more going on, a genetic cause.
In summer of 2021, the research into ‘The recognition of sleeping problems with patients with the USH2A gene’ stared. Stichting Ushersyndroom will finance a large part of this study.

Read moe ….

Database USHIII

This year in 2021, the North-American foundation Usher III Initiative has taken preliminary steps towards collecting the information necessary to establish the first comprehensive global USH3 patient database. This resource will be critical to the design of future clinical trials and will significantly advance knowledge of the disease and its impact on patients.
Stichting Ushersyndroom has committed to making a contribution to support this effort.

Read more ….

Extra large vectors on mini retinas

Stichting Ushersyndroom is funding the majority of the new research “Genetic drugs preventing blindness due to loss of USH2A function” which has recently started. The research team led by Jan Wijnholds, who works at the Leiden University Medical Center (LUMC), will test two treatment methods on ‘mini-retinas’ made from human stem cells. The researchers want to determine if the light sensitive cells in the mini-retinas can be activated by the light-sensitive cells after administration of gene therapy.

Read more ……

The dot om the horizon

The mission of the Stichting Ushersyndroom is: “In 2025, Usher Syndrome will be treatable!” This is the all-encompassing goal, the “moonshot”, from which everything else is derived. This is why Stichting Ushersyndroom is here.

  • At the beginning of 2022, Stichting Ushersyndroom will send out a call: The Moon Rocket Grant. Researchers worldwide can submit an application for a grant that contributes to the mission ofStichting Ushersyndroom: “Usher Syndrome will be treatable by 2025!”.
  • A patient brochure is in the works and will be released in early 2022. It will be available online and offline.
  • In 2022 we will start with the first webinar. This is accessible to everyone who is committed to the mission of the Stichting Ushersyndroom. A new webinar with a different speaker every quarter.
  • Of course we also want to send out a new call: Rocket Fuel Grant. And the desire to be able to subsidize even more research projects that can lead to a solution for all people with Usher syndrome.

We are well on our way to the dot on the horizon! However, a lot of money is still needed. Can we count on your support again in the coming years?

Do you have any questions or do you want to support the foundation? Send an email to info@ushersyndroom.nl

DONATE

What would you do with one million euros?

By Nico de Milliano, Chairman of the Advisory Board of Stichting Ushersyndroom [Dutch Usher syndrome Foundation]

Stichting Ushersyndroom will soon reach a wonderful milestone: the first million will be brought in even before the end of the year. And we want to celebrate this!

What is Usher Syndrome?
Usher Syndrome is a rare hereditary disorder. The children suffering from this disorder are born deaf or hard of hearing and-they will also experience a progressive loss of eyesight. Eventually, people suffering from Usher Syndrome become both deaf and blind. About 1000 people in Netherlands suffer from this syndrome.

What is Stichting Ushersyndroom?
An active group of people who are suffering from Usher Syndrome themselves or who are partner, parent or friend of someone suffering from Usher Syndrome. Stichting Ushersyndroom has existed for about six years and its mission has been formulated as: ‘A treatment for Usher Syndrome in 2025’.

In order to reach this goal, the Usher Syndrome Foundation is committed to making the syndrome more widely known, to bringing people suffering from Usher Syndrome together and to being active in fundraising.

The foundation closely works together with similar organisations abroad, such as the US, Ireland and the UK and it has good contacts with research centres all over the world.

What is money needed for?
Most of all, money is needed to finance research. As this is about a rare disorder, governments and businesses want to spend no or little money on research.

Usher Syndrome is a genetic disorder. In recent years, large steps have been taken in research that are to lead to treatment methods. The mission of the foundation is realistic, but a lot of money will be required in the coming years.

What are we going to do with one million euros?
Stichting Ushersyndroom  is really happy that we have been able to collect such a large amount of money within a few years. Thanks and honour to all those who, with large and small campaigns, have achieved this.

The money will be used for various research projects in the Netherlands and abroad. We will mention a few:

  • A study into the natural development by the Expert Centre for Usher Syndrome in Radboudumc Nijmegen, the Netherlands, will receive an amount of € 257,000 in the period 2019-2024;
  • We make a contribution of € 10,000 to setting up a database for Usher-III patients in the US;
  • We co-finance a study into sleeping problems experienced by people suffering from Usher Syndrome.

The work has not been done yet!!
Research is a long-winded matter. Therefore more money will be needed in the years to come.
Therefore, the Stichting Ushersyndroom will keep working really hard to fulfil its mission.

Let’s go for two million!

Read also:
What has Stichting Ushersyndroom done with one million euros? Here take a look at the complete overview.