On September 16, 2024, AAVantgarde Bio, a biotechnology company from Italy, announced that the first patient has been treated in a clinical study investigating the safety and efficacy of a new gene therapy for patients with retinitis pigmentosa as a result of Usher Syndrome type 1B (USH1B).
This clinical study, named LUCE-1, has been set up to examine how safe and effective the new gene therapy AAVB-081 is in individuals with Usher syndrome type 1B. In this condition, patients lose their hearing and sight due to a hereditary mutation in the MYO7A gene. The study is in phase 1/2, meaning it is still in an early stage and primarily focused on testing safety.
How does the gene therapy work? The new treatment, AAVB-081, utilizes a specialized technique designed to deliver larger genes like MYO7A into the eye. This is done by packaging two halves of the gene into viral carriers, known as AAV vectors, which together complete the MYO7A gene inside the cell. The idea is that this therapy restores the production of the Myo7A protein, which may help stabilize the patient’s vision.
Previously successful results achieved The technology behind this gene therapy was developed by Professor Alberto Auricchio at the TIGEM institute in Naples. As the first-in-human study with this therapy has only just commenced, no data on the results are as yet available. However, scientists have previously studied the therapy in small and large animal models and demonstrated up to 40% improvement in the gene function. As animal eyes have many differences compared to human eyes, comment on the success of the therapy in humans will only be available after the clinical trials. .
First patient The first patient in the LUCE-1 study has been treated at the University Hospital of Campania in Naples, under the guidance of Professor Francesca Simonelli, an expert in ophthalmology and gene therapy. In the coming period, more patients will be treated, and the results will be evaluated.
This study offers hope for individuals with Usher syndrome type 1B, a group of patients for whom there are currently no treatments available to preserve their vision. The success of this therapy would be a significant step forward in the fight against this progressive disease.
More information
AAVantgarde Bio continues to work closely with researchers to further develop this promising therapy and hopes to assist more patients soon. Stichting Ushersyndroom is regularly updated by AAVantgarde, and we share this valuable information with our supporters through our website, newsletter, and social media. The full results of the study will be announced once the study is completed and the data analysed, although this will take several years.
https://www.ushersyndroom.nl/wp-content/uploads/2024/09/Aavantgarde-voorblad-1.png425800Ivonne Bressershttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgIvonne Bressers2024-09-27 15:35:232024-10-01 21:32:14First patient treated in clinical study for gene therapy for Usher syndrome type 1B
Recent research by Mirthe Fehrmann and colleagues at Radboudumc has provided significant new insights into the long-term outcomes of cochlear implantation (CI) in people with Usher syndrome. The study focused on the effectiveness of cochlear implants in different subtypes of the syndrome (USH1, USH2, and USH3), with a special emphasis on long-term outcomes. The findings have been published in the renowned journal Ear & Hearing.
Usher syndrome is a hereditary disorder characterized by a combination of hearing loss or deafness and progressive vision loss due to retinitis pigmentosa (RP). As a result, people with Usher syndrome rely heavily on their hearing for communication and orientation. Cochlear implants (CI) offer a solution for many, but until now, there has been a lack of extensive studies examining the long-term effectiveness of CI in the various subtypes of Usher syndrome.
Study design The study examined 36 patients with Usher syndrome who received cochlear implants at Radboudumc (53 ears). The patients were divided into four groups: early-implanted USH1, late-implanted USH1, USH2, and USH3. Speech recognition with CI was measured at various time points after implantation: at 1 year, 2 years, and 5 years or more.
The study aimed to evaluate the performance of cochlear implants in people with different subtypes of Usher syndrome in both the short and long term. The focus was on improvements in speech recognition and overall satisfaction with the implantation.
Key findings
USH1 (early implantation, younger than 7 years): Early-implanted patients (median implantation age = 13 months) achieved excellent results, with 100% speech recognition after an average of 12 years. Early, simultaneous bilateral implantation led to much better speech recognition than sequential implantation.
