If you slowly become become deaf and blind

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Source: Gezondheidsnet [Health net] and NU.nl

How is Machteld Cossee doing today?


Overwhelmed with reactions
The film moved people from Machteld’s wide social circle as well as other viewers Director Hetty called the number of reactions to the documentary ‘overwhelming’. Machteld continues: ‘People around me know that I suffer from Usher, but the film zooms in on this. It shows the rough side of Usher.’ She confesses that she did not pick up the children from school herself the first four days after the broadcast. ‘When I appeared in the schoolyard again, other parents came to me. They offered their help and said they now had a better understanding of what was going on. How often was I called ‘arrogant’ or ‘a muddlehead’? I would never call myself that. The film gave people more insight.’ Hetty adds: ‘People looking at Machteld from a distance don’t have any idea how much difficulties she continuously has to overcome. I saw her on a photo with her husband Lars on the tandem in the JAN and I immediately knew that I wanted to watch at things along with her.’

The film did not only have influence on Machteld’s environment but on that of her fellow sufferers as well. ‘Six months ago, a woman I didn’t know came at my door. She stammered a bit while she was standing there and I really had no idea why she had come. Her son appeared to suffer from Usher. When she saw me walking one time, she mustered up her courage and rang at my door. In the period after that we had coffee together twice to talk about this.’ Actually, Machteld has become a kind of standard bearer. ‘Usher Syndrome Foundation received a lot of reactions after the broadcast and various young people had their “coming-out” as I call this after the film.’

Put things into perspective because of Usher
Hetty Nietsch made the film with her daughter Lisa Bom. ‘She had just finished the academy of arts. Working on a film for a few years really costs a lot of money, so we took a small camera and started to work with the two of us. The cameras became better in the course of the time.’ Lisa sometimes even slept at the home of Machteld and Lars.

Source: NPO 2Doc.nl
Text: Wieneke van Koppen
Photo: Lin Woldendorp

CRUSH study and database for unraveling Usher Syndrome

Usher Syndrome
Usher Syndrome is a rare hereditary disease. Children suffering from Usher Syndrome are born deaf or hard of hearing and they will also develop a visual impairment from their teenage years. This starts with night-blindness and an ever narrowing field of vision, like looking through a straw. Usher Syndrome eventually leads to deafblindness. Sometimes imbalance problems are also involved. The diagnosis has a great impact on the perspective. There is no treatment yet, but there are promising developments worldwide.

Developments in scientific research
Join the CRUSH databaseAt this moment, an increasing number of centres around the world are busy developing a treatment for the various types of Usher Syndrome (Usher 1b, 1c, 2a, 2d and 3) aimed at inhibiting or stopping the deterioration of vision and hearing. The Radboudumc particularly puts the emphasis on this kind of research on Usher Syndrome type 2a, the most common type of Usher Syndrome that is caused by mutations in the USH2A gene. This gene contains the code for the usherin protein, which plays an important role in the eye and the ear. One of the (gene) therapeutic studies that is conducted is the exon-skipping method. Here one of the coding exons (informative parts of the gene) is removed from the gene and ‘covered’ by a so-called ‘genetic patch’. This results in a shorter but possibly also more functional usherin protein in the retina, by which the deterioration of the eyesight will be stopped or slowed down. Recently, the pharmaceutical company ProQR announced that it will start the first phase 1/2 trials for mutations in the exon 13 at the end of the year 2018. . See ‘ProQR will be start with first trials Ushersyndrome 2a’
In order to be able to test the effectiveness of this type of medicine in clinical trials, it is important to have a clear picture of the natural development of the disease.
However, the exon-skipping method is not suitable for all types of Usher Syndrome and it will take a lot more research to find solutions for all Usher patients. Still, the first important breakthroughs in research are made now!

Ronald Pennings, ENT specialist at Radboudumc Nijmegen (the Netherlands):
“The eventual goal of the Expertise Centre for Usher Syndrome is to be globally leading in the development of (gene) therapy for Usher Syndrome.”

