http://www.medicalnewstoday.com/releases/305146.php


Drug 'cocktail' could restore vision in optic nerve injury
Adapted Media Release
Published: Today


Research from Boston Children's Hospital suggests the possibility of
restoring at least some visual function in people blinded by optic nerve
damage from glaucoma, estimated to affect more than 4 million Americans,
or from trauma.

As reported online January 14 by the journal Cell, the scientists
restored vision in mice with optic nerve injury by using gene therapy to
get the nerves to regenerate and -- the crucial step -- adding a channel-blocking drug to help the nerves conduct impulses from the eye
to the brain. In the future, they believe, the same effect could be
achieved with drugs alone.

In the study, previously blind mice turned their heads to follow
patterns of moving bars after given the treatment, say co-senior
investigators Zhigang He, PhD, and Michela Fagiolini, PhD, of the
Department of Neurology and F.M. Kirby Neurobiology Center at Boston Children's. The technicians doing the tests did not know which mice had
been treated.

"By making the bars thinner and thinner, we found that the animals could
not only see, but they improved significantly in how well they could
see," says Fagiolini.

While other teams, including one at Boston Children's, have restored
partial vision in mice, they relied on genetic techniques that can only
be done in a lab. Generally, their methods involved deleting or blocking
tumor suppressor genes, which encourages regeneration but could also
promote cancer. The new study is the first to restore vision with an
approach that could realistically be used in the clinic, and that does
not interfere with tumor suppressor genes.
Getting nerves to conduct

The key advance in restoring vision was getting the regenerated nerve
fibers (axons) to not only form working connections with brain cells,
but also to carry impulses (action potentials) all the way from the eye
to the brain. The challenge was that the fibers regrow without the
insulating sheath known as myelin, which helps propagate nerve signals
over long distances.

"We found that the regenerated axons are not myelinated and have very
poor conduction -- the travel speed is not high enough to support
vision," says He. "We needed some way to overcome this issue."

Turning to the medical literature, they learned that a potassium channel blocker, 4-aminopyridine (4-AP), helps strengthen nerve signals when
myelin is absent. The drug is marketed as AMPYRA for multiple sclerosis,
which also involves a loss of myelin. When they added it, the signals
were able to go the distance.
A paradigm for treating glaucoma and optic nerve injury

While the study used a gene therapy virus called AAV to deliver the
growth factors that trigger regeneration (osteopontin, insulin-like
growth factor 1 and ciliary neurotrophic factor), He and Fagiolini are
testing whether injecting a "cocktail" of growth factor proteins
directly into the eye could be equally effective.

"We're trying to better understand the mechanisms and how often the
proteins would have to be injected," says He. "The gene therapy virus we
used is approved for clinical study in eye disease, but a medication
would be even better."

With regeneration kick-started, 4-AP or a similar drug could then be
given systemically to maintain nerve conduction. Because 4-AP has
potential side effects including seizures if given chronically, He and Fagiolini have begun testing derivatives (not yet FDA-approved) that are potentially safer for long-term use.

The researchers are further testing the mice to better understand the
extent of visual recovery and whether their approach might get myelin to
regrow over time.

"The drugs might need to be paired with visual training to facilitate recovery," says Fagiolini. "But now we have a paradigm to push
forward."
--
Fenris

The SHG for RSPCA Problems Blog
http://theshg.wordpress.com

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