Gene name: MYO7A (also known as: DFNA11, DFNB2, NSRD2 or USH1B)
Gene size: 7483 (bp)
Protein name: Myosin 7A
Protein size: 2215 (aa)
There are 14 different transcripts known for this gene
There are currently a number of trials that may be relevant to patients with mutations in the USH1B gene:
- Stem cell therapy jCyte
- Stem cell therapy Cedars-Sinai
- Natural history study USH 1B
- Gene therapy USHTher (start in 2020)
- Medicine SLO-RP
- Study vestibulo-cochlear implant (VCI)
NATURAL HISTORY STUDY
For USH 1B, a natural history study with 10 patients was started in the Rotterdam Eye Hospital in the summer of 2018. This study, funded by Foundazion Telethon, is part of a larger study. In addition to the Rotterdam Eye Hospital, this study also involves institutes in Naples and Madrid. The study is in preparation for the start of the USHTher clinical trial, a gene therapy using double AAV vectors.
GENE THERAPY @USHTHER
Dr. Alberto Auricchio from Naples (Italy) is doing a study into gene therapy for USH 1B. He is studying the possibility to deliver a healthy MYO7A gene by means of a double AAV vector in the retina. Auricchio, with the help of a European grant and Foundazion Telethon, tested the study in larger animal models.
The team now plan on carrying out a clinical trial starting next year. The natural course studies in Naples, Milan and Rotterdam are part of this research.
GENE THERAPY WITH DOUBLE AAV-VECTOR
Also Shannon Boye, Ph.D at the University of Florida, is engaged in the development of gene therapy using a double AAV vector for USH 1B. This research was funded by Fighting Blindness. In the summer of 2020, researchers set up an internal lab ‘Atsena Therapeutics’ (with funding from investors and Fighting Blindness) to further develop the double AAV vector and bring it to the clinic.
(NOTE: It is unknown how this study differs from Dr. Auricchio’s study in Naples @USHTHER).
GENE THERAPY @USHSTAT
In 2018, Sanofi started a clinical trial of gene therapy using a lentivirus and this trial has been stopped by now. Still, a second trial was started, which follows the long-term effects of those people who have participated in the terminated SAR421869 trial phase 1/2. There is a second study that tracks the long-term effects of those who participated in the discontinued SAR421869 trial.
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 IMPROVED RELEASE OF NEUROTRANSMITTERS
Alaa Koleilat studied three already existing and by the FDA approved medicines that can increase the release of neurotransmitters. Although the results with animal models are promising, these medicines cannot be administered to patients right away. As these medicines have been developed for other diseases, their effectiveness and safety in the ear are still unclear.
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.
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.
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).
INNOVATIONS 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.
CREATE A NONHUMAN PRIMATE MODEL
Dr. Neuringer and her colleagues, received a $ 300,000 grant from Fighting Blindness in 2018 to develop a large animal model. Neuringer are using the gene-editing technique CRISPR/Cas9 to develop a large animal model of Usher type 1B, which is caused by mutations in the gene MYO7A. She believes that these animals will exhibit vision loss and will therefore be useful for testing potential Usher 1B therapies.
CHARACTERIZATION OF EXISTING AND NEWLY DEVELOPED MODELS
University California, San Francisco. Jacque Duncan, an experts in genetics and cell biology will create new models using zebrafish, 13-lined ground squirrels and retinal pigment epithelial cells from iPSC to study how the genes and proteins associated with Usher syndrome contribute to photoreceptor structure and survival.
IT’S IN THE PROTEINS
The 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.
There are many challenges in research into Usher syndrome. Researchers specifically focus on a methodology, a strategy and / or a specific Usher protein.