Developing therapies for severe forms of rhodopsin retinitis pigmentosa

Brief plain language background 

Inherited genetic changes are a major cause of blindness in the working-age population. These conditions can be passed on from one or both parents. When passed on from just one parent, it is called dominant disease (meaning one copy of the changed gene is enough to cause disease).

Changes in the rhodopsin gene (RHO), which makes a light-sensitive protein needed for vision in the dark, are the most common cause of dominant inherited blindness. Night vision is lost first, followed by gradual loss of daytime vision.

The most common RHO change in the UK causes a severe, fast-progressing form of retinitis pigmentosa (RP). This change, called P347L, is a small “spelling mistake” in the gene that alters the protein. This project will investigate how this causes disease and test potential therapies.

What problem/knowledge gap does it help address?

Although P347L is a common disease-causing change, we do not fully understand how it causes damage. There are no approved treatments for harmful RHO changes.

Therapies for another change (P23H), currently in clinical trials, will not work for P347L because it damages cells differently. This study will test therapies specifically for P347L, with potential relevance to other inherited vision loss conditions.

Aim of the project

The project will test therapies to block the harmful effects of the mutation, either by targeting the genetic change or reducing the faulty protein. It will also explore whether altering how photoreceptor (light-sensing) cells use energy can prevent damage.

Potential impact on people with sight loss

This work could lead to treatments for patients who currently have no options. Testing in mouse and human models may speed up progress to clinical trials.

Recent patient studies have improved understanding of disease progression and trial design. If successful and funded, a clinical trial could begin within 3–5 years after the project ends.