Usher Syndrome Expertise Centre
Dr. Ronald Pennings is recently received the prestigious title ‘Principal Clinician’. With this he wants to set up a trial centre for medicinal treatment of patients with hereditary loss of hearing, including Usher Syndrome, within Radboudumc. Prof. Carel Hoyng is as ophthalmologist of the Radboudumc also directly involved in the care for and research into Usher Syndrome. Additionally, he leads the trial centre of the Ophthalmology department, which is studying retina degeneration by means of testing new medicines. Hoyng and Pennings together lead the Expertise Centre for Usher Syndrome. “The eventual goal of the Expertise Centre for Usher Syndrome is to be globally leading in the development of (gene) therapy for Usher Syndrome. Not only the developments in the laboratory of Erwin van Wijk, but also detailed examination of the natural development of Usher Syndrome with as many people as possible will enable us to obtain this position”, according to Ronald Pennings.

CRUSH study and a CRUSH database
The CRUSH study will map out and analyse the natural development of the progressive disease Usher Syndrome with 50 patients for a period of five years.
The protocol of this study is in line with the first international natural development study, the RUSH2A study of Prof. Duncan in California, with makes exchange of data possible.
Apart from the CRUSH study, an (international) accessible CRUSH database will be set up in the Radboudumc as well for properly recording the results of the examinations.
The CRUSH database is a collection of various clinical data, including audiograms, field of vision examinations and DNA results. In this way the prognosis can be better recorded and a possible explanation for the large individual differences in loss of hearing and eyesight between patients, even of the same family, can be found. This CRUSH database will be accessible for other centres, so they can store their data in the database as well.
Most patients are already known in the national RD5000 database, but this database only contains personal data and the diagnosis. The Radboudumc works together with the physicians and researchers working with the RD5000 database. The CRUSH database, in which the clinical data of patients are stored as well, is intended for all people who have been diagnosed with Usher Syndrome. Researchers of the CRUSH study will select patients from the CRUSH database who meet the criteria and then invite them to participate in the CRUSH study. You can register for the CRUSH database by sending an e-mail to ushersyndroom@radboudumc.nl

Stichting Ushersyndroom, Ronald Pennings (ENT specialist) and Carel Hoyng (ophthalmologist) of the Radboudumc advise all patients suffering from Usher Syndrome to compose their own files, making sure that the data will quickly be known when registering for the CRUSH database. See ‘Start setting up your own patient file!’

‘CRUSH USH’
Annouk van Nunen, secretary of Stichting Ushersyndroom and patient herself is happy with the start of the CRUSH study and the CRUSH database. “At this moment there are many families within which several children are affected by Usher Syndrome. However, even between brothers and sisters there are major individual differences in the level of deterioration of eyesight or hearing. If it is known which external factors may influence the deterioration of eyesight and hearing, patients can timely anticipate and make a contribution to slowing down the deterioration themselves. Everyone participating in the CRUSH database makes a contribution to finding the solution. As soon as the CRUSH study has been started, the focus will be shifted towards the acquisition of more funding, so as to make it possible to follow more patients suffering from other types of Usher Syndrome in detail in the future in a study. All patients (young and old, type 1, 2 or 3) play crucial roles in the eventual unraveling of Usher Syndrome.”

In short, the CRUSH study and the CRUSH database are in the interest of all people diagnosed with Usher Syndrome. This is the only way to unravel the disease more quickly and to substantially shorten future trials in the Netherlands or elsewhere in the world.
The full financing of the CRUSH study is guaranteed by Stichting Ushersyndroom for a period of five years, also thanks to the donors and the co-financing of the Dutch Dr. Vaillantfonds and Oogfonds. #CRUSH4all

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

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

Stichting Ushersyndroom finances CRUSH study

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

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

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

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

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

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

Run in pace, following a pacer

With a simple gymnastics band, Usher patient Ivonne Bressers (51) from Arnhem keeps direct contact with her buddy, Edith Mulder during the 7 Hills Run.
Mulder: ‘If necessary, I call “high” to let Ivonne know that she has to lift up her knees a bit higher for, for instance, a threshold. Or I call “right” or “left” when we have to go around a hole or a puddle. I love doing this. Everykilometre is exciting, but really beautiful too!’