USH1 (late implantation, older than 7 years): In late-implanted patients, CI was primarily used for sound detection, with an average speech recognition of only 12%. However, these patients were satisfied with their ability to perceive environmental sounds and used the implant more as a signaling device.
USH2: Patients with USH2 who received a CI generally achieved good results, with an average speech recognition of 85% after 8 years of follow-up. Early implantation and better speech perception with hearing aids before implantation led to better results. Delaying the decision to receive a CI if eligible is therefore not advisable.
USH3: Results in USH3 patients were more variable, with an average speech recognition of 71%. The small number of patients in this group and the fact that some had been severely hearing impaired for a long time before receiving a CI explain the variation.
* For more information on the different subtypes of Usher syndrome, read here.
This study demonstrates that cochlear implants are effective in improving hearing in people with Usher syndrome, both in the short and long term. For patients with USH1, early bilateral implantation is strongly recommended for the best results. Late implantation, while providing a signaling function, is not sufficient for effective oral communication.
In USH2 and USH3, early implantation is crucial to slow the progression of hearing loss, especially given the severe visual impairments. For USH2 patients with sufficient speech recognition before implantation, the results are particularly favorable. In USH3, the variability of symptoms creates more uncertainty regarding outcomes, requiring careful counseling. However, it is expected that when implanted early enough, USH3 patients can achieve results comparable to those in USH2.
Practical implications
Early implantation is crucial to achieve optimal results.
Simultaneous bilateral implantation, ideally between 6 and 12 months of age, is recommended for USH1 patients to maximize speech recognition and hearing performance.
USH2 and USH3, good results are achievable, especially when patients have received sufficient auditory stimulation and used hearing aids before implantation. When speech recognition with hearing aids falls below 70% (at 65 dB speech), CI can already be considered.
Counseling and education should emphasize the importance of early detection and timely implantation, as well as encouraging the use of hearing aids to keep auditory pathways active.
These findings support a proactive approach to the treatment of Usher syndrome:
Screening and early diagnosis are essential to intervene in a timely manner and improve the quality of life for patients.
Multidisciplinary collaboration between audiologists, ophthalmologists, geneticists, and rehabilitation specialists can contribute to an integrated care approach.
Individual treatment plans should be developed, considering the specific subtype, symptom progression, and the patient’s personal needs.
With timely and appropriate treatment, patients can experience significant improvements in their hearing, leading to better communication and an enhanced quality of life despite the challenges of the syndrome.
Erwin van Wijk (Radboudumc) has recently received a substantial grant from the Foundation Fighting Blindness USA to create a large animal model in collaboration with the research groups of Klymiuk (LMU Munich, Germany) and Ellederova & Motlik (PIGMOD Center, Libechov, Czech Republic): a USH2c pig model. This development marks a significant step towards effective treatments for patients with USH2c.
Accelerating therapy development The grant for developing a USH2c pig model is crucial for accelerating therapy development for USH2c. This model enables the final critical studies, such as tests on the effectiveness, dosage, and toxicity of various therapies for USH2c. Currently, such studies cannot be performed with the available cell and zebrafish models for USH2c. The pig model allows researchers to take these essential last steps before therapies enter the human trial phase.
The pig eye: A valuable model Although more alternative cell models are becoming available, it is unfortunately still not possible to develop new therapies without the use of animal models. Efforts are being made to reduce the use of animal models as much as possible, in accordance with the 3R principle: Replacement, Reduction, and Refinement. All new therapies are first extensively tested in human cell models and the previously developed USH2c zebrafish model. While these are excellent models for fundamental and translational research, they are not suitable for determining the long-term effects and safety of new treatments.
The pig eye closely resembles the human eye, both in size and morphology, and has already proven its value as a model for Usher syndrome type 1c.
A humanized USH2c model The proposed model will be a ‘humanized’ USH2c pig model, where parts of the pig USH2C gene are replaced with the human USH2C gene, including the mutations that cause Usher syndrome. This humanized model provides the opportunity to test a wide range of current and future therapeutic strategies.
