• Drug 'cocktail' could restore vision in optic nerve injury

    From Fenris@21:1/5 to All on Sat Jan 16 10:42:50 2016
    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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