UCL Institute of Ophthalmology Department of Genetics
Gene therapy for Leber congenital
amaurosis (LCA) caused by damage to the
RPE65 gene
We conducted the world’s first clinical trial assessing the
safety and efficacy of viral gene therapy for inherited
sight loss (Bainbridge et al 2008)
Leber congenital amaurosis and the
RPE65 gene
• LCA is a severe inherited retinal disease in which vision is
affected from birth and continues to worsen in early adulthood,
leading to complete blindness
• RPE65 is one of many genes associated with LCA
• Damage to the RPE65 gene means that retinal pigment
epithelium (RPE) cells underlying the light-sensitive
photoreceptor cells cannot recycle the visual pigment used to
detect light
Why was LCA caused by damage to
RPE65 the first eye gene therapy trial?
• The genetic cause of the disease is well understood
• Although vision is affected early in life and worsens over time,
photoreceptor cells remain healthy in the early stages of
disease so they can be targeted by gene therapy vectors
• We have established proof-of-principle that RPE65 gene
replacement restores vision in small and large animal models
• The intervention might improve visual function rather than just
slow sight loss
RPE65 clinical trial – surgical procedure
• Key hole surgery is used to pass a fine probe into the vitreous
jelly at the back of the eye
• The virus suspension is then injected underneath the retina,
causing a temporary elevation of the retina – this detachment
usually disappears the following day
• Recovery from gene therapy surgery is similar to other types of
retinal surgery, and patients can normally return to normal
activities within 2 weeks
Improvements in vision following
gene therapy
• Several patients have shown improvements in visual function
with a variety of tests
• Patients have shown improved peripheral vision when tested
under dim lighting conditions (shown by the green bars)
Improvements in vision following
gene therapy
• Patients have shown improvements in their central vision
when tested with light stimuli to the central retina (shown by
the white circles below)
Improvements in vision following
gene therapy
• Some patients have also
shown improvements in
their ability to navigate
through an obstacle course
in dark conditions, showing
that improvements can be
useful in day to day
navigation
Improved night vision following gene therapy
Conclusions and future plans
• Retinal gene therapy is safe to perform in the eye
• Results so far suggest that it can improve visual
function
• The success of this trial for LCA paves the way for gene
therapy trials for many other types of retinal diseases