Out of the 35,000 participants of the 7 Hills Run held on 19 November, 144 people ran in the Run4Usher team to collect money for research for the benefit of people suffering from Usher Syndrome. This hereditary disease can lead to full deafness as well as blindness. In this fourth year of their participation in the running event, the number of participants was doubled and at this moment twice as much money has been collected as well. Apart from runners without an impairment there also is a small number of people with an impairment, like Bressers.

About 1.5 metre before and after Bressers and Mulder three ‘pacers’ are running, who keep the path clear for a total of seven badly hearing and seeing runners of the Run4Usher team. Bressers: ‘I thoroughly enjoy this. Because of my impairments everything goes slowly in my life. When running, I can give myself a free rein. Besides, we enjoy each other’s company.’ Bressers fully trusts her buddy and the pacers.
‘This was my first 7 Hills Run and it went very well. Fortunately, it was only raining exactly before and after the run. One time someone was grumbling about the pacers until she saw who we were and she excused herself a thousand times.’ Bressers was very satisfied with the wonderful route along the hills.

Annouk van Nunen (41) from Leiden also ran with her permanent buddy, Leen Ooms. Ooms thinks it is great to be able to offer blind and visually impaired people this experience. ‘It is a really responsible task. People cannot see straight away that people with an impairment are running here. Especially not at a crowded event like this. The runners and their buddies are running widely and therefore have to pass widely. Sometimes we really have to elbow our way through the crowd, when necessary with a lot of noise, to clear the way for our runners.’

Four people suffering from Usher Syndrome also ran the 7 Hills Night. This was extra difficult because of their night-blindness. The disease is progressive and shows itself in a lot of variations. It often begins with being hard of hearing until night-blindness is developed in puberty and later tunnel vision. Bressers: ‘It is like she is looking through a straw. I cannot see anything outside that central point. For my hearing I now have implants, but there is no remedy yet for the blindness. I really hope more research will be done soon. The solutions may also be applicable to other eye disorders.’
The woman from Arnhem finds it hard to be forced to accept the growing loss of two senses. ‘The possibilities to compensate the one impairment with the other are decreasing as well. Still, I try to find a balance between asking for help and being independent over and over again. Fortunately, more and more actions are organised and Usher Syndrome is becoming increasingly widely known.’

Source: De Gelderlander, Nijmegen e.o.
By: Loes Wijffels
Photo: Gerard Verschooten

‘I do not see myself as a person with restrictions. I am just Jeff.’

He was born deaf. And he will be blind as well. Jeff Horsten sings a self-written song about his restrictions on YouTube. The 23 years old man from Waspik, the Netherlands, suffers from Usher Syndrome, a very rare disorder. Still, Jeff surprises the people around him with his laughter, his creativity and his optimism. ‘I want to inspire people. I do not see myself as a person with restrictions. I am just Jeff.’ The film of his song ‘Welkom in mijn wereldje’ [Welcome to my small world] has been watched thousands of times and dozens of people have shared it on Facebook. The film was put on-line a couple of weeks ago. ‘Tears’, ‘respect’ and ‘goosebumps’ are responses to the touching song.

