Monitoring neuroaxonal loss in multiple sclerosis is an important objective to study the pathogenesis and response to treatment of the disease. The release of neurofilaments is a potential surrogate biomarker of neurodegeneration. One route to explore this aspect further is through the use of animal models that have well-defined, and predictable, disease courses.
The release of neurofilaments into plasma (blood) across the course of relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis in mice was assessed.
It was found that there was an immediate release in neurofilaments into the blood following the initial paralytic attack. Neurofilament release was continuous in relapse and remission but returned towards baseline in chronic disease, as animals entered the slowly developing post-relapsing progressive phase of the disease.
In contrast neurofilament levels increased dramatically as neurodegeneration and clinical disease occurred in the G93A SOD1 transgenic model of amyotrophic lateral sclerosis.
These data further support neurofilament levels as a good surrogate measure of neurodegeneration and their potential use as a surrogate endpoint in neuroprotective studies.
Green colour shows the neurofilament as an internal protein of the nerve. Red = glial cells
Progression of clinical disease occurs too slowly to undertake lots of clinicalt trials based on clinical features. Therefore we have we have been seeking indicators of disease worsening that can change quicker than clinical disability and so we could use those outcomes as surrogates to show disease activity. One thing we have found is neurofilament.
This is an internal part of the nerve and as nerves get damaged the nerves content is released first in to the cerebrospinal fluid and then into the blood. This study looked at two models of nerve damage, one that is known to occur by attacks of the immune system and another that is caused by neurodegenerative effects independent of autoimmunity. This study shows that with immune attack neurofilament can even be detected in the blood and tells us that stopping relapsing disease is a good thing. We know that each attack is indeed associated with nerve damage and that we can pick break down products of nerve attack in the blood supports this.
Next it says that in progressive MS models that slow progression that is independent of autoimmunity, such as secondary and primary progressive disease was not picked up in the blood in one model of neurodegeneration but was found in the blood in another model of neurodegeneration in a model that resembles motor neuron disease.
This tells us two things that measuring neurofilament release into biological fluids such as cerebrospinal fluid and the blood can give us an indication of the damage that is occuring in the central nervous system and that we may have to look in the cerebrospinal fluid rather than the blood.
Therefore if you have not watched the video and answered the survey on having three lumbar punctures as a method of detecting nerve damage and its control in a new trial disease design that will speed getting drugs to progressive MSers. Please watch the video and do the survey on the left. If you will not do it is just as important to know as if you will do it. These is no point in developing an idea that can not get off the ground
Are you up for having lumbar puncture
CoI: This is the work of Team G as part of Promse 2010