Frequency 4,5%
18.000 patients
Gene name: PCDH15 (also known as: CDHR15, DFNB23, USH1F)
Gene size: 9237 (bp)
Protein name: Protocadherin-15
Protein size: 1677 (aa)
There are 36 different transcripts known for this gene
TRIALS
There are currently a number of trials that may be relevant to patients with mutations in the USH1F gene:
- Stem cell therapy jCyte
- Stem cell therapy Cedars-Sinai
- Medicine SLO-RP and NAC-ATTACK
- Study vestibulo-cochlear implant (VCI)
NATURAL HISTORY STUDY
The Usher 1F Collaborative in the USA received a large subsidy of $ 450.000 from Facebook top executive Mark Zuckerberg early in the year 2020. A part of the subsidy will be used to start a natural development study, ensuring accurate evaluation of future trials for effectiveness.
MEDICINES SLO-RP
In Australia, a clinical trial phase 1/2 was started with financial support from the Foundation Fighting Blindness.
Nacuity Pharmaceuticals launched this trial under the name SLO-RP. The safety and effectiveness of the medicine NPI-001, an experimental antioxidant, will be tested in the coming two years. The medicine appears to be really promising for slowing down the deterioration of eyesight with people suffering from RP and Usher Syndrome, irrespective of which gene is defective or which mutations have taken place.
MEDICINES TO REDUCE ER-STRESS
Westerfield and colleagues are busy testing various medicines against Parkinson’s disease and Alzheimer’s disease in their zebrafish models for Usher Syndrome. Expectations are that this will slow down the deterioration of the hearing and eyesight of the zebrafish.
GENE REPLACEMENT THERAPY FOR USH 1F
(Source: Usher syndrome Coalition: status and content of study are unknown)
Carvalho and team at University of Western Australia are collaborating with Zubair Ahmed Ph.D, from University of Maryland to develop gene replacement therapy for USH1F. She has developed a dual vector gene replacement therapy, which. Dr. Ahmed. is testing for efficacy on the USH1F mouse model.
DEVELOPMENT OF MINIGENES
David Corey and his team at Harvard Medical School are starting to investigate a reduced Pcdh15b gene (mini-genes). By shrinking the protein of interest of USH 1F, it can be mini-packaged in an AAV vector and then injected into the inner ear and / or retina.
For this study “gene therapy minigenes”, the mice will be used as an animal model to investigate the effect on the mice’s hearing.
A zebrafish will be used as an animal model for research into the consequences of vision.
Jen Philips and Monte Westerfield have developed a zebrafish model Pcdh15b using gene-editing with the Crispr / Cas9 technique.
GENE EDITING
(Source: Usher syndrome Coalition: status and content of study are unknown)
Hewitt and team at the Center Eye Research Australia (CERA) have obtained a grant from the Australian government to support his USH1F research. Utilizing this money, he is working on gene editing to effectively treat the vision loss of Usher 1F.
MOUSE MODEL
(Source: Usher syndrome Coalition: status and content of study are unknown)
Ahmed and his team at the University of Maryland have developed a mouse model of the most prevalent USH1F mutation. They are now using the mouse model to test potential gene therapies and also testing drug therapies.
EXON-SKIPPING THERAPY
With the help of the ‘Moon Rocket Grant’, Stichting Ushersyndroom awarded a grant to the research of Monte Westerfield from Oregon (USA) and Erwin van Wijk (Radboudumc). In this international collaboration they investigate the methodology of “Exon skipping as a future treatment for USH1F patients”.
DEVELOPING A SPLIT DUAL VECTOR SYSTEM
(Source: Usher syndrome Coalition: status and content of study are unknown)
Byrne and team at the University of Pittsburgh are developing. a split gene dual vector system for gene replacement. Her unique approach increases the efficiency of viral vector co-infection, increasing efficacy of large gene expression. Once completed Zubair Ahmed Ph.D. will test her vectors for efficacy in the USH1F mouse model.
STEM CELL THERAPY
jCyte, is a company that has developed retinal progenitor cells (RPCs), a type of stem cell that only retinal cells can become. Clinical studies have shown that these cells can reach and even replace diseased retinal cells. The results of a phase 1 / 2a trial have shown that the treatment is safe and does not cause an immune response.
The Los Angeles-based Cedars-Sinai company has also received approval from the FDA to initiate a phase 1 / 2a clinical trial for patients with RP.
REPAIR DAMAGED RETINAL PHOTORECEPTOR CELLS
(Source: Usher syndrome Coalition: status and content of study are unknown)
Stone and his team at the University of Iowa are working to develop a cure for USH1F along with other types of retinitis pigmentosa. They are working to halt further retinal degeneration from USH1F through gene replacement and to repair damaged retinal photoreceptor cells with new cells made from the patient’s own skin cells with the goal of a clinical trial once safety and efficacy are determined.
ROD-CONE THERAPY
Rod-cone therapy is independent of the gene and focused on treating the rods in the eye while keeping the cones intact. The rods of the retina die first (see light and dark).
INNOVATION AND (MEDICAL) AIDS
Also investigations and studies are conducted in the world that do not specifically offer a solution for people suffering from Usher Syndrome, but that may be of significance for them in the future. Solutions, therapies and medical aids for other disorders can in a later stage be applied to people suffering from Usher Syndrome as well.
IT’S IN THE PROTEINS
The proteins control all processes in our bodies. These proteins are built using codes that have been captured in the DNA. Due to a writing error in the DNA a protein can be produced incorrectly or not at all. Fixing this DNA error changes the production of the protein and so makes the disorder disappear or reduces the symptoms. This is the idea behind the genetic therapies that are now under development throughout the world.
THE CHALLENGES
There are many challenges in research into Usher syndrome. Researchers specifically focus on a methodology, a strategy and / or a specific Usher protein.
