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Where's My Hypocretin/orexin Nasal Spray?


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#1 severianthegreat

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Posted 23 October 2011 - 02:29 AM

It's been almost four years since the Wake Forest University Hypocretin/Orexin Nasal Spray study done on primates. Has anyone heard of any real developments on this for US Narcolepts?

All current treatments make some symptoms more bearable, but none really address the root issue or enable narcolepts to live normal lives. Given that Hypocretin/orexin replacement therapy would seem to treat the root problem (hypocretin/orexin deficiency) and that the study indicated a nasal spray is more effective than even intravenous delivery, it's a little surprising that there have been no further studies or developments for human treatments in the past four years.

Have you heard of this treatment? Is there any word on its development? Are there any doctors or pharmocological experts who can speak to this? Are there any other narcolepts holding out hope for this treatment?

I live a restrictive, isolated life on 400mg of Provigil daily. My only hope of one day being truly awake is real treatment.

Eric

#2 tdmom

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Posted 24 October 2011 - 08:47 PM

My sons neurolgist said he was at a conference in Germany this summer and it is in trials there. He seemed to find it promising. Maybe I will call the library at the medical center where I work and see if they can find something on it. My son is on 400 mg Provigil a day (200 x 2), Prozac and he just started Xyrem. This would be a godsend.

#3 severianthegreat

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Posted 25 October 2011 - 11:23 PM

thanks tdmom - that would be awesome!

I think I might also try to email/contact the contributors to the study and see if they know of anything in the works.

On a related note, OHSU did a study on why sick people feel 'bad' found it was due to low hypocretin. And they were able to make sick mice act like normal mice by dosing them with hypocretin. This study was done earlier this year. I couldn't get the full article, but you can read about the study on OHSU's site at Why Sick People Feel Bad. However, it's unclear on if they want to treat sick people with current narco meds or ones that are being developed.

#4 Chippervan

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Posted 26 October 2011 - 07:14 AM

i am on the same quest. something interesting i found through a link on the wikipedia page on Orexin A in the references section:

4. ^ Denis Burdakov et al. (31 May 2006). "New mechanism explains glucose effect on wakefulness". Neuron. Retrieved 2008-01-25.


excerpt from article: experiments showed that glucose inhibits orexin neurons by acting on a class of potassium ion channels known as "tandem pore" channels, about which little was known.

does this mean that glucose is bad for narcoleptics?

i will research the hypocretin/orexin nasal spray.

also, i don't think this is the only possible treatment route. some sort of neuromodulation type device could also help. possibly by controlling our sleep.

#5 sometimes

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Posted 27 October 2011 - 02:00 AM

It's been almost four years since the Wake Forest University Hypocretin/Orexin Nasal Spray study done on primates. Has anyone heard of any real developments on this for US Narcolepts?

All current treatments make some symptoms more bearable, but none really address the root issue or enable narcolepts to live normal lives. Given that Hypocretin/orexin replacement therapy would seem to treat the root problem (hypocretin/orexin deficiency) and that the study indicated a nasal spray is more effective than even intravenous delivery, it's a little surprising that there have been no further studies or developments for human treatments in the past four years.

Have you heard of this treatment? Is there any word on its development? Are there any doctors or pharmocological experts who can speak to this? Are there any other narcolepts holding out hope for this treatment?

I live a restrictive, isolated life on 400mg of Provigil daily. My only hope of one day being truly awake is real treatment.

Eric


I think we're all waiting and hoping for Orexin. It would certainly much much more novel than modafinil.

#6 Chippervan

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Posted 27 October 2011 - 04:35 AM

I think we're all waiting and hoping for Orexin. It would certainly much much more novel than modafinil.


a good way to look up current research is to find a good article and then find articles that cite that article.

i'm busy checking through articles that have cited an article i found through the orexin-a wikipedia website:

i.e. Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

by finding articles that cite this article you can hopefully get to the most recent studies

here is something from german researchers (possibly linked to what TDmom said): Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1). THIS WAS ON HUMANS!!!!! and it dates back to 2008.

YOU SAID SOMETHING ABOUT EMAILING THE GUY, here are his details:
Correspondence to: Paul Christian Baier, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, 24105 Kiel, Germany E-mail: p.baier@zip-kiel.de

i'm quiet busy till monday so maybe you can email him. probably best not to bombard him. if you don't have time, i'll e-mail him on Monday.

also, i think it is not only having this neurotransmitter as a drug that will help. i think by knowing exactly what it does we can get a better understanding of the impact of narcolepsy and hence can find alternative behaviours to overcome these shortcomings. (that said, hopefully that won't matter and a drug will be out soon)
anyways, here's a related article:

Highly Specific Role of Hypocretin (Orexin) Neurons: Differential Activation as a Function of Diurnal Phase, Operant Reinforcement versus Operant Avoidance and Light Level

#7 severianthegreat

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Posted 27 October 2011 - 08:41 AM

Chippervan,

Thank you for the information and research tips! I've been in email contact with Siegal, who worked on the 2007 hypocretin nasal spray study and also on the one you mention at the end of your post regarding light avoidance that's being published this month. Unfortunately, he knows of no clinical or commercial research being done in the US to develop treatment, though he did express that he had similar hopes.

Thank you for bringing the 2008 German study on humans to everyone's attention! As you've suggested, I've gone ahead and emailed Dr. Baier and will let everyone know once I hear back. And I've also reached out for Dr. Marks of the OHSU study I mentioned previously as he indicated on their website that drugs mimicking hypocretin might be in the works.

The OHSU study has other implications as well, namely that this type of treatment could potentially benefit cancer, Parkinson's, and other communities whose illnesses are often fatal or long term. For those communities, it would likely only help improve symptoms, but our own experiences show that even that is a huge benefit. I believe that if it's true that nothing is currently being developed, that partnering with other such communities could have great potential.

If anyone else uncovers anything, please post!

#8 severianthegreat

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Posted 01 November 2011 - 12:25 AM

Disclaimer: While I identified myself as part of the narcolepsy community asking for my and others' benefit, I did not ask permission to cite any of the doctors. Please limit references to the doctors' opinions to the forums or private communications.

All,
The last few days have been very exciting - I've been in contact with Dr. Siegal, Dr. Marks, and just today with Dr. Baier.

The Researchers Note: I've only attempted to contact one doctor from each study, each study had other doctors involved.
Dr. Jerome Siegal:

Worked on the original 2007 Hypocretin Nasal Spray study using rhesus monkeys and the 2011 Hypocretin's Role on Working in Light vs Dark, from this month. He expressed his belief that it has a lot of potential as a possible treatment for narcolepsy and Parkinson's.

Dr. Daniel Marks:

Worked on the 2011 Illness Related Lethargy Due to Low Hypocretin study (aka Why Sick People Feel Bad study) studying humans and using mice to test treatments. His study isn't about narcolepsy at all, but could prove critical in developing treatment by getting other communities involved, like those for cancer, Parkinson's, etc.

Dr. Paul Baier:

Worked on two studies that used humans with narcolepsy; the 2008 Hypocretin Nasal Spray's Effect on Olfactory Senses and the 2011 Hypocretin Nasal Spray's Effect on REM Sleep, which was just published today! He also expressed a strong belief that this treatment has great potential.

The Studies
2007 Hypocretin Nasal Spray using Rhesus Monkey's (Dr. Siegal):

Introduced the nasal spray treatment and showed that it's as effective as injections of ten times the amount of hypocretin.
The significance: a clean, low/no risk form of treatment that uses only 10% of the amount previously believed necessary.

2008 Hypocretin Nasal Spray's Effects on Olfactory Senses (Taste/Smell) using Humans (Dr. Baier):

Used the treatment on humans and demonstrated an improvement in taste/smell.
The significance: the is the first study using humans, and it had the effect the researches expected.

2011 Illness Related Lethargy Due to Low Hypocretin (aka Why Sick People Feel Bad) using Mice (Dr. Marks):

Showed that the reason people feel bad when their sick is because the body lowers it's hypocretin levels.
The significance: demonstrates the benefit of the treatment for chronically ill patients and gives reason to believe we could find common cause with other groups.

2011 Hypocretin's Role on Working in Light vs Dark using Mice (Dr. Siegal):

Showed that low/no hypocretin causes people to ignore reward-based work in light, but not in darkness. Penalty avoidance seems unchanged.
The significance: helps establish the validity of another confusing symptom of narcolepsy, namely the tendency to feel more awake in the dark and the limited effectiveness of using light to help wake up.

2011 Hypocretin Nasal Spray's Effect on REM Sleep using Humans (Dr. Baier):

Showed that hypocretin improves REM sleep during the second half of the night. The first half of the night was still disturbed, but could have been due to the timing of the treatment.
The significance: shows that the treatment has potential in improving both waking and sleeping symptoms, especially in REM sleep.

