Looking at 160 people with the mutation that go to a sleep lab is not a good way to find out whether there are negative effects of a gene. Instead of solving that problem in a sleep lab it makes sense to look at huge genomic databases such as the UK biobank to study the effect of the genetic mutation.
For those who want to work towards developing a drug, there are various paths of advancement. For example, with DEC2, one could check (first in mice) if administering orexin (which can be done with nasal spray[4]) at the right dose and schedule has the same effect as having mutant DEC2; if so, that could be the drug.
I would expect that orexin does not cross the blood-brain barrier.
So. I’m trying to tell people about this trillion-dollar bill lying on the sidewalk. Who’s going to pick it up?
The researchers at Takeda tried. They found an orexin agonist and ran it through clinical trials and the FDA gave them Breakthrough Therapy status last year:
The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to TAK-994 for the treatment of excessive daytime sleepiness in patients with narcolepsy type 1.
They ran into some trouble with their trial but there’s hope:
After Takeda stopped trials of TAK-994 last year the future for treating narcolepsy with orexin-2 agonists looked bleak. But hopes were rekindled yesterday when Jazz endorsed the approach with a $50m up-front payment to Sumitomo Pharma to license the latter’s DSP-0187. The companies describe DSP-0187, which recently entered phase 1 in Japan, as a highly selective oral agent, and perhaps the hope is that selectivity will circumvent the toxicity signal that appeared to trip up TAK-994 in phase 2.
You likely won’t get FDA approval for a drug that reduces healthy people’s sleep needs by an hour. Focusing the drug development on narcolepsy makes a lot of sense to get the drug approved. Ideally, it will become a drug that’s easy to use off-label but that will depend on a lot of factors.
Looking at 160 people with the mutation that go to a sleep lab is not a good way to find out whether there are negative effects of a gene. Instead of solving that problem in a sleep lab it makes sense to look at huge genomic databases such as the UK biobank to study the effect of the genetic mutation.
I would expect that orexin does not cross the blood-brain barrier.
The researchers at Takeda tried. They found an orexin agonist and ran it through clinical trials and the FDA gave them Breakthrough Therapy status last year:
They ran into some trouble with their trial but there’s hope:
You likely won’t get FDA approval for a drug that reduces healthy people’s sleep needs by an hour. Focusing the drug development on narcolepsy makes a lot of sense to get the drug approved. Ideally, it will become a drug that’s easy to use off-label but that will depend on a lot of factors.