Age-Related Macular Degeneration Treatment with Gene
Therapy Shows Promise
AMD results in a loss of sharp, central
vision; number one cause of visual impairment among Americans age
60 and older
April 29, 2011 A gene therapy approach using a
protein called CD59, or protection, shows promise in slowing the signs
of age-related macular degeneration (AMD), according to a new study
from Tufts University School of Medicine.
Led by senior author Rajendra Kumar-Singh, PhD, the
researchers, using mice, demonstrated for the first time that CD59
delivered by a gene therapy approach significantly reduced the
uncontrolled blood vessel growth and cell death typical of AMD. AMD is
the most common cause of blindness in the elderly.
Activation of the complement system, a part of the
immune system, is responsible for slowly killing cells in the back of
the eye, leading to AMD. Activation of this system leads to the
generation of pores or holes known as 'membrane attack complex' or MAC
in cell membranes. CD59 is known to block the formation of MAC.
"CD59 is unstable and hence previous studies using
CD59 have had limited success. The gene therapy approach that we
developed continuously produces CD59 in the eye and overcomes these
barriers, giving us renewed hope that it can be used to fight the
progression of AMD and potentially other diseases," said Kumar-Singh.
Kumar-Singh is associate professor in the
department of ophthalmology at Tufts University School of Medicine (TUSM)
and member of the genetics; neuroscience; and cell, molecular, and
developmental biology program faculties at the Sackler School of
Graduate Biomedical Sciences at Tufts.
Kumar-Singh and colleagues delivered CD59 to the
eye using a deactivated virus similar to one previously shown to be safe
in humans. Using an established mouse model of age-related macular
degeneration, they found that eyes treated with CD59 had 62 percent less
uncontrolled blood vessel growth and 52 percent less MAC than controls.
"Treatment was effective when administered at a
very specific location beneath the retina, but importantly, also when it
was administered to the center of the eye. This finding is especially
encouraging because it would allow for a safer and more convenient route
of administration of treatment," said co-first author Siobhan Cashman,
PhD, assistant professor in the department of ophthalmology at Tufts
University School of Medicine and member of Kumar-Singh's lab.
The current standard treatment for some forms of
AMD requires an injection directly into the eye approximately every four
weeks. According to Kumar-Singh, gene therapy approaches to treat AMD
are especially attractive because they will allow patients to be treated
less frequently, reducing patient discomfort and lowering chances of
infection and other side effects associated with frequent injections
into the eye.
The researchers, including co-first author Kasmir
Ramo, BS, research technician, believe that while CD59 has significant
potential as a treatment for AMD, the gene therapy approach lends itself
for application also in other eye and systemic disorders where low-level
activation of complement has been implicated.
"Prior to initiating human clinical trials, we will
need to perform extensive preclinical toxicology studies. In order to
advance this study to Phase I clinical trials, we have formed a
partnership with Hemera Biosciences Inc. to raise private venture
capital," said Kumar-Singh.
AMD, which results in a loss of sharp, central
vision, is the number one cause of visual impairment among Americans age
60 and older. While treatments are available for wet AMD, they do not
prevent the progression of dry AMD, the form that affects 90 percent of
Kumar-Singh noted, however, that the current study
in combination with a previously published study from his laboratory
suggests that CD59 may be useful for the treatment of both the dry and
wet forms of AMD.
The study was published on April 28 in PLoS ONE.
This study was supported by grants from The Ellison
Foundation; the National Eye Institute, part of the National Institutes
of Health; the Virginia B. Smith Trust and grants to the department of
ophthalmology at TUSM from the Lions Eye Foundation and Research to
Reference: Cashman SM, Ramo K, Kumar-Singh
R. PLoS ONE. "A Non Membrane-Targeted Human Soluble CD59 Attenuates
Choroidal Neovascularization in a Model of Age Related Macular
Degeneration." Published online April 28, 2011,
About Tufts University School of Medicine and
the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler
School of Graduate Biomedical Sciences at Tufts University are described
as international leaders in innovative medical education and advanced
research. The School of Medicine and the Sackler School are renowned for
excellence in education in general medicine, biomedical sciences,
special combined degree programs in business, health management, public
health, bioengineering and international relations, as well as basic and
clinical research at the cellular and molecular level. Ranked among the
top in the nation, the School of Medicine is affiliated with six major
teaching hospitals and more than 30 health care facilities. Tufts
University School of Medicine and the Sackler School undertake research
that is consistently rated among the highest in the nation for its
effect on the advancement of medical science.
About Macular Degeneration
called: Age-related macular degeneration, AMD
Macular degeneration, or age-related macular degeneration (AMD) is a
leading cause of vision loss in Americans 60 and older. It is a disease
that destroys your sharp, central vision. You need central vision to see
objects clearly and to do tasks such as reading and driving.
affects the macula, the part of the eye that allows you to see fine
detail. It does not hurt, but it causes cells in the macula to die. In
some cases, AMD advances so slowly that people notice little change in
their vision. In others, the disease progresses faster and may lead to a
loss of vision in both eyes. Regular comprehensive eye exams can detect
macular degeneration before the disease causes vision loss. Treatment
can slow vision loss. It does not restore vision.