Not alone
‘I want to show other people suffering from Usher Syndrome that they are not alone’, says Jeff. He sings the song together with singer Jorien Habing. The text is about the ‘tunnel’, as the man from Waspik experiences his life. It refers to his deafness and poor eyesight: Jeff looks through two holes of half a centimetre in diameter. ‘People usually can see 180 degrees.’ When Jeff looks at someone, he must move along his head. His eyesight is blurred: now 50 to 60 percent. Jeff will eventually become blind. With the help of his friend, Joep Rijk, Jeff had the song recorded in the Swamp studio in Raamsdonk. The idea came up in rehabilitation centre Het Loo Erf in Apeldoorn, where Jeff has spent nine months by now. He hated music for years. Just because he could not hear it. “One moment I heard Ring of Fire by Johnny Cash. I managed to listen to the rhythm. Later I started to experiment with music. I sometimes take a guitar and play a little. However, it remains difficult because I cannot listen well myself.’ Jeff has plenty of texts. He writes a lot. ‘Writing is my way of release. It provides a means to express myself. As a teenager I often picked up the pen. It was a kind of game to me. Suddenly all emotions are lost.’ Jeff’s parents think that the song is really confrontational. Father Pierre: ‘I listened to the first lines but I let the rest of the song rest for a few days.’ ‘Of course, this is not new to us, but many tears were wept in our house when we heard the song’, according to mother Marja. Jeff’s parents experience their lives as a struggle for their son. To get him to the right school, to give him the proper guidance. His poor eyesight was discovered only after seven years. ‘As a boy, Jeff often had quarrels. I was at school almost every day to stick up for Jeff. Now we know that he could not express himself. He felt misunderstood.’

Clicks
Jeff often stumbled over things, he became night-blind and fell over other children while playing. Marja and Pierre later heard in the Radboud Hospital in Nijmegen that Jeff suffers from Usher Syndrome. ‘We had looked up a lot of things on the Internet. Then everything clicked. We were quite sure about it. When then things are actually confirmed, the world stops turning.’
It is hard to accept that Jeff’s restrictions are increasing. He cannot participate in things that are self-evident for other people of his age. Marja: ‘Like riding a bike or a moped. Jeff loves cars, but he will never be able to drive one.’

I am always mentally tired.
I seem to get up with an energy level of 10 percent.

‘It is putting up with things again and again’, Jeff describes the setbacks. His resilience has grown in the course of the time. ‘I give things a place and I have become more flexible. Now I can say “I cannot do it”. I have no choice. In the past, I was only surviving. Now this has been changed into living. I am living. I have switched over.’ Thanks to a cochlear implant he can follow conversations fairly well. He can also talk. His voice is not really bright, because he missed sounds in his early childhood. Jeff manages to follow an education at the Prinsentuin College in Andel and is a qualified animal carer. Jeff can enjoy things, such as Johnny Cash, films of cars on YouTube and the dog that he hopes to have soon. However, despite his humour and positivism, Jeff is struggling with his feelings. ‘I have my difficult moments. Sometimes these last for a day. Then I withdraw into myself and I want to be alone. I do not want other people to see me like this. Shit happens. Everything has its price and I have to pay mine.’ At this moment, the man from Waspik is going through the last phase of his rehabilitation. Jeff is prepared to becoming blind at Het Loo Erf. It is still uncertain when this will happen. ‘I do not notice any major changes between one day and the next. It goes in tiny little steps.’ The man from Waspik is teaching himself some practical things, such as doing the laundry, cooking, shopping or read Braille. ‘Only 10 percent is about the restriction, whereas 90 percent of the rehabilitation is about mentality. They give me self-confidence. I can do much more than I think.’ Marja: “I am surprised about how cheerful everyone is at Het Loo Erf. Its; incredible. We can learn a lot from them.’ Jeff nuances: “In our tiny world there is no place for grey, as many people experience days in their lives. We are either happy or sad.’ His tunnel vision costs really a lot of energy. ‘The greatest problem is the fatigue. I am always mentally tired. It feels like I get up with an energy level of 10 percent. When I do something for a few hours, I have to go to bed. I have to prevent getting a burnout.’ When Jeff is ready with his rehabilitation, he has to take a big step. He will go and live by himself. In the centre of Waalwijk. 100 percent independent. ‘I do not want to live under supervision. Never. My parents are helping me really a lot. They do everything.’ Jeff will probably move house next year. This will be another difficult moment for the Horsten family. ‘We are afraid of the loneliness. This is our major concern’, Marja says. Jeff: ‘I am not easily frightened. I know this will be a struggle, but I have had to fight for everything in my life. I am convinced I will manage.’ His mother endorses this: ‘It has cost a lot of energy. Still we look ahead with a positive mind. We have already struggled, struggled and struggled for 23 years …’

Watch and listen to ‘Welkom in dit wereldje’

Source: Brabants Dagblad
By: Sjoerd Marcelissen

‘Sheer happiness’: Liesbeth is becoming blind and deaf and wants to keep seeing her children

Liesbeth Beekhuis (35) suffers from Usher Syndrome and will slowly but surely become both deaf and blind. In ‘Sheer Happiness’ she is surprised with precious memories that she can save for the future.

