Calcium Chanell Gene Recepptor Antgonists ---CGRP Antagonists

04 Jan, 2017 - 4:45 pm

Neurologists await the reports of CGRP Antagonists both for Migraine and Cluster Headache.

These are the latest LIGAND (receptor) thought to play an important role in Headache Pain Modulation.

Phase 3 trials are underway in both the US and Europe..

Hopefully this breakthrough will benefit suffers of Cluster Headache. It is an area worth watching for outcomes.

The pharmaceutical industry is pushing for better relief. This group of drugs has the potential to be a CURE.

CGRP is a monoclonal antibody directed at the pain receptor. Monoclonal antibodies are widely used in Medicine. The commonest current Neurology example is Natulizumab--used for MS. There are at least 3 in the process of release for MS.

The MAB at the end of the drug name indicating it is a monoclonal antibody..

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18 May, 2017 - 12:39 pm

I will be watching this with eager anticipation.

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26 Jun, 2017 - 12:17 pm

Good news, CGRP Antagonists are now at Phase 4,which is immediately before release by the FDA (USA).
P
My colleague Prof Peter Goadsby is involved with one.

There are 4 to be released; they require a monthly injection for about 6 months. I know nothing of costs at present.

An increased number of neurologists are doing the suboccipital injection (back of head) for cluster headache.

In 6 months of busy practice in Hervey Bay and Gympie--I have yet to see a case of Cluster (maybe they are clustered elsewhere)

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28 Jun, 2017 - 8:56 am

I would like to be able to forward this information on to my neurologist in Liverpool, is there somewhere I can collect more information?

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29 Jun, 2017 - 5:43 am

Hi,

Prof Peter Goadsby (Aussie) is based in King's College , London-but commutes to San Francisco.

Maybe a referral to Peter's Unit would be useful. All of my knowledge of CGRP antagonists is with Migraine--however ,it is applicable to Cluster.

I assume you use oxygen ,and know about subcutaneous sumotriptan 3-6 mg.??

Keep me informed

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29 Jun, 2017 - 7:29 am

I have not been prescribed oxygen. I use Indomethacin as a preventive during cluster periods and sumitriptan nasal spray (imigran) as an abortative.

Prof. Goadsby works out of London, am I reading that correctly? I am simply after the information so I can potentially inform my Neurologist if he is unaware of the developments being made in this field.

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05 Jul, 2017 - 9:20 am

Jacky,

Pardon me , but I assume you are female. Cluster is far more common in males. Females can get periodic hemicranias---responds ONLY to Indomethacin.

Hs this been considered in your diagnosis. Right, Peter works out of London.

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05 Jul, 2017 - 10:36 am

Nope, male. I believe I have had this discussion with you before.
27 y/o male with episodic clusters treated with indomethacin and sumitriptan.
However, my most recent bout of clusters the indomethacin treatment wasn't as effective as when first prescribed.
Also, I have noticed when having my neck tilted in a certain position for too long I.e, laying on a bed with arm supporting my head I can trigger a less painful cluster style headache.

How would a referral to Prof Goadsby's clinic be possible if he works in London, I am an Australian resident? Is it possible to get my Neurologist informed on the topic as well, is what I am asking.

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05 Jul, 2017 - 12:31 pm

Sorry,

I was answering another post from another section.

If the headaches are made worse by neck posture, firstly you need a neck MRI. If normal, then a suboccipital injection--most neurologists know the technique.

While Prof Goadsby is in London, we are long term friends. We both worked with Prof Michael Anthony at Prince of Wales Hosp Sydney--he was doing these injections in the 1980's.

Are you sure they are cluster headaches; hemicrania, SUNCT and SUNA need consideration by a Neurologist.

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05 Jul, 2017 - 12:35 pm

To be honest I am only going off what I have been diagnosed with from my Neurologist. I have to travel a significant distance and visits are expensive, but I shall endeavour to make another appointment to discuss this exchange with him.

Thanks for your insight, I appreciate it.

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05 Jul, 2017 - 2:02 pm

Have you asked your GP about Telehealth ,and the Telstra Health Anywhere Health program

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06 Jul, 2017 - 12:48 am

Hi JackyV,

i found your post from 5 july very interesting.
my first CH happened exactly as you described,
lying down (reading) with arm / hand supporting my head.
until now i had not heard of anyone else having the same experience.

the indomethacin puzzles me.
i tried it with no success.

i have read that indomethacin is used as a diagnostic tool
to rule out CH. that is if it stops the headache then it is not CH.

Indomethacin is spectacular in stopping paroxysmal hemi crania .

i am not saying you or your doctor are wrong, just suggesting
it might be worth further investigation to determine exactly
what sort of headache you have.
therefore leading to the most effective treatment for you.

regards kim

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06 Jul, 2017 - 11:17 am

Kim,

As a Neurologist of 35yrs,I agree with you completely. I have never heard of Indomethacin in CH.

However, it works in Hemicrania--I had my first case in 1979.

