Will BG-12 be neuroprotective and useful for Progressive MS?

The question of BLOGGERS is what interesting is going to appear act ECTRIMS 2012 next week. 

There is an expectation that the new drug BG-12 is going to be good news and we know about the results of the phase III trials. This will feature heavily at ECTRIMS next week as the results of the CONFIRM and DEFINE trials are reported. 


Whilst new MS reports are thin on the ground maybe some food for thought.

The question we are all interested to know is what would BG-12 do in progressive MS? Is there a trial planned?

There is clear data from the trials in RR MSers that BG-12 can inhibit the development of relapse, but there is real interest in whether this drug has additional neuroprotective effects. There is a clear inference that it does and is neuroprotective by an action on Nrf2 , which gives anti-oxidant activity. 

What happens in animal models? Well at doses of 100mg/kg/day in rodents it does have neuroprotective effects as was presented at ECTRIMS 2011. [p958] Arnold H et al Neuroprotective effects of BG-12 on malonate-induced striatal lesion volume in Sprague Dawley rat brain

This dose is more than used in human trials, at up to 250mg three times a day (750mg/day = 10mg/kg). At oral 15mg/kg these was a marginal inhibitory effect of the immune response in rodents suggesting more drug is needed.

Now is we use the 12.5 times rule, which is used to estimate human dose based on a dose in mice (12.5 times less) which has a more rapid metabolism of drugs than humans then we may be in the right dose range. But the poster at ECTRIMS was interesting because if indicated that BG-12 was over 90% excluded from the brain compared to the blood. Maybe accounting for the need to use whopping doses. 

If this is correct the drug does not reach the nerves much, so it would not be as good as it could as a neuroprotectant. The question that needs to known is what are the brain levels of the drug in MSers (This may be known?). This may give us an idea of whether it can be neuroprotective. If it is great, there may be ways to engineer the drug to get more into the brain for more effect. Food for thought.

CoI: Team G has recieved funds from Biogen the makers of BG-12 and Prof G is involved in clinical trials.

Labels: