Also researches and studies are conducted in the world that do not specifically offer a solution for people suffering from Usher Syndrome, but that can be of significance in the future. Solutions, therapies and medical aids for other disorders can in a later stage be applied to people suffering from specific types of Usher Syndrome as well.
‘Balance belt’ for patients with loss of balance
The BalanceBelt has been developed for people with failing organs of balance and is meant for maintaining balance. Our brain combines information coming from various systems in order to reach equilibrium/balance. Apart from information coming from the organs of balance in both ears, this also includes information from the eyes and from the rest of the body (such as the muscles and, more specifically, the muscle spindles).
The BalanceBelt strengthens the information coming from the muscle spindles by giving vibration signals when someone is about to loose his balance. The person wearing the belt then automatically corrects his body posture.
The first results of clinical pilot studies in a hospital environment and at home are highly satisfactory. The BalanceBelt can be a help for people suffering from Usher Syndrome type 1, because the information that the brain receives from the eyes decreases in the course of life, so this information from the eyes can less contribute to maintaining balance. This can make a person dependent on other balance systems.
The BalanceBelt strengthens the information coming from the muscle spindles and can thus improve balance.
The BalanceBelt is an aid that not only – literally – keeps people more in balance, but it also gives them enough confidence to pick up daily life again. The balance belt is an idea of Professor Herman Kingma of the Maastricht UMC+ and was developed in cooperation with engineers of the University of Maastricht, the Netherlands. The licence rights are now transferred to the company Elitac BV in Utrecht, the Netherlands, which is specialised in so-called haptic wearables (technology in which communication with the user is established through movement or vibrations).
The objective is to make this aid available to patients through referral by an ENT specialist. It is still to be determined in consultation with the health insurance companies whether the BalanceBelt will be fully or partially covered.
The vestibular implant
Under normal circumstances the organ of balance records movements of the head. These movements of the head are converted into electrical signals that are passed on to both equilibrium nerves. These signals are processed inthe brain and in this way movements are observed. This leads to, among others, image stabilisation, balance and spacial orientation.
With people suffering from Usher Syndrome type 1 the organ of balance is not functioning, as a result of which these bodily functions can be disrupted.
The purpose of the vestibular implant is to partly recover the functions of the organs of balance. The implant has been composed of an external part which, just like a cochlear implant, can be magnetically connected with the surgically implanted internal part. This surgery is similar to that of a cochlear implant. The external part includes, among other things, gyroscopes, which observe and measure the movements of the head. Subsequently, a microprocessor converts this information into electrical signals. These electrical signals are passed on through the internal part of the implant to the ends of the equilibrium nerve in the organ of balance.
A team of researchers and physicians in Maastricht and Geneva is conducting pilot studies into an artificial organ of balance and/or vestibular implant for patients whose organs of balance have both failed.
‘We implanted the VI with the first people in 2012’, ENT specialist Raymond van de Berg (Maastricht UMC+) tells us. ‘We are still in the testing phase, but the results are promising. We believe that this will be more widely applicable in the future.’
His colleague Joost Stultiens (research physician Maastricht UMC+) is doing a study into the further development of the implant. He tells us: ‘We found out that we could recover certain functions of the organs of balance of the patients who had undergone surgery. We are now further improving the implant and the implanting technique.’
Recently, the researchers in the Maastricht UMC+ were granted a large subsidy for testing the use of a vestibular implant (VI) in daily life with a number of test persons. This is a major step on the way to the objective to make available the VI to all patients with failing organs of balance on both sides in a few years. Apart from this, people are working on the development of a vestibular and cochlear implant in one, the so-called vestibulo-cochlear implant (VCI).
The optogeneticcochlear implant
Researchers of the University Medical Centre Göttingen in Germany are busy developing an optogenetic cochlear implant with 100 channels by making use of micro-LEDs as light source. First, by means of gene therapy the auditory cells are made sensitive to light so they can be activated by light. An optogenetic cochlear implant stimulates the auditory nerve not with electrical stimuli but with light. This technique should offer a much richer and more detailed sound quality than the current electrical stimulation.
The researchers have demonstrated by now that the approach is successful with mice with a 1-channel optogenetic cochlear implant. Researcher from Copenhagen demonstrated early July 2016 that they were able to recover the hearing of deaf rats with a 10-channel version of the optogenetic cochlear implant.
Various types of implants are under development for recovering the eyesight in an artificial way. The various implants are found at another place in the visual system. This visual system runs from the eye to the brain. Studies with test persons are globally conducted in various clinics. The target group for this application generally consists of patients suffering from retinitis pigmentosa in an advanced phase.
- On the retina (epiretinal)
The epiretinal implants work by means of glasses with a camera passing on images to the optic nerve which is connected with the brain. Just like with a cochlear implant, an electrode is first implanted in the retina of the eye. The glasses are connected with the electrode. Examples are SSMP’s Argus II and Pixium Vision’s Iris.
- In or below the retina (subretinal)
In case of subretinal implants a chip is placed in the retina. This chip is powered by means of a box behind the ear. Subretinal implants do not always require special glasses. The chip converts images coming in through the eye into electrical signals. These signals go through the optic nerve to the brain. An example of this is the Retina Implant Alpha AMS/IMS. However, the company Retina Implant is bankrupt, as a result of which this implant is not available for the time being.
Similar implants are being developed by the University of California in San Diego, USA. They make use of a grid of nanowires. However, this is still in the animal model research phase.