Goal and impact of the project The main goal of this project is to generate a multifunctional humanized pig model for USH2c, in collaboration with the research groups of Nikolai Klymiuk (LMU Munich, Germany) and Jan Motlik & Zdenka Ellederova (PIGMOD Center, Libechov, Czech Republic), who specialize in generating and phenotyping pig models.
Erwin van Wijk’s research group in Nijmegen will design the pig model and produce the necessary components for its creation. In Munich, the pig will actually be created, and in the Czech Republic, a group of pigs will be bred, followed by phenotyping (analysis of vision and hearing function). Finally, various genetic analyses will be conducted in Nijmegen (at the DNA, RNA and protein levels). The project has a duration of three years.
The model is designed to determine the effectiveness of all forms of genetic therapy (RNA therapy, (mini)gene therapy, translational read-through therapy, CRISPR therapy, etc.). This model enables the translation of effective and safe therapeutic treatments from pig to human.
https://www.ushersyndroom.nl/wp-content/uploads/2020/03/science-2C.jpg13921385Ivonne Bressershttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgIvonne Bressers2024-07-05 14:45:102024-09-25 11:59:15An important next step in USH2c research
NEW RESEARCH THANKS TO
THE ‘USHER ACTIE RIJNSBURG’ FRIENDS GROUP
The ‘Usher Action Rijnsbrug’ group of friends present the check to Dr. Suzanne Yzer. From left to right; Marjolein, Liesbeth, Suzanne, Annemarie
Usher syndrome, characterized by sensorineural hearing loss and progressive Retinitis Pigmentosa (RP), presents a significant challenge for the medical community. With the most involved gene, USH2A, treatments for Retinitis Pigmentosa are becoming increasingly promising. The use of correctly chosen endpoints will prevent unnecessary failures of potentially effective treatment studies and accelerate the development of treatments.
Thanks to the years of unwavering enthusiasm and dedication of the ‘Usher Actie Rijnsburg’ group, Stichting Ushersyndroom can financially support an important study into the right biomarkers and endpoints.
Correlation between structure and function In this study, led by Dr. Suzanne Yzer, ophthalmologist at Radboud University Medical Center in the Netherlands, researchers aim to examine the retinas of patients with Usher syndrome by combining existing ophthalmic examinations with newly developed imaging techniques. The combined information will provide a more detailed correlation between the structure and function of the retina, yielding essential data for a comprehensive analysis. This will enable the identification of the best biomarkers and endpoints for clinical trials for Usher syndrome patients. Biomarkers and endpoints that will aid in treatment trials (clinical trials), ensuring that outcomes and information are indisputable and provide evidence of treatment effectiveness.
“Correctly chosen endpoints help prevent the unnecessary failure of a potentially groundbreaking treatment study.” Dr. Suzanne Yzer, Ophthalmologist at Radboud University Medical Center
Delay A poorly designed study or wrongly chosen biomarker or endpoints can lead to years of delay before the therapy becomes available to patients. This is not only a significant disadvantage for the specific treatment but will also deter investors from supporting new studies.
Incorrect endpoints The failure of a treatment study does not necessarily mean that the investigated therapeutic treatment is ineffective. Studies may fail because of inaccurately chosen inclusion criteria or endpoints. In August 2022, ProQR’s clinical trial was halted for this reason. The endpoints for another clinical trial (for LCA) were not accurately defined, resulting in them not being met. Investors withdrew, leading to insufficient funding to continue the clinical trial for USH2A exon 13.
The clinical trial has since been restarted; Laboratoires Théa (Théa) has taken over the study.
Existing and new imaging tools With the first clinical trials on the horizon, it is crucial to select the right biomarkers and endpoints. Radboudumc has conducted a large natural history study in a large group of patients with mutations in USH2 genes, the CRUSH study, and the RUSH2a study. Results are expected in the fall of 2024. Since the start of these studies, progress has been made with existing and newly developed imaging tools, such as “Adaptive Optics” and the “High Magnification Module” lens.
