Developing gene therapy to prevent or delay sight loss in Bardet-Biedl syndrome

Research details

  • Type of funding: Project Grant
  • Grant Holder: Professor Phillip Beales
  • Institute: UCL Institute of Child Health
  • Region: London
  • Start date: December 2016
  • End Date: December 2018
  • Priority: Treatment
  • Eye Category: Inherited retinal


Bardet-Biedl syndrome (BBS) is an inherited disorder with a wide range of signs and symptoms including kidney disease and obesity. Sight loss starts in childhood due to cell death in the light-sensitive layer of the eye (the retina) and gets worse, leading to blindness in the teens.

Most people with BBS have a fault in a gene known as BBS1 (although 21 genes are known to cause BBS). In this study, the team aims to show that treatment with gene therapy can prevent or delay sight loss in mice with the same genetic fault and symptoms.

The team already has results showing the treatment is safe in healthy mice, and also have early results showing the treatment might work in BBS mice. This study is to find out more about when and how to give the treatment and how well it can work. The results are needed before human clinical trials can start, but that would be the next step if the results look good.
  • Scientific summary

    Adeno-associated virus mediated delivery of human BBS1 to the retina to rescue retinal degeneration in Bardet-Biedl syndrome

    Patients born with the inherited Bardet-Biedl syndrome (BBS) will experience a range of debilitating medical problems, some of which are life-limiting. Affected children have progressive loss of vision, from the first decade, which eventually leads to complete blindness. This is due to an advancing degeneration of photoreceptor cells in the retina. So far 21 genes have been found to cause BBS, BBS1 being the most frequently mutated gene in Northern Europe.

    The research team has designed a construct carrying the human BBS1 cDNA under a photoreceptor specific promoter, Rhodopsin-Kinase. An adeno-associated viral vector (AAV2/8.RK-BBS1) carrying the human BBS1 gene has already been successfully produced and injected at various doses underneath the retina in control mice. The team has seen widespread expression of their exogenous BBS1 transgene in the photoreceptor cells and importantly, observed no toxicity effects derived from the BBS1 overexpression.

    In the present project they aim to repair/prevent the retinal degeneration in a Bbs1 mouse model with the same BBS1 (M390R) mutation as carried by most patients. The BBS1 amino acid sequence it is highly conserved between human and mouse. Bbs1 M390R/M390R mutant mice present retinal degeneration with complete loss of the photoreceptors at 6 months, similar to BBS affected patients.

    Bbs1 M390R/M390R will be injected subretinally with the vector carrying the human BBS1 gene. The team will investigate the efficacy of this treatment for restoring/maintaining the vision of the mutant mice and on the survival of the retinal cells. Their first preliminary results show a recovery of retinal function in affected mice in the first month after treatment.