The Good News

All the doctors believe hypocretin replacement therapy shows a lot of promise in becoming an effective treatment. Doctors Siegal and Baier were specific in their belief that the nasal spray seems very promising.

The Bad News

Neither Dr. Siegal nor Dr. Baier seemed very optimistic that a pharmaceutical company would bring the hypocretin nasal spray to market in the near future. The reasons (listed below) were all primarily economic. I've elaborated on them, but each point was mentioned by one or both doctors. I'd like to point out that both doctors have been great allies through their research and seemed very disappointed about the lack of commercial interest.

  • Target Market is Too Small: To a pharmaceutical company, there aren't a lot of us to serve as prospective customers for treatment.
  • Hypocretin is Unpatentable: The molecule can't be patented and the delivery system wasn't developed in a way that it could be patented without special exception by the FDA. This means that any group with the necessary certifications could potentially make it.
  • Hypocretin Antagonists Seem More Profitable: While hypocretin itself isn't patentable, a synthetic that prevents it from doing its job is patentable. Several pharmaceuticals are developing antagonists to help insomniacs go to sleep. I wonder if they're aware of Dr. Baier's study on how the presence of hypocretin helps stabilize REM sleep.
  • It's Expensive: Getting regulatory approvals is generally a very expensive process that requires multiple human studies, trials, etc.



#9 severianthegreat

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Posted 01 November 2011 - 12:34 AM

All,
I thought it would be easier if I split the findings from thoughts on what might help make treatment a reality. See my previous post for what we've found so far. If anyone has anything to add or is able to find evidence that the treatment is being developed commercially, please post!

Suggestions: What Can Be Done Now?
  • Learn the process by which such a treatment can be developed, trialed, approved (by FDA), and brought to market, including what the total costs could be.
  • Contact the PR departments of pharmaceutical companies and inquire directly about if they are developing the treatment or on how to get them interested in developing the treatment.
  • Contact the Not-For-Profit Pharmaceutical Companies like OneWorld Health, Chemists Without Borders, Drugs for Neglected Diseases, etc. Some of these may focus on diseases in poor countries. But thankfully, the treatment has the potential for broad applications in improving symptoms of other diseases.
  • Contact the communities for other diseases, like cancer, Parkinson's, etc. to hopefully get them interested in working together.
  • If anyone has anything, please post!
Also, if anyone has any questions, experience in the industry, or contacts, please post or feel free to message me directly.

Thank you all for reading and sharing,
Eric

#10 Rrrapture

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Posted 27 November 2011 - 10:42 AM

Great research and synopsis, everyone! I feel hopeful after reading this thread.



All,
I thought it would be easier if I split the findings from thoughts on what might help make treatment a reality. See my previous post for what we've found so far. If anyone has anything to add or is able to find evidence that the treatment is being developed commercially, please post!

Suggestions: What Can Be Done Now?



#11 Emo

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Posted 27 November 2011 - 10:04 PM

Just encountered this topic. Severianthegrate, reporting about the lack of plans to develop a nasal hypocretin application, mostly due to economics, included:

"Hypocretin Antagonists Seem More Profitable: While hypocretin itself isn't patentable, a synthetic that prevents it from doing its job is patentable. Several pharmaceuticals are developing antagonists to help insomniacs go to sleep."

I remember when I first read about this plan which seems to be a plan to induce temporary narcolepsy in order to help insomniacs. I was thinking (and still do) that the plan is doomed. Just think of the warnings they'd have to announce during the TV commercials:

"Occasional bouts of hallucinations leading to reports of burglary, attempted arson, alien abductions, or the more rare cases of monsters eating Cincinnati."
"You may experience sudden full body collapses due to certain emotions, especially during rare moments of enjoyment."
"You may experience multiple awakenings or disrupted sleep all night long"
"Excessive daytime sleepiness may prohibit operating machinery while taking this medication"

Doomed I tell ya! You may be unhappy to find research and development of narcoleptic medications is not being done because of monetary reasons but on the other hand lots of totally stupid ideas are being pursued because of (they think potential) monetary reasons.

Emo
Expert On Everything And Too Lazy To Prove It

#12 Megssosleepy

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Posted 23 January 2013 - 03:13 PM

Well its been a little over a year since this thread was up and running... and still no new hope!  I really want that nasal spray!! 