Increasing opportunities The current study focuses on identifying the most reliable biomarkers and endpoints for future therapeutic studies in Usher syndrome type 2. By identifying better endpoints, the chances of demonstrating treatment effectiveness will be increased, helping to advance the development of treatments. This will also make it more attractive to accelerate the implementation of new clinical studies, such as gene replacement therapy for Usher syndrome, including minigenes for USH2A and USH2C, and exon excision therapy.
This will ultimately benefit all patients with Usher syndrome. The goal is to achieve successful treatment and administer the drug or therapeutic treatment in the earlier stages of the disease, thus preventing severe loss of photoreceptors. The findings will be published in scientific journals and will contribute to the advancement of gene-specific therapies for retinal diseases.
Thanks to the Usher Action Rijnsburg and the co-financing from the Vaillantfonds and the Aanmoedigingsfonds van de Koninklijke Facultatieve the Stichtig Ushersyndroom can financially support this research.This project is budgeted at € 226.000,- and will last for three years.
Friends group of Liesbeth ‘Usher Actie Rijnsburg’ is a friends group that takes action for their friend Liesbeth and other people with Usher syndrome. They organize various activities and an annual event to raise as much money as possible.
https://www.ushersyndroom.nl/wp-content/uploads/2024/06/radboud-Liesbeth-8-scaled.jpg17072560Ivonne Bressershttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgIvonne Bressers2024-06-11 10:35:252024-09-25 11:59:43What are the best biomarkers and endpoints for future trials?
In a remarkable collaboration between patients with Usher syndrome and researchers from Radboudumc, a crucial next step is made possible in the research towards a treatment for Usher syndrome type 2C (USH2C).
In 2020, researchers and patients embarked on a joint journey in the research on USH2C. The research, funded by Stichting Ushersyndroom (Dutch Usher Syndrome Foundation) with co-financing from L.S.B.S. and CUREUsher, has faced some setbacks, including delays due to the COVID-19 pandemic. Although the research has experienced some delays, the initial results appear to be very promising. Researchers and patients are striving to accelerate this crucial and innovative research. Patients worldwide are uniting to raise funds for the Usher Syndrome Foundation so that a follow-up to this study can be made possible.
Bike ride
In their sporty attire, researcher Merel Stemerdink, cheerfully acting as a co-pilot along with patient (and treasurer of Stichting Ushersyndroom Rick Brouwer as the stoker, cycled to the Railway Museum during the Usher Awareness Day last summer. They cycled over 75 kilometers from Arnhem to Utrecht. Smoothly, focused, and at a fast pace! Merel regularly races in her free time, and Rick is a trained triathlete.
In rare diseases such as Usher syndrome, the contact between doctors, researchers, and patients is crucial. Patients, parents, and loved ones drive scientific research towards a treatment by collecting donations and closely consulting with doctors and researchers. By working together, a treatment for progressive deaf-blindness comes into view more quickly.
Accelerating as a duo on the tandem
Patients with Usher syndrome and researchers from Radboudumc are once again putting the tandem into motion for scientific research towards a treatment for Usher syndrome type 2C. Currently, various treatment strategies, including the USH2C minigenes, are being tested in a USH2C zebrafish model developed specifically for the research. The initial results, which are expected to be announced by the end of 2024, are very promising. Therefore, efforts are being made to raise funds to continue this research beyond 2025.
Promising research USH2C is caused by mutations in the ADGRV1 gene, and these errors in the gene lead to a progressive form of deaf-blindness. One of the promising treatment strategies for inherited blindness is ‘gene augmentation,’ where a healthy copy of the involved gene is delivered to the eye using a viral vector. What makes the development of this therapy challenging is that the ADGRV1 gene is incredibly large: so large that it cannot be packaged into the viral vector. Therefore, artificially shortened versions of the ADGRV1 gene have been created – the ADGRV1 (USH2C) minigenes. These minigenes fit into a viral vector, and currently, it is being investigated using the USH2C zebrafish model whether these mini-genes are actually able to take over the function of the defective ADGRV1 gene.
