HOPE FOR USH1B PATIENTS

CLINICAL TRIAL BY AAVANTGARDE TO COMMENCE

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.

Watch the presentation on AAVantgarde’s programs here.

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.

In preparation for this clinical trial, a natural history study has been conducted in subjects at Naples, Madrid, and Rotterdam. This study is essential for establishing inclusion criteria and measuring the effectiveness of the treatment.

 

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jCyte stamceltherapie

jCyte Initiates Phase 3 Clinical Trial for RP Cell Therapy

LEES ARTIKEL IN NEDERLANDS

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.

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Ontwikkeling van een ‘netvlies-op-een-chip’ platform

Foundation supports innovative research into retinal diseases

LEES ARTIKEL IN NEDERLANDS

Development of a ‘retina-on-a-chip’ platform 

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.  

Ontwikkeling van een ‘netvlies-op-een-chip’ platform

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.