 

They complain of cost?  Would it cost more then Xyrem I wonder...



#13 Andrew

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Posted 25 January 2013 - 12:23 PM

Well, somebody wanna call these guys to see if they're legit or spend $100 and try it?  Orexin-A sublingual drops.

 

http://orexindiet.com/



#14 Andrew

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Posted 25 January 2013 - 12:26 PM

Oh - also - it's $1000 bucks for 3mg.  The $99 bottle is .03 ng.  LOL.



#15 Andrew

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Posted 25 January 2013 - 12:40 PM

They also have another website with this:

 

Orexinal - natural orexin activator to improve wakefulness

 

Ooh - they have a 0.2 mL "Try before you buy" size.  It's a proprietary blend "Orexin Activating Matrix" LOL.  Nasal spray, not sublingual like the other one.  And can't find anything about this company, SF-based "Fischer Labs", anywhere on the Internet.

 

Just went through checkout for the 0.2 mL "Free" bottle.  $19.76 shipping.  From San Francisco.  I live in Northern California.  Canceled that transaction!  I also called them, went straight to voicemail.  Left a message.  We'll see.

 

Here's what they say about it:

 

 

 

 

What is OREXINAL® 

OREXINAL® is a safe and specially formulated all-natural aid that helps your body increase its natural production of orexin. OREXINAL®can be used to improve wakefulness in adults who experience excessive sleepiness due to one of the following diagnosed sleep disorders: narcolepsy, obstructive sleep apnea (OSA) or shift work disorder (SWD).

The Science behind OREXINAL® 

Scientists at the University of Cambridge studied how physiological mixtures of nutrients influenced orexin neurons, which are known to be critical regulators of wakefulness and energy balance in the body. Previous research had demonstrated that orexin neurons are inhibited by glucose. Surprisingly, the current study revealed that physiologically relevant mixtures of amino acids, the nutrients derived from proteins (such as egg white), stimulated and activated the orexin neurons. The researchers went on to show that when orexin neurons were simultaneously exposed to amino acids and sugars, the amino acids served to suppress the inhibitory influence of glucose.

"Electrical impulses emitted by orexin cells stimulate wakefulness and tell the body to burn calories. We wondered whether dietary nutrients alter those impulses." said lead researcher Dr Denis Burdakov of the Department of Pharmacology and Institute of Metabolic Science.

To explore this, the scientists highlighted the orexin cells (which are scarce and difficult to find) with genetically targeted fluorescence in mouse brains. They then introduced different nutrients, such as amino acid mixtures similar to egg whites, while tracking orexin cell impulses.

They discovered that amino acids stimulate orexin cells. Previous work by the group found that glucose blocks orexin cells (which was cited as a reason for after-meal sleepiness), and so the researchers also looked at interactions between sugar and protein. They found that amino acids stop glucose from blocking orexin cells (in other words, protein negated the effects of sugar on the cells).

Taken together, these results support a new and more complex nutrient-specific model for dietary regulation of orexin neurons. "We found that activity in the orexin system is regulated by macronutrient balance rather than simply by the caloric content of the diet, suggesting that the brain contains not only energy-sensing cells, but also cells that can measure dietary balance," concludes Dr Burdakov. "Our data support the idea that the orexin neurons are under a 'push-pull' control by sugars and proteins. Interestingly, although behavioral effects are beyond the scope of our study, this cellular model is consistent with reports that when compared with sugar-rich meals, protein-rich meals are more effective at promoting wakefulness and arousal."



#16 Andrew

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Posted 25 January 2013 - 12:55 PM

And one more reply, sorry for talking to myself, folks - I emailed Dr. Denis Burdakov at Cambridge and told him about that site and asked if he had anything to do with it. 



#17 Andrew

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Posted 25 January 2013 - 02:24 PM

Dr. Burdakov replied.  Here is his response verbatim:

 

 

Thank you, I indeed have nothing to do with it!

 

Denis
 



#18 DeathRabbit

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Posted 25 January 2013 - 05:58 PM

Hmm, so snake oil then? I mean I'm pretty desperate but I'm not about to shoot random *BEEP* up my nose unless I can verify the source, lol.



#19 Andrew

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Posted 25 January 2013 - 06:08 PM

Seems like it.  I left them a voicemail.  No callback.  I'll post here if they do.  I will ask good questions :-)



#20 AustinBoston

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Posted 13 April 2013 - 02:47 AM

Can't we just make it ourselves?