Case Western Reserve University researchers use lipids to safely deliver gene therapy to the eye, successfully holding off advance of rare, inherited eye disorder
Researchers at Case Western Reserve University have used a
unique method to safely deliver gene therapy to fight a rare, but irreversible,
genetic eye disorder known as Stargardt disease.
By using chemically modified lipids—instead of the viruses
most commonly used as carriers—Stargardt
disease did not return in animal models for up to eight months after treatment,
said lead researcher Zheng-Rong Lu, the M. Frank Rudy and Margaret Domiter Rudy Professor
of Biomedical Engineering at the Case School of Engineering, with a
dual appointment at the School of Medicine.
“This grant provides innovative scientists like Dr. Lu both funding and drug development expertise to advance research that will defeat diseases that limit millions of people from experiencing the gift of sight,” said Jonathan S. Stamler, president of Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation at University Hospitals and professor of medicine and biochemistry at Case Western Reserve University School of Medicine. “It is very encouraging to see Dr. Lu’s work move closer to human trials.”
A so-far incurable
The research may
give some hope to people with Stargardt disease, an inherited
disorder of the retina also known as “macular dystrophy” or “juvenile macular
degeneration” because it often surfaces during childhood or adolescence.
Although individuals with Stargardt disease rarely go
completely blind, they progressively lose vision in both eyes, become very
sensitive to light and, in some cases, develop color blindness.
“We’re really excited because there is a potential to help
people with Stargardt,” Lu said. “But we believe this success could also apply
to other disorders as a platform therapy for delivering other genes through the
use of the lipids.”
Lipids are simple organic
compounds, or fatty acids, that are insoluble in water, including various natural oils, waxes and steroids.
“Because they are
basically unsaturated oil, the likelihood of damage to the eye is low, which
isn’t always true with the viral gene therapy,” Lu said.
Gene therapy offers
“There are a lot of researchers trying to figure out how to
treat this disease right now with little success,” Lu said. “The best hope is
Gene therapy is the
technology in which genetic
material is introduced into cells by an engineered carrier to compensate for
abnormal genes or to make a
The most successful gene therapy carriers
so far have been certain viruses (the AAV, or adeno-associated virus,
especially) because they can deliver the new gene
by “infecting” the target cell.
But the Stargardt-associated gene, known as the ABCA4 gene, turns out to be too large to
fit within that popular virus, Lu said.
Lu said other researchers have attempted to remedy that
problem by splitting ABCA4 into pieces and then trying to reassemble it
inside the eye—with limited success.
Other researchers have modified a larger virus to carry
ABCA4 into the eyes, a technology tested in human trials as far back as 2011,
but which still hasn’t been fully commercialized.
He said he and his
collaborators have also already met with investors to expedite the
commercialization of the platform used for Stargardt.
Further, this gene therapy product could be classified as
an “orphan drug” by the U.S. Food and Drug Administration (FDA) because
Stargardt is a rare disease, increasing the likelihood of faster FDA approval after
clinical trials, Lu said.
The non-viral gene therapy is also much more
cost-effective for production than the virus-based therapy and has a potential
to significantly reduce the high price of gene therapy in the eye, he said.
“We think that within two to three years we could really be helping people after further demonstration of its safety and efficacy,” Lu said.