Another treatment strategy, called ‘exon skipping,’ allows specific exons (the specific regions of the ADGRV1 gene where mutations are located) to be skipped. In theory, this can restore the normal function of the gene. Although this is currently targeted at a smaller group of patients, the initial results in zebrafish provide hope for a more personalized approach to treatment.
Watch here the presentation ‘USH2C Research’ by Merel Stemerdink. With subtitles in Dutch and English.
Researchers and patients A group of Americans contacted Rick Brouwer via the private Facebook group Usher 2C and called the researchers at Radboudumc. Soon, a symbiosis developed between the patients from the USA and the researchers at Radboudumc. Strong involvement between researchers and patients increases motivation and inspiration to further advance and accelerate current research.
Follow-up Study Although the analyses and outcomes have yet to be published, the initial results are very promising. A follow-up study to also test the strategies on human organoids is being designed and will be submitted for advice to the Scientific Advisory Board of Stichting Ushersydroom later this year.
Cindy Boer (member of the Scientific Advisory Board and PostDoc Osteoarthritis, genetics, microbiomics & omics at ErasmusUMC and diagnosed with Usher syndrome herself): “In an earlier advice, we proposed an addition to the research. We want a translation to be made to humans using human skin cells. This allows you to investigate whether the minigenes behave well in human cells and whether the proteins fold correctly. This can sometimes be different from animal models and therefore provides a good indication of whether gene therapy will work in humans.”
Future Plans The research team is also looking towards the future with a postdoc project proposal scheduled for 2025. While the treatment strategies are currently being evaluated in the zebrafish model, the future project will translate these findings to humans. The project will focus on evaluating the treatment strategies in human cells and retinal organoids. The success of these approaches could lead to expansion to other forms of retinal degeneration, and possibly further refinement of ongoing research into new treatments for Retinitis Pigmentosa caused by mutations in the USH2A and USH2C genes.
Jack from the USA is also cycling along!
Taking action together to accelerate research This time, a racing tandem with both a patient and a researcher on board. Patients from Sweden are now also involved, and a global crowdfunding campaign has been launched. With great confidence in the process propelling them forward and bringing a treatment for Usher syndrome closer than ever before. The funds collected are managed by Stichting Ushersyndroom and are earmarked for further USH2C research. The involvement of patients, both locally and globally, is propelling research into USH2C to new heights. These global efforts to raise donations are conducted through the FundMe platform: ‘Fund a Cure for Usher Syndrome 2C’.
https://www.ushersyndroom.nl/wp-content/uploads/2024/03/Schermafbeelding-2024-03-14-om-12.56.14.png9661416YellowDeveloperhttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgYellowDeveloper2024-03-14 13:50:172024-09-25 12:00:08Patient and researcher: a dynamic duo once again cycling together
AAVantgarde, an international biotechnology company based in Italy and co-founded by Professor Alberto Auricchio, is dedicated to overcoming the limitations of adeno-associated virus (AAV) vectors in gene therapy. AAVantgarde has developed its own AAV-based large gene delivery platform for retinitis pigmentosa associated with Usher syndrome type 1b (USH1B), utilizing DNA recombination known as dual hybrid AAV.
By the end of March/beginning of April, the first participant will undergo treatment with the dual hybrid AAV designed by AAVantgarde, marking an exciting period ahead.
Usher Syndrome Type 1B (USH1B) is a genetic disorder characterized by congenital deafness, impairment of the vestibular system, and retinitis pigmentosa (RP). It affects approximately 1 in 50.000 people. The condition is caused by mutations in the MYO7A gene, responsible for producing a protein called MYO7A, which plays a crucial role in various cellular processes, including melanosome localization in the retinal pigment epithelium (RPE) and rhodopsin transport in photoreceptor cells.
