amaurosis (LCA) is an inherited retinal degenerative disorder that causes
starting in childhood. Two new studies published in the New England Journal of Medicine have
suggested that gene therapy for LCA improves patients' eyesight and sensitivity of the retina within weeks of
. These benefits peaked one to three years after treatment.
However, thereafter the effect began to diminish.
About 5-10% of people with LCA carry a mutated form of the
gene RPE65. The gene RPE65 normally makes an important protein found in the
retinal pigment epithelium (RPE), a layer of cells that nourish the light
sensors or photoreceptor cells of the retina It is needed for long-term
survival of photoreceptors. In persons' with LCA, these photoreceptor cells
eventually die, thereby resulting in vision loss.
studies havenow described the long-term follow-up of people with RPE65
LCA treated with gene therapy using sub-retinal injections of a virus designed to
produce healthy RPE65.
study, conducted in the United States, comprised of three patients with RPE65
LCA who were given a single extrafoveal sub-retinal injection of gene therapy
into one eye alone. The researchers observed that all three patients had
improvement in visual sensitivity in the treated region. This effect peaked at
one to three years after treatment. However, the visual sensitivity was found
to have declined thereafter for up to five to six years after the
treatment. The researchers noted that
despite the initial improvement in the treated eye, the retinal degeneration
continued at the same rate as in the untreated retina.
study, conducted in the United Kingdom, had enrolled 12 patients with RPE65
LCA and studied the effect of 2 doses of
. Researchers also
performed a similar study in dogs with naturally occurring RPE65 deficiencies. The 12 patients
were treated with similar gene therapy that relies on viral vectors as a means
to deliver the necessary gene. Six of the 12 treated patients had modest improvements
in visual sensitivities. This effect peaked at six to 12 months after the
therapy. However, the visual sensitivity again declined or was lost within
three or more years. Most
of the improvements were noted in the high dose group.
Both the study findings suggest that
without a highly efficient gene delivery system and sufficient surviving
retinal pigment epithelium and photoreceptors, gene replacement treatment
success for RPE65
-associated LCA lasts only for a short time. Also, it
may be possible to achieve stable and substantial restoration of vision as long
as gene replacement was performed at an early stage in the disease.