Liesbeth is overwhelmed by emotions when she sees what Ruben Nicolai and his team have arranged for her.

SLOWLY BOTH DEAF AND BLIND
Liesbeth is happily married and mother of two wonderful children of six and two years old. However, her picture of the future has been dark since the moment that she was told that she suffers from Usher Syndrome. As a result of this disease, her eyesight has been bad already for a while and this will only get worse over the years. There is a big chance that she will be both deaf and blind at a certain moment.

LIESBETH WANTS TO SEE HER CHILDREN
Her greatest fear is that she will not see her children as adults. In Sheer Happiness the new host Ruben Nicolai helps her to build up precious memories for later times. In this way, Liesbeth tries to save the important moments of her life in her memory in order to be able to retrieve them when she has completely lost her eyesight.

LOOK INTO THE FUTURE
Ruben has a great present for Liesbeth: a team of forensic scientists has calculated what her children will look like in about twenty years. Liesbeth breaks down in tears when she sees her future. This really was fantastic television for the last week of 2016.

TWITTER IS TOUCHED
On Twitter people shared Liesbeth’s emotions with tissues at hand. However, some people had to get used to the hosting of Ruben Nicolai, who took over from Nance Coolen.

Source: LindaNieuws
By: Belinda Janssen

Deaf and almost blind Jeff moves and inspires with song

He was born deaf. And he will become blind as well. Jeff Horsten sings a self-written song about his restrictions on YouTube. The 23 years old man from Waspik, the Netherlands, suffers from Usher Syndrome, a very rare disorder. Still, Jeff surprises the people around him with his laughter, his creativity and his optimism. ‘I want to inspire people. I do not see myself as a person with restrictions. I am just Jeff.’

‘I want to show other people suffering from Usher Syndrome that they are not alone’

The film of his song ‘Welkom in mijn wereldje’ [Welcome to my small world] has been watched thousands of times and dozens of people have shared it on Facebook. The film was put on-line a couple of weeks ago. ‘Tears’, ‘respect’ and ‘goosebumps’ are responses to the touching song. ‘I want to show other people suffering from Usher Syndrome that they are not alone’, says Jeff.

He sings the song together with singer Jorien Habing. The text is about the ‘tunnel’, as the man from Waspik experiences his life. It refers to his deafness and poor eyesight: Jeff looks through two holes of half a centimetre in diameter. ‘People usually can see 180 degrees.’

When Jeff looks at someone, he must move along his head. His eyesight is blurred: now 50 to 60 percent. Jeff will eventually become blind. With the help of his friend, Joep Rijk, Jeff had the song recorded in the Swamp studio in Raamsdonk. The idea came up in rehabilitation centre Het Loo Erf in Apeldoorn, where Jeff has spent nine months by now.

‘It was a kind of game to me. Suddenly all emotions are lost.’

Music
He hated music for years, just because he could not hear it. “One moment I heard Ring of Fire by Johnny Cash. I managed to listen to the rhythm. Later I started to experiment with music. I tasted it and I likes it. I sometimes take a guitar and play a little. However, it remains difficult because I cannot listen well myself.’

Jeff has plenty of texts. He writes a lot. ‘Writing is my way of release. It provides a means to express myself. As a teenager I often picked up the pen. It was a kind of game to me. Suddenly all emotions are lost.’

Source: Algemeen Dagblad

Stichting Ushersyndroom finances restart of ‘minigenes’

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

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

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

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

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

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

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

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

Zebrafishes hope for the future?

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

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

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

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

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

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

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

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

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

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

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

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

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