Motor Protein
MYO7A is an actin-based motor protein responsible for transporting various substances within the cell. These proteins move along thin fibers called microtubules in a manner resembling walking, with two “feet” that alternately bind to the fiber.
Here you can see a short animation of ‘a walking motor protein’:
Motor proteins consist of a head and a tail portion. The head houses the actual motor and consumes energy. The ‘tail side’ contains docking sites where various molecules can be attached. Because MYO7A is a motor protein, the challenge lies in delivering the entire protein healthily to the eye.
Dual Hybrid AAV
Traditional adeno-associated virus (AAV) gene therapy approaches have limitations due to the size of the genes they can deliver. A newer strategy, known as double hybrid AAV gene therapy, aims to address this challenge. In this approach, splice donor and acceptor signals are separately inserted into two AAV vectors, with recombination designed by AAVantgarde. Recombination involves rearranging genetic material to form a single AAV genome that leads to the production of a full-length functional protein.
Phase 1 and 2 of the Clinical Trial
The first participant is expected to be treated within Q2 2024, with a total of 15 participants to be treated in the study. Safety and effectiveness will be tested at various dosages, with the first results expected to be available by 2025.
Biotechnology company jCyte is gearing up to launch a phase 3 clinical trial in the United States for its jCell therapy, following a successful phase 2B trial and with approval from the U.S. Food & Drug Administration (FDA). The company plans to begin enrolling new participants for the next phase of the trial in the second half of 2024.
Cell Therapy
jCells are similar to stem cells that have not yet fully matured into adult photoreceptors. These cells are injected into the vitreous body, the fluid inside the eye, in the middle of the eye. Through an intravitreal injection, it’s possible to achieve an effective dosage for the eye with a low dose, while the medication only minimally enters the rest of the body. jCells are designed to release proteins known as neurotrophic factors to preserve photoreceptors, regardless of the mutated gene causing vision loss. Neurotrophic factors are proteins that can stimulate the regeneration of damaged nerve pathways in experimental models.
New Experimental Treatments
In recent years, an increasing number of genes have been discovered in which hereditary mutations lead to vision impairment. This knowledge has led to new experimental treatments such as RNA therapy, gene therapy, stem cell therapy, and implanted chips connected to the brain. Stem cell therapy is particularly suitable in later stages of the eye disease, when many retinal cells have already died and gene therapy no longer provides relief.
Positive Phase 2B Results
In a phase 2B clinical trial with 85 patients for jCells, 39 percent of patients received the high dose of the treatment and showed an improvement in visual acuity of 10 letters (two lines on an eye chart) or more. In the lower dosage cohort, 16 percent showed an improvement of 10 or more letters. Significant improvements were also observed in treated eyes in contrast sensitivity, visual fields, and mobility-related visual function (as captured in the VFQ-48 questionnaire). These questionnaires provide an important indication alongside visual functions of whether there is also improvement in daily life mobility.
jCyte is a biotechnology company dedicated to preserving and restoring vision in patients with retinitis pigmentosa (RP) and other degenerative retinal conditions. For more information, visit www.jcyte.com.
More information available at our Knowledge Portal:
An important new study has been launched to offer hope to people suffering from hereditary eye diseases such as retinitis pigmentosa, Usher syndrome, macular degeneration, and Stargardt disease. Led by Dr. Jan Wijnholds of the Leiden University Medical Center (LUMC), researchers are working on a special chip on which they can mimic a piece of human retina. The project is named the “Human retina-on-a-chip platform” and aims to develop an advanced platform for studying the retina and testing candidate drugs.
What is a ‘retina-on-a-chip’? The current research involves ‘retinas-on-a-chip’, miniature culture dishes in which human retinal tissue is grown. This allows scientists to study the retina in the laboratory and test potential treatments. However, these chips have limitations, including a lack of stability of the cultured retinas.
Picture made by Charlotte Andriessen.
