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Project 6
Multiple sclerosis: use of low level naltrexone delivered via slow release implants as a possible treatment optionMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the CNS manifested by damage to and loss of myelin as well as neuronal death. Optic neuritis and degradation of visual function is one of the most common and early clinical manifestations. A widely used laboratory rodent model of MS is experimental allergic encephalitis (EAE) in which injection of myelin proteins such as myelin basic protein or myelin oligodendrocyte glycoprotein induce demyelination (1); Lewis (EAE-susceptible) rats are the strain of choice. In EAE, immune-mediated attack of myelin within the optic nerve follows a well characterized and rapid time-course with loss of myelin and RGCs as early as one week as well as other changes such as loss of visual acuity and a breaching of the blood brain barrier (2). To date there are no long term successful treatments for MS. However, the use of low doses of naltrexone, an opiate receptor antagonist, for the treatment of MS enjoys a worldwide following amongst patients since it not only prevents relapses but also reduces the disease progression. Nevertheless, available evidence supporting such a practice is largely anecdotal and experimental as well as clinical work is clearly warranted (3). This project will investigate the effects of low levels of naltrexone delivered via subcutaneous slow release implants. Such implants have been developed by a Perth company, GoMedical, and are currently used clinically in Perth to treat heroin addiction. Adult Lewis rats will be implanted with either an active or placebo naltrexone implant. Once naltrexone levels have stabilized (~8 days), EAE will be induced and disease progression monitored on a daily basis using standard clinical diagnosis. A number of clinical signs, such as hind limb paresis, are manifest within 1 week. Animals will undergo functional testing using ERG and sacrified for histological analysis. The extent of myelination within the optic nerve will be quantified using light and electron microscopy. RGC loss will be determined from retinal wholemounts.
  
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