Gene name: CLRN1 (also known as: RP61, USH3, USH3A)
Gene size: 2359 (bp)
Protein name: Clarin-1
Protein size: 232 (aa)
There are 8 different transcripts known for this gene
There are currently a number of trials that may be relevant to patients with mutations in the USH3A-gene:
- Stem cell therapy jCyte
- Stem cell therapy Cedars-Sinai
- Medicine BF844 (start in 2020/2021)
- Medicine SLO-RP and NAC-ATTACK
- Study vestibulo-cochlear implant (VCI)
Dr Yoshikazu Imanishi of Case Western Reserve University in Cleveland (Ohio, USA) is focusing on the development of therapy for Usher Syndrome 3A. One of the most frequent mutations in USH3A is the N48K mutation. Imanishi studies the clarin-1 protein with the N48K mutation in cultivated cells. This study demonstrated that the N48K mutation makes the clarin-1 protein unstable and this leads to the cell quickly destroying the clarin-1 protein again.
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.
A research group of the University of Florida (USA) led by Dr. Dinculescu is working on the development of gene therapy for the retinas of patients suffering from Usher Syndrome type 3A.
Dr. Kumar Alagramam of the University Hospital in Cleveland (Ohio, USA) is doing research into gene therapy with a focus on the development of a treatment for progressive loss of hearing with patients suffering from Usher Syndrome type 3A.
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).
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.
This year in 2021, the North-American foundation Usher III Initiative has taken preliminary steps towards collecting the information necessary to establish the first comprehensive global USH3 patient database. This resource will be critical to the design of future clinical trials and will significantly advance knowledge of the disease and its impact on patients.
There are many challenges in research into Usher syndrome. Researchers specifically focus on a methodology, a strategy and / or a specific Usher protein.
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.