Targetting Nogo A as a means to promote CNS axonal regrowth

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/380832

Funding Status
Closed

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Funded Activity Summary

Unlike the peripheral nervous system, regenerative nerve fiber growth and structural plasticity are limited in the adult mammalian central nervous system (CNS), following injury. Although lesioned axons can sprout spontaneously, this regeneration attempt is transitory and no significant re-growth occurs over long distances. Consequently, injury to the CNS often leads to permanent disability. In many cases, it has been shown that it is not the absence of growth-promoting molecules in the CNS but rather the presence of axon outgrowth inhibitors, including components of both CNS myelin and astroglial scars that limit regeneration. Given that axonal injury is an important pathological determinant of permanent disability in multiple sclerosis (MS), we have recently investigated the role of the CNS neurite outgrowth inhibitor, Nogo A in the development of a chronic form of murine MS-like disease. We showed that targeting Nogo A by active and passive immunization blunts clinical signs, demyelination and axonal damage associated with this model of MS. These results identify Nogo A as an important determinant of the development of autoimmune-mediated demyelination and suggest that its blockage may help to maintain and-or to restore the neuronal integrity of the CNS after autoimmune insult in disease such as MS. The principal goal of this application is to study the mechanism by which blockade of Nogo A improves clinical outcome in disease like MS and to determine whether neurite sprouting accounts for such an improvement. Targeting Nogo A and-or its receptor, has the potential to not only regulate-modulate the process of autoimmune mediated demyelination but could lead to the first therapy ever offered to patients that helps damaged nerves regenerate after axonal injury following neurodegeneration due to insult or disease.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $325,911.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cell Neurochemistry

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Central nervous system demyelination and inflammation | Neurological disorders | mechanisms of neuronal degeneration and the role of p75NTR | myelin | nerve regeneration | neurite outgrowth | neurodegeneration | neurodegenerative and age related diseases | spinal cord injury

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