Planning a gene therapy clinical trial for X-linked retinitis pigmentosa

Research details

  • Type of funding: Project Grant
  • Grant Holder: Professor Michel Michaelides
  • Institute: UCL Institute of Ophthalmology
  • Region: London
  • Start date: October 2015
  • End Date: March 2019
  • Priority: Early detection
  • Eye Category: Inherited retinal


X-linked retinitis pigmentosa (XLRP) is a severe inherited condition that leads to legal blindness by age 40. Symptoms start with night blindness, usually before the age of 10 and progress to losing peripheral (side) vision and finally central, detailed vision.

XLRP is due to a fault on the X chromosome, usually in a gene named RPGR. At the moment there is no cure, but researchers are planning to do clinical trials of gene therapy in the next 3-5 years. The idea is to engineer a safe virus to carry a healthy version of the gene into cells, replacing the faulty gene.

So in this study the team is collecting the information they need to plan the clinical trial well. They are following 60 people with XLRP due to a faulty RPGR gene for 3 years. The aim is to find out about how the exact genetic fault each individual has affects how their XLRP develops. For example, do some faults mean the condition progresses faster?

At the end of the project the team should have a clear idea of which people could benefit most from gene therapy. They’ll also know more about when the best time for treatment is and about the most useful ways to measure whether the treatment is working. The results will also help patients to have better genetic counselling about how the condition might affect them and their family.

  • Scientific summary

    Assessing photoreceptor structure and function in X-linked RP associated with RPGR mutations using in-depth advanced phenotyping in preparation for planned therapeutic intervention.

    In preparation for planned gene replacement clinical trials in RPGR-associated retinitis pigmentosa (by this group led by Professor Robin Ali, and other groups around the world), which are anticipated in the next 3-5 years, the team is undertaking a detailed longitudinal clinical study with serial assessments of genetically proven patients.

    The aims of this study include: to identify patients who may be most suitable for therapeutic intervention; to establish the natural history and rates of progression; to identify the window of opportunity to intervene; and to determine the most sensitive and accurate measures of treatment effect.

    These aims are being achieved by using cutting-edge deep phenotyping technology to undertake structural and functional assessments including adaptive optics imaging and advanced analysis of retinal sensitivity measurements. This in-depth translational clinical study is a fundamental prerequisite to treatment trials being initiated.