Tag Archive for: Usher syndrome

The Lifelong Vision Project

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CONSORTIUM RECEIVES 22 MILLION EUROS

In an ambitious attempt to combat blindness, a consortium of leading researchers led by Prof. Caroline Klaver from Radboudumc has launched the mission “Lifelong Vision.” With an award of 22 million euros from the NWO Gravity program of the Ministry of Education, Culture and Science (VWS), this project aims to develop revolutionary treatments for blindness.

Blindness ranks among the top 15 most disabling conditions and affects both young and old. The project focuses on Inherited Retinal Disease (IRD), including Retinitis Pigmentosa and Usher Syndrome. In the Lifelong Vision project, scientists in the fields of molecular biology, regenerative medicine, epidemiology, and artificial intelligence will join forces to find patient-centered solutions for blindness.

Knowledge, innovation, and answers to questions.
So, what exactly will the Lifelong Vision project bring? It won’t deliver direct mutation- or gene-specific treatments for individual retinal diseases like Usher Syndrome, but it will provide answers to overarching questions:

Can we revive lost vision and photoreceptors (regeneration)? Can we use AI and 3D bio-printing to print and implant new cells? Can we efficiently and effectively correct hereditary errors? Can we deliver genetic therapies to the retina more efficiently? These are long-term projects with a high risk of disappointing outcomes.

For the development of personalized therapies (for example, for USH2A, 2C, and 1F), subsidies from Stichting Ushersyndroom, Uitzicht, ZonMW, Foundation Fighting Blindness, and other funds are still essential. The Lifelong Vision project will serve as an umbrella under which these specific projects will be linked. Knowledge from Lifelong Vision will be used to make treatments for Usher Syndrome more effective, specific, and safer. The involved researchers in the consortium could never have gained this very specific knowledge and insights without this special subsidy of 22 million.

Gene-editing: precision in gene repair
A crucial part of the Lifelong Vision project is the development of genetic therapies. Researchers will focus on accurately repairing errors in genes, rather than replacing entire genes. This precision approach could be a promising step forward in treating vision problems caused by genetic abnormalities.

Artificial Intelligence: customized treatments
To ensure that the right patients receive the right treatment at the right time, artificial intelligence (AI) will also be developed. These AI systems will help identify suitable candidates for the therapies developed in this project.

Protection of eye cells and cell therapy: inspired by zebrafish
Additionally, researchers are looking into how to protect cells in the eye. Extensive research has already been done on why a cell in the eye with a genetic defect dies. This provides clues on how to keep cells alive, for example, with a special cocktail of proteins that help the cells. Unlike humans, zebrafish have the ability to regenerate dead cells in their retina. This process is also known as regeneration. By carefully studying and better understanding this process in zebrafish, scientists hope to gain new insights that will help to activate the regeneration process in humans (regenerative therapy). Erwin van Wijk, a researcher at Radboudumc, is involved in this research, with zebrafish models for Usher Syndrome being central.

Advanced bio-printing: a new retina
Another innovative development within Lifelong Vision is the use of advanced bio-printing technology to produce a new retina. By layering cells on top of each other, researchers aim to create a retina that is compatible with the human eye and can integrate with the choroid.

“With investments like these, we ensure that we remain at the forefront of the scientific world in the Netherlands. This brings important new insights and innovations that we all benefit from. I am proud that we have such scientific talent in our own country. That is not self-evident. Really something to cherish.”
Robbert Dijkgraaf (Minister of Education, Culture and Science)

The Lifelong Vision Consortium
Eight research institutions are participating in the Lifelong Vision project. The project is led by Caroline Klaver of Radboudumc. Other principal investigators include Rob Collin and Ronald Roepman from Radboudumc, Camiel Boon and Arthur Bergen from Amsterdam UMC, and Clarisa Sánchez from the UvA.

About Gravity
The Gravity program encourages excellent research in the Netherlands. The program is intended for scientific consortia conducting innovative and influential research within their field. The goal is to stimulate research programs to achieve breakthroughs of international significance.

Source:
Radboudumc
Amsterdam UMC
Oogvereniging

Patient and researcher: a dynamic duo once again cycling together

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BUT NOW ON A RACING TANDEM WITH GEARS

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’.

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