The field of Usher syndrome (USH) research has experienced remarkable advancements over the past few years, outpacing the progress seen in previous decades. As research into potential cures and treatments for USH continues to evolve, it's not uncommon for the various approaches used to be somewhat bewildering, with different researchers pursuing varying strategies. Moreover, some research is gene-specific, while others take a broader approach.
Here, we'll explain some of these different research approaches.
Natural history (NH) studies are used to track the progression of a disease in a patient over time. USH NH studies usually requires many trips by a patient to a designated centre for regular tests such as eye exams, balance tests, hearing tests, and more, depending on the predefined set of data required by the study. These studies, especi
Natural history (NH) studies are used to track the progression of a disease in a patient over time. USH NH studies usually requires many trips by a patient to a designated centre for regular tests such as eye exams, balance tests, hearing tests, and more, depending on the predefined set of data required by the study. These studies, especially for rare diseases, are important as their results may provide better understanding to both patient and clinicians of what a patient may expect from their disease. They may also be valuable for use in clinical trials as researchers would be able compare the results of the NH studies to data from clinical trials.
Gene replacement modifies a specific gene by replacing the faulty gene with a functional copy using AAV. This method is gene-specific and would mean many different gene therapy trials would need to be undertaken to find a treatment for each sub-type of Usher syndrome. There is also the issue that currently this approach may only work for
Gene replacement modifies a specific gene by replacing the faulty gene with a functional copy using AAV. This method is gene-specific and would mean many different gene therapy trials would need to be undertaken to find a treatment for each sub-type of Usher syndrome. There is also the issue that currently this approach may only work for some USH sub-types due to some of the USH genes being too large for a single AAV.
What are AAV? AAV are sdeno-associated viruses! These are harmless viruses that have been adapted into a viral vector to carry a functional copy of an affected gene to the targeted area. To overcome their limited packaging capability, researchers are quickly working on ways to create a dual-AAV vector which may hold bigger genes.
The game-changer to gene therapy is the gene editing CRISPR/Cas9 technology.
This is a new technique that can edit a section of a faulty gene by using a “molecular scissors” to cut and replace it with a functional copy. Similar to gene replacement, it uses AAV to deliver the CRISPR/Cas9 protein ("molecular scissors") and a functional copy of a section of the affected gene to the targeted area.
Stem cell therapy focuses on using cells, rather than genetic materials as used in gene therapy, to treat a range of diseases.
In IRDs therapies, these stem cells are programmed into induced pluripotent stem cells (iPSCs) which are then differentiated into retinal cells for research. Scientists hope this approach may one day replace lost
Stem cell therapy focuses on using cells, rather than genetic materials as used in gene therapy, to treat a range of diseases.
In IRDs therapies, these stem cells are programmed into induced pluripotent stem cells (iPSCs) which are then differentiated into retinal cells for research. Scientists hope this approach may one day replace lost photoreceptors for USH patients and perhaps restore vision.
Antisense oligonucleotide (AON) is a therapy that is designed to target RNA of a faulty gene.
The role of RNA is convert the information stored on a DNA into proteins. Therefore, when the RNA tries to reads a faulty gene it can result in faulty expressions in protein making, possibly leading to severe consequences, such as hearing and sig
Antisense oligonucleotide (AON) is a therapy that is designed to target RNA of a faulty gene.
The role of RNA is convert the information stored on a DNA into proteins. Therefore, when the RNA tries to reads a faulty gene it can result in faulty expressions in protein making, possibly leading to severe consequences, such as hearing and sight loss associated with USH. AON approach is to “silence” the fault in order for the RNA to skip over it and begin creating the protein needed thus stabilising against further loss.
When all of the photoreceptor cells in the retina have degenerated with no vision remaining, gene replacement tends to be no longer a viable option to restore vision. However, despite the death of these cells it is known that the retinal ganglion cells (a layer of cells behind the photoreceptors) remain active in many cases.
Optogenetics
When all of the photoreceptor cells in the retina have degenerated with no vision remaining, gene replacement tends to be no longer a viable option to restore vision. However, despite the death of these cells it is known that the retinal ganglion cells (a layer of cells behind the photoreceptors) remain active in many cases.
Optogenetics involves delivering a gene that expresses a light-sensitive protein to these retinal ganglion cells to work a somewhat similar role of the lost photoreceptors. With the help of special glasses, it's hoped that this method may one day restore some sight to those who are completely blind by an IRD.
Other approaches being investigated by researchers:
ORAL ANTIOXIDANT THERAPY
Nacuity Pharmaceuticals SLO-RP study focuses on the treatment of ocular oxidative stress in the retina which they believe may potentially slow down the degeneration of the photoreceptors cells as experienced by patients with RP.
Did you know that as well as providing support and information, Usher Syndrome Ireland actively supports research efforts aimed at gaining a deeper understanding of this rare condition and working towards a treatment? In 2022, we initiated our inaugural research project in partnership with Stichting Ushersyndroom, and we're committed to advancing more research! Your contribution today can make a significant difference. Please consider donating to support our mission.
Call/Text
+353 (89) 262 4696
(Mon-Fri 10am-4pm)
Registered Address
15 Windsor Terrace,
Dun Laoghaire, Co. Dublin,
A96 RF29
Registered Charity Number: 20206288
CRO Number: 688621
Copyright © 2021 - 2024 Usher Syndrome Ireland - All Rights Reserved.