Why is this research important? In hereditary retinal diseases, cells in the retina die, eventually leading to blindness. Although there are promising treatments and gene therapies, there is a need for an improved platform to test them. Dr. Jan Wijnholds and his team are focusing on optimizing the existing ‘retina-on-a-chip’ concept.
How will Dr. Jan Wijnholds approach this? Dr. Wijnholds will make a crucial improvement by adding retinal pigment epithelium to the ‘retinas-on-a-chip’. This pigment layer, similar to what is naturally present in the human eye, enhances the stability of the cultured retinas. However, adding functional pigment layer is a technological challenge due to the microscale at which it occurs.
What are the potential benefits? The improved ‘retina-on-a-chip’ platform will enable researchers to more accurately mimic the human retina in the laboratory. This opens the door to a better understanding of healthy and diseased retinal cells, as well as testing new treatments. Dr. Wijnholds will also look for biomarkers, measurable indicators that indicate whether retinal cell death is occurring and how severe it is. These biomarkers can help doctors predict disease progression and measure the effectiveness of treatments.
What does this mean for the future? Although this is fundamental research, it could lead to faster development of treatments for people with retinal diseases. The Usher Syndrome Foundation supports this two-year project with a financial contribution of €100,000, expressing its confidence in the value of this groundbreaking research. The ultimate goal is to offer hope to patients with hereditary retinal disorders by enabling more effective treatments.
https://www.ushersyndroom.nl/wp-content/uploads/2024/02/chip-2.jpeg12001600YellowDeveloperhttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgYellowDeveloper2024-02-16 13:03:462024-09-25 12:00:47Foundation supports innovative research into retinal diseases
In mid-August, we reported that ProQR Therapeutics, which had previously been forced to halt its two promising clinical trials, had found a new partner in Laboratoires Théa (Théa) to continue development. Unfortunately, this collaboration has been terminated prematurely.
One of the conditions for finalizing the agreement was that several key ophthalmic employees of ProQR would enter into employment with Théa. Regrettably, some employees have decided not to proceed with this, making it impossible to meet this closing condition. As a result, Théa has terminated the agreement.
The immediate consequence is that the clinical trial testing RNA therapy for individuals with Usher syndrome 2A will not be resumed at this time.
The new partner Laboratoires Théa (Théa)has signed an agreement with ProQR to continue the further development of the IRD Sepofurses and Ulteverses programs. Théa is European pharmaceutical company specialized in the research, development, and commercialization of eye care products. This family-owned is based in Clermont-Ferrand, France.
Within Théa, a fully dedicated team specializing in inherited retinal disorders and a new organization are currently being set up to manage these projects. More information on the next steps for these programs will be available in the coming weeks from Théa.
About Ultevursen
Ultevursen (formerly QR-421a) is a first-in-class investigational RNA therapy designed to address the underlying cause of vision loss in Usher syndrome type 2a and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. QR-421a is designed to restore functional usherin protein by using an exon skipping approach with the aim to stop or reverse vision loss in patients. Ultevursen is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the US and the European Union and received fast-track and rare pediatric disease designations from the FDA.
The transaction is expected to close in the third quarter of 2023.
For further information or enquiries about the announcement today, please email: patientinfo@proqr.com.
https://www.ushersyndroom.nl/wp-content/uploads/2023/04/DSC_1783.jpg11812341Ivonne Bressershttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgIvonne Bressers2023-09-29 08:19:232023-09-29 10:27:00Resumption of the clinical trial for RNA therapy for USH2a has been terminated
New research on the cause of blindness due to Usher syndrome
A research team led by Dr. Ronald Roepman (www.roepmanlab.com) is conducting research at Radboudumc, Netherlands, to investigate the underlying cause of vision loss in Usher syndrome. In this study, titled “Harnessing Autophagy to Combat Macular Degeneration,” they aim to gain more clarity on the death of cone cells in the retina. In a healthy eye, waste products in the retina are “cleaned up,” but in retinal diseases like Usher syndrome, this process is insufficient. The cones ultimately die because waste accumulates in harmful quantities within these cells. Thanks to the efforts of the participants in ‘Nederland wandelt voor Usher’ (Event Walks for Usher), Stichting Ushersyndroom (the Dutch Usher Syndrome Foundation) can finance a significant portion of this important research.
