I can't support this with any direct citations, but I'm beginning to wonder if type 2 Narcolepsy may have an entirely different etiology than type 1. For example, we don't typically see in type 2 N the wholesale destruction of orexin neurons like we do in type 1. So obviously a substantial population of orexin neurons are there, but something is seems to be blocking or countering orexinergic transmission. Although the presentation of symptoms appears similar with the major difference being the presence of cataplexy in type 1 N, anecdotal evidence derived from sustained conversation with narcoleptics reveals that persons with type 2 N often don't experience the full cluster of symptoms classically associated with N, with many experiencing only EDS.

The question I'm most curious about is whether or not the actions of dynorphin, neurotensin, NARP. VGLUT2 and DLK-1 (did I miss any?) all of which are co-localized on orexin neurons, are also affected in type 2 (obviously in type 1 where the neuron is gone, they are no longer expressed).  Perhaps in type 2 N some other process such as GABAergic inhibition of orexin transmission is the culprit and not the autoimmune reaction presumed to result in the cluster of symptoms called type 1 N?  In which case everything else should be working?

Do you know of any research that has compared the difference in TOTAL neuroprotein etc. expression between type 1, type 2 and healthy controls to determine what the effect is of the loss of all of those neurochemicals? 

For example, there was an article in the press today showing that Ox modulates HT-5's regulation of respiration.  In type 1 N the dysmodulation should be more apparent than it is in type 2 N.  Is it?  That kind of thing.

I would think this avenue of inquiry is especially important  for those working on Ox receptor agonists.  For folks with type 1 N, would that be enough?  The neurons are gone so those other things still aren't going to be produced.  Does that matter?

ANy light anyone can shed on this would be appreciated.