- Directly on the brain (cortical)
Various groups around the world are trying to make implants that can be directly connected with the area in the brain that is responsible for seeing (visual cortex). These in fact skip the eye and the optic nerve. The first cortical implants were implanted in completely blind people already in 1967 (Brindley and Lewin) and in 1976 (Dobelle), but these were successful only for a short time. The last few years, research has been done actively into the possibility of implants in the brain. However, at this moment these only include studies in the lab and with test animals. In the Netherlands the NESTOR group is working on this.
Artificial retina (optogenetics)
Another therapeutic approach towards recovering the eyesight is the optogenetic retina. This therapy is intended for patients who have lost all of their photoreceptors.
The idea of optogenetics is not to recover the photoreceptors, but to transform other cells in the eye that have not been affected by the disease and to make them photosensitive. These include other cells (so no photoreceptors) that have been connected with the optical nerve. These cells are injected one-off with gene therapy, making them sensitive to infrared light. Transformed cells are not activated by natural light.
With special glasses camera images are converted into infrared images. This infrared light is sent to the transformed (optogenetic) cells. These cells then send a biological signal to the optical nerve.
A visual implant as described above converts images into pixels, which are sent by means of electronic signals. Optogenetics is a development that is like a retina implant, but as the intervention takes place at cellular level, this will hopefully produce a more refined visual image.
At this moment this study it still in an early innovative phase with animal models.
Additionally, mathematical researchers try to further develop the specific cameras for optogenetic retina for even more precise coding of spacial vision and creating an image with more contrast.
Rod-cone therapy is independent of the gene and focused on treating the rods in the eye while keeping the cones intact. With Usher Syndrome, the rods of the retina die first (see light and dark). Then the cones, which are more important for seeing because they enable us to read and to see colours, degenerate.
The rods are important for night vision, but they can also produce proteins that are essential for survival of the cones. When a rod degenerates, the cones also degenerate after this.
Professor Sahel from Paris demonstrated in various animal models with rods-cones dystrophy such as retinitis pigmentosa that he could protect the cones by means of this therapy. Even the structure of the cones, the morphology, was improved. A clinical trial with a selective group of patients will start in 2020.
Hopefully, this trial will prove that the degeneration of the cones can be prevented. Subsequently, this therapy is to be tested in a much larger group of patients, including patients suffering from Usher Syndrome and retinitis pigmentosa.
Stem cell therapy for treatment of retinitis pigmentosa
Stem cells are unripe cell that can divide but also specialise into specific cells for other tissues. Stem cells can develop into virtually every cell type in the body, which makes them versatile. Progenitor cells of the retina can differentiate into photoreceptors – rods and cones. They cannot develop into non-retinal cells, such as bone, fat or muscle cells.
When used for therapy, these retinal progenitor cells can fulfil two important functions. The first function is that they can produce grow factors with the possible result that the damaged retinal cells can be saved and the disease is slowed down. Another intended application of progenitor cells is inserting differentiated forms of the cells into the retina, replacing the dying retina cells by healthy cells.
As the eye has few immune diseases, the body does not often regard transplanted progenitor cells as foreign intruders and rejection responses are considered to be unlikely. Because of this, patients probably have to make no or little use of additional medication to prevent rejection responses. The first clinical studies, testing applications of progenitor cells in patients with various eye disorders, were focused on studying the safety of this type of treatment. Most of these studies come to the conclusion that this type of treatment is generally tolerated well and safe. As studies into the safety only involve small numbers of patients, no scientifically well-based statement can be made about the effectiveness.
Cell therapy company jCyte has published preliminary results of a phase 1/2a clinical study for its study product, jCell, in retinitis pigmentosa (RP).
According to the company, the study, which covered 12 months, demonstrated that the application of jCell was safe and that a positive effect was seen. jCell has been recognised by the FDA for both orphan drugs and for regenerative medicine advanced therapy (RMAT).
In this treatment retinal progenitor cells are injected into the vitreous humour of the eye under local anaesthesia. It is hoped that diseased photoreceptors can be saved and be reactivated before they die.
The clinical trial phase 1/2 demonstrated that not only the development of retinitis pigmentosa was slowed down, but that some improvement was achieved as well.
The phase 1/2a study included 28 test persons. Observed side-effects are generally minor and only temporary. However, results from this study have not been published in scientific journals yet.
The company launched a larger phase 2b controlled study in order to judge the effectiveness of jCell. With support from the California Institute for Regenerative Medicine (CIRM), 85 patients have been included in the study phase 2b. Participants receive one jCell injection or a placebo. The effectiveness will be judged by testing the visual fields of vision, contrast sensitiveness, quality of life and the ability of participants to navigate through a labyrinth.
Usher Syndrome and DNA diagnostics
From DNA to protein
Development of a therapy for USH type 1
Gene therapy for USH type 1
Development of a therapy for USH type 2
Gene therapy for USH type 2
(Gene) therapy for USH type 3
Research into unravelling and a treatment for Usher Syndrome costs a lot of money. As Usher Syndrome is a rare disease, the governments makes little money available to stimulate research. The mission of the Usher Syndrome Foundation is: ‘A treatment for Usher Syndrome in 2025!’ Help us and donate for scientific research, giving all people suffering from Usher Syndrome a realistic prospect of treatment.
#stopUSH and make our dream come true!
Also read ‘Who knows USHIE?’ and find out how USHIE you can help collect a million euros for scientific research.
This series was established thanks to:
Ivonne Bressers, Cindy Boer en Willem Quite (Ushersyndroom Foundation),
Ronald Pennings, Erwin van Wijk, Erik de Vrieze en Bas Hartel (Radboudumc), Esmee Runhart en Patty Dhooge(Radboudumc),
Joost Stultiens (Maastrichtumc+),
Lisé Nijman (English translations)