| In 2003 Dr Miguel Che Parreira Soares from the Instituto Gulbenkian de Ciência, Oeiras, Portugal was awarded a GEMI Fund grant for research into ‘The regulatory effect of carbon monoxide in the pathogenesis and remission of multiple sclerosis’.
As the clinical progression of multiple sclerosis (MS) is in most cases associated with transitory periods of disease remission, it was suggested that there must be some sort of mechanism that calms the neuroinflammation and/or promotes neuron regeneration. Dr Soares hypothesized that a cytoprotective and anti-inflammatory gene, known as heme-oxygenase-1 (hmox1/HO-1), could act in this way.
The research set out to establish whether HO-1 and/or CO prevent the development of an animal model of multiple sclerosis, to indicate whether human Multiple Sclerosis might possibly behave the same way. The animal model is called Experimental Autoimmune Encephalomyelitis (EAE). The research also set out to see whether HO-1 and/or CO could actually prevent EAE development.
The research data suggests that HO-1 can in fact control the pathologic outcome of EAE. In addition to stopping the progression of EAE, induction of HO-1 resulted in complete disease remission in 70% of mice with established EAE. Mice were also exposed to CO at concentrations of 450 parts per million, via inhalation, to see if this had a similar effect to HO-1. The effect of CO was compared to that of air, inhaled under similar flow conditions. Inhaled CO reduced EAE progression and severity almost as well as HO-1 and a significant protective effect was also observed when lower levels of CO (250 ppm) were applied.
Dr Soares expresses necessary caution in extrapolating from these findings and making inferences from the animal model EAE to human Multiple Sclerosis. Nonetheless, if it is assumed that MS represents a prototypical inflammatory disease, the results suggest that HO-1 could counter the deleterious effects of neuroinflammation that are part of the progression of multiple sclerosis. Dr Soares therefore suggests that modulation of HO-1 expression, or the administration of CO, could be used therapeutically to suppress the pathogenesis of MS. |
