Our findings support the efficacy and tolerability of monthly erenumab 140 mg as a preventive treatment in patients suffering from both migraines without aura and CH. We speculate that erenumab could represent a low‐risk alternative for CH patients (with or without comorbid migraine) who did not tolerate common CH preventatives therapies or for whom the therapies were not successful. Certainly, randomized trials are needed to confirm these observations and we hope that our data, showing a delayed therapeutic effect only with the highest dose of erenumab (140 mg/month), can be taken into account in designing future trials.

40 yrs CH, this one didn't work.
I could see how it would benefit in migraine, but in CH, it knocked maybe a whisper off a scream.
Good luck with it.

There are three facts, CHers and migraineurs need to understand about trying to prevent CH or migraines with monoclonal antibodies (mAbs) developed to neutralize Calcitonin Gene-Related Peptide (CGRP) - basically why they don't and won't work to prevent CH or MH.

1.  It's been well established in several studies, at least two by none other than the good Dr. Peter Goadsby, that CGRP is expressed (synthesized) primarily from within neurons of the trigeminal ganglia.  In order for any anti-CGRP intervention to down-regulate/suppress CGRP, it must enter these neurons.

2.  Size Matters.  Monoclonal Antibodies have a molecular mass of 150,000 Daltons (150 KDa).  The fenestration (windows) through the blood brain barrier (BBB) a.k.a., the arterial capillaries and microvasculature in the brain and in particular, within the trigeminovascular complex) have a maximum window size that allows molecules no larger than 400 Da to pass from the bloodstream through the BBB into brain tissues and neurons.  As the monoclonal antibodies (mAbs) have a molecular mass of 150,000 Da, they are 375 times too big to pass through the BBB.  If these mAbs can't get to the site of action where CGRP is expresses/synthesized, there's no way it can stop this process or completely prevent CH or migraine.

What appears to be happening is these anti-CGRP mAbs are lowering serum CGRP concentrations and this is possibly why there are slight reductions in migraine days as small amounts of CGRP is also expressed elsewhere in the body outside the CNS that's protected by the BBB.

3.  As usual, Big Pharma is so interested in profit it focused only on CGRP.  It turns out there are three other neuropeptides responsible for the neurogenic inflammation and pain we know as CH or migraine.  They are Substance P (SP), Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP).  You can google these peptides if you don't believe me.

The anti-CGRP mAbs made by Big Pharma do NOTHING to suppress SP, VIP or PACAP so there's no way they can completely prevent CH or migraine headaches.

On the other hand, vitamin D3 has a molecular mass of 385 Da and 25-Hydroxy Vitamin D3, a.k.a. 25(OH)D3 has a molecular mass of 400 Da.   Accordingly, both vitamin D3 and 25(OH)D3 pass through the BBB and enter neurons in the trigeminovascular complex where they are hydroxylated to 1,25(OH)2D3, the genetically active vitamin D3 metabolite that down-regulates the expression (synthesis) of CGRP, SP and VIP.  They also enter neurons within the pituitary gland to down-regulate the expression of PACAP.

So much for today's lesson in molecular biology as it applies to cluster and migraine headache.

Take care,

V/R, Batch

I've been reading of lots of folks having success with this.

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Cheers Hoppy

Hello Batch. I have been reading this post back and forth over the last couple of days, I am firstly wanting to tip my hat off to you for your contributions - you’re explanations are fantastic.
I’m wondering if you are following any developments in the research and clinical trials of both CGRP (eptinezumab) and PACAP (ALD1