Nathoo N, Yong VW, Dunn JF. Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis.Mult Scler. 2013 Nov 21. [Epub ahead of print]
Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics.
There has been a failure to translate many animal studies into human benefit. Some of these failures may have because the MRI outcomes measures used in trials were either sensitive enough, they did not detect pathologically/clinically meaningful outcomes as anticipated. For example in the Lamotrigine trial the outcome measure was CNS atrophy and the drug treatment appeared to make atrophy occur at a faster rate than the placebo. Was this because it made the MSers lose more nerves?. However once treatment stopped the size of the CNS became bigger so it was hardly nerves re growing. Maybe there was swelling due to MS and the drug had anti-inflammatory effects and got rid of the swelling? We cannot know what really happened because we could not view the tissues. In animal studies one could and maybe work out what MRI outcomes are really measuring. The problem is the degree of resolution as the CNS of animals is much smaller than a human brain, but with even more powerful MRI machines amazing images are achievable. It would be great to perform imaging in all animal studies, but it will mean that millions have to be found to purchase and maintain the scanners if this was uniformly used. Also it is important that scanners can image the spinal cord, which is more difficult, because of breathing making the spinal cord move, and not just the brain, because in most cases the neurological deficits are because of spinal cord involvement.