Crucial discovery
Hereditary blindness is a profound condition that seriously affects the lives of many patients. Researchers have been searching for effective treatments for some time, but the question of why waste products in the retina are not cleared in hereditary retinal diseases has remained unknown until now. Dr. Ronald Roepman, who collaborates in this promising project with Dr. Erik de Vrieze and Dr. Erwin van Wyk, recently made a crucial discovery that may provide an answer to this question. This could be a significant step toward a solution. Dr. Ronald Roepman says, “If you understand why the cones don’t clean up the waste, then you might be able to help them clean it up, perhaps with medication.”
Autophagy
The research focuses on understanding the mechanism of ‘autophagy’ in cone cells. Autophagy is a biological process in which certain components of a cell, such as damaged proteins or foreign particles, are broken down. Recent research data suggest that dysregulation of this process is a significant cause of cone cell death, leading to progressive vision loss in hereditary retinal disorders.
Death due to self-waste
An Usher gene contains instructions for producing a protein that keeps the light-sensitive cells in the retina – the rods and cones – healthy. Errors in this gene can lead to the protein’s malfunction and disrupt the processes. Cones produce substantial amounts of waste products, which are normally cleared through the autophagy process. If the Usher proteins are absent or not functioning properly, the cones cannot dispose of their waste products and essentially drown in their own ‘mess.’ The researchers aim to determine how the genetic defect is responsible for the malfunctioning autophagy.
Zebrafish and retinal organoids
The research team uses zebrafish as a model organism in the laboratory due to the striking similarities between their eyes and those of humans. They will compare healthy cone cells with cone cells displaying disrupted autophagy using zebrafish. Additionally, the research team will use retinal organoids, small retinas grown in the laboratory using cells from both Usher syndrome patients and people with healthy eyes. These organoids provide a valuable platform to study the autophagy mechanism in healthy and diseased cells.
Hope for finding a safe and effective treatment
Once the autophagy mechanism is understood, the research team will search for substances that can stimulate the autophagy process, thereby reducing or preventing cone cell death. With the help of a database containing thousands of substances known to stimulate or inhibit proteins, they hope to find a safe and effective treatment.
Also, for other hereditary retinal diseases
This promising research will not only contribute to detailed knowledge about autophagy and cone cell death but also offer possibilities for further treatment development. If the results of this research prove successful, this project could slow down vision deterioration and have a significant impact on the quality of life for Usher syndrome patients. Dr. Roepman says, “It could offer a solution not only for Usher syndrome but also for patients with Retinitis Pigmentosa (RP), Macular Degeneration (MD), and all other forms of hereditary retinal diseases.”
The current project has a duration of three years. Stichting Ushersyndroom plays a significant role in the research by financing a large portion of the required budget. We are not the sole financiers of this research. Thanks to the L.S.B.S. (National Foundation for the Blind and Visually Impaired) and the donors of the Oogfonds (Dutch Eye Foundation), they are co-funders for this project, providing a valuable financial contribution to make this promising research possible.
You can support us through a donation. With your contribution, the Stichting Ushersyndroom can finance scientific research. Research aimed at finding a treatment for Usher syndrome, so that becoming deaf and blind can be halted!
Every donation is valuable and brings us closer to solutions for Usher syndrome.
https://www.ushersyndroom.nl/wp-content/uploads/2023/09/Usher-UAD-23-10-1-scaled.jpg20482560Ivonne Bressershttps://www.ushersyndroom.nl/wp-content/uploads/2023/08/Website-logo.svgIvonne Bressers2023-09-17 11:38:152024-09-25 12:01:13Who cleans up ‘the mess’ from the cones?
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A research team led by Dr. Ronald Roepman (