Developing gene therapy for autosomal recessive bestinopathy

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Robert MacLaren
  • Institute: University of Oxford
  • Region: South East
  • Start date: October 2013
  • End Date: September 2016
  • Priority:
  • Eye Category:


Gene therapy has great potential to treat many types of inherited eye conditions that are currently incurable. One condition that could be relatively easy to develop gene therapy for with current technology is a type of Best disease called autosomal recessive bestrophinopathy (or ARB). It’s caused by faults in the BEST1 gene and involves slow loss of central vision.

In this project the PhD student is aiming to develop gene therapy for ARB by using an engineered virus to carry a healthy version of the gene into a part of the eye called the retinal pigment epithelium. This is a layer of cells that support and nourish the light-sensitive cells in the retina. BEST1 has the instructions for making a protein called bestrophin, which is found in the support cell layer and is vital for normal vision. The virus has already been used safely in clinical trials for other inherited eye disorders. Results from this study, which is being done in mice with Best-like symptoms and in human cells, should provide the data that’s needed before human clinical trials can be approved.
  • Scientific summary

    Developing gene therapy for Best Disease

    Gene therapy will almost certainly become a viable treatment for many currently incurable forms of blindness in future years. At present gene therapy technology limits effective treatment to patients who have loss of function mutations in relatively small genes that are ideally expressed in the retinal pigment epithelium (RPE). Consequently all five gene therapy clinical trials so far have targeted relatively rare conditions that fulfil these criteria: in addition to gene therapy trials for Leber’s congenital amaurosis due to mutations in RPE65, Professor MacLaren is also leading a gene therapy trial for choroideraemia. The recessive form of Best disease also fulfils these criteria and would present another ideal condition to treat with gene therapy.

    This studentship involves a series of experiments to generate and test a viral vector suitable as a potential treatment to be assessed in a clinical trial for this condition. The research plan compares the relative strengths of an RPE-specific- to a ubiquitous promoter in a viral vector and assesses the bestrophin protein in the Best1 knockout mouse and in human cells in vitro with regard to membrane conductance. Collectively these experiments are exactly what the regulatory authorities - the Gene Therapy Advisory Committee (GTAC) and the Medicines and Healthcare products Regulatory Authority (MHRA) - would require for a clinical trial approval. The high translational focus of this project is ideally suited to train a PhD student in developing the necessary skills to pursue vision related eye research for patient benefit.