My greatest hope is that the CGRP Antagonists work for Cluster Headache

There are rare "mixed" headaches. I have one with some hemicranias and some cluster.Some of these cases are helped by Lithium.

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06 Jul, 2017 - 12:18 pm

My grandmother suffered from hemicrania. She was treated with lithium well into her older life.
My headaches definitely have traits of clusters, set off by alcohol during cluster periods, strike around the same time during bouts etc.
The neck posture triggering headache is only a recent development.

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10 Jul, 2017 - 8:18 am

Hi All,

The longer I am a Neurologist the more I learn, and realise what I don't know.

Who knows what sensible answers we will have to today's imponderables.

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09 Mar, 2018 - 10:04 am

The title of this thread should read - Calcitonin Gene-Related Peptide Antagonists.
Calcium Channel Antagonists (Diltiazem, Verpamil etc) are a different drug class.

Many of these CGRP receptor antagonists have fallen over during trials, mostly the -gepant class.
In Feb 2018, Ubrogepant seems to be working, in Migraine.
http://www.pharmatimes.com/news/trial_success_for_allergans_anti-cg
rp_migraine_drug_1220841

Thanks go to Goadsby & Edvinsson for finding the therapeutic target CGRP, but perhaps we're looking in the wrong place?
What is happening now, is the MAB, Mono-clonal Anti Body injection for Migraine.
There is some cross over in migraine trials for CH.
https://www.medscape.com/viewarticle/873510
From what I read, the MAB injection is likely to be really expensive, and probably not subsidised.
There is a long way to go in Australia with Sumatriptan not yet PBS subsidised for use in CH, so I doubt they'll go for an MAB at a cost of thousands of $$$ per shot.
Until that gets off the ground, in the mean time there's the D3 regimen for CH, it's cheap and it works.

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10 Mar, 2018 - 11:52 am

The above also is quite correct the verapamil falls into the category of a calcium channel blocker. The CGRP antagonist are quite different and they were both within the brain, and also at the trigeminal sensory ganglion.

Unfortunately cluster headache is referred to as a trigeminal autonomic cephalgia and The CGRP antagonist did not cross the blood brain barrier. However the so-called Gepant group Crosses barrier.

Several recent authors have raised different issues it is well known that lithium carbonate has been used to treat cluster headache for the last 50 years. However its side effect profile is quite high and its dose has to be carefully regulated it can affect kidney function and also thyroid function.

In the treatment of migraine––versus the treatment of cluster headache there are for current CGRP antagonist and contrary to the above author none of these of so-called fallen over there all almost ready to be released for the treatment of migraine.

Unfortunately in Australia the treatment of migraine still revolves around high flow oxygen, the use of verapamil. Ideally a subcutaneous or intramuscular injection of Imigran 6 mg would also be efficacious but it is not covered by the current pharmaceutical benefits came.

There is some work been done at the present time with restricted use of Botox injections into the area of scalp involved with cluster headache, I have tried it in a couple of cases however I am yet to be convinced that it has any benefit.

As I previously indicated the suboccipital injections had been used for over 50 years and a widely used in headache clinic throughout the world.

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10 Mar, 2018 - 4:24 pm

My last report was done with voice dictation; it is the treatment of cluster that is based on high flow oxygen

Verapamil is the commonest preventative medication and is over 40 yrs. old.

Lithium is used for Chronic cluster--less common than episodic cluster.

Indomethacin is used for hemicranias.

Having said all the above; there are cases that can have some cluster features and some migraine

There are 4 CGRP drugs completed phase 3 approval with the US FDA and awaiting approval; there is one Gepant.

There are now Australian Neurologist members of the Australian headache society. Just as some neurologist specialising in epilepsy ,MS or Parkinsons--there are probably 25 specialising in Headache..

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10 Mar, 2018 - 4:36 pm

One point I did not mention is that all Cluster Headache patients should have a high Quality (3 Tesla) MRI of the Brain and Pituitary Gland.

There is an association between cluster headaches and pituitary microadenoma's (small growths)

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17 Mar, 2018 - 6:46 pm

Wanna check that title again chief?

From the paper: "Calcitonin Gene-Related Peptide (CGRP) - A New Target for Migraine"

"Unfortunately, further development of telcagepant was discontinued in 2011 following the discovery that it led to elevated liver transaminases, an indicator of liver toxicity, in two patients (72a). This occurred in a Phase II trial designed to test the drug for twice-daily use over three months as a prophylactic "

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392770/

Clinical Trials.Gov Telecagepant status: "Terminated (The study was terminated based on a recommendation of the DSMB following the identification of two patients with significant elevations in serum transaminases) "

Reference: https://clinicaltrials.gov/ct2/show/NCT00797667?term=telcagepant&ra
nk=5

CGRP - Calcitonin Gene related Peptide, is as it says, a peptide.
CGRP antagonists are a drug class.
A Calcium Channel Blocker is just that, Verapamil, Dialtiazem, etc.
Completely unrelated drug classes.

Hmm...

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