Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Proposed therapy, developed in a Pcdh15-deficient mouse, for progressive loss of vision in human Usher syndrome
We previously published about this research in a story titled “Researchers Identify Underlying Mechanism and Possible Treatment of Usher Syndrome” which can be found here. The study was originally published in the journal eLife. You can view the full text of the study here.
This research team was affiliated with University of Maryland School of Medicine.
Type 1F Usher syndrome causes loss of balance, deafness, and progressive retinal deterioration. In a recent study using data from a mouse model and human patients, scientists set out to understand the mechanism behind the retinal degeneration that is observed in the disease. Researchers were able to identify the mechanism and also tested a potential treatment approach based off of their findings.
This study looked at 13 patients living with Usher syndrome type 1F. By age 50, half of these patients were considered legally blind as a result of retinal degeneration. The mouse model was created using the mutation found in these patients, which affected the gene PCDH15. The gene codes for protocadherin-15, which, by comparing healthy mice and the mutated mice, the team found is involved with the movement of light dark cycle proteins. These move between different areas of the eye’s photoreceptors. Protocadherin-15 also recycles retinoids, molecules that are critical for eye tissue function.
The team found that the mutated mice had less retinoids in certain eye cells. The Usher syndrome mice were then given injections of retinoids, which increased levels of electrical activity in mice of all ages. This indicated that the vision of the mutated mice had been improved. The scientists concluded that a similar treatment could provide temporary vision improvement in human patients.
About Usher Syndrome
Usher syndrome is the leading cause of deafblindness (the state of being both blind and deaf); however, the disorder is still generally rare. The syndrome is currently incurable and there are three different types. There are a total of 11 different genes that, if mutated, can cause the disorder. Usher syndrome type 1F is more common in Ashkenazi Jews and has been linked to mutations affecting the PCDH15 gene. Type 1 also affects coordination and balance. Vision loss is linked to retinitis pigmentosa, in which the retinal cells degenerate over time, and hearing loss is due to defects of the inner ear. There is no known treatment that can stop the progression of symptoms; gene therapy may be the most effective avenue for research. The rate of disease progression can vary drastically from person to person. To learn more about Usher syndrome, click here.
Why Does it Matter?
This study is of value for two principal reasons. First of all, it has given researchers greater insight into the mechanism behind retinal degeneration in Usher syndrome type 1F. Second, the researchers found that retinoid replacement can help temporarily relieve symptoms. This gives the team a good starting point to get started on the development of a treatment that could potentially be a real breakthrough for treating the vision loss that is associated with the syndrome:
“Aside from retinoid replacement, we can also think about developing more permanent therapies to treat or prevent blindness in people with Usher syndrome type 1F that may correct or replace the other functions of protocadherin-15, as well.” – Zubair M. Ahmed, Professor of Otorhinolaryngology—Head & Neck surgery and Ophthalmology, University of Maryland
The treatment used in the study could be developed into a viable treatment that could help treat vision problems, and similar treatments have already been cleared by the US Food and Drug Administration (FDA). Others are being evaluated in phase II clinical trials.
“…These drugs will not permanently cure loss of vision, as the drug does not repair damage or prevent degeneration of the eyes. However, it should improve the function of the tissue that these patients still have.” -Ahmed
The researchers believe that the next step will be to make contact with one of the companies that is in the midst of testing these drugs so that a trial of patients with Usher syndrome type 1F can be organized. In the more distant future, more research into the mechanism found in this study will be necessary to develop more significant therapies that can address the root cause by preventing retinal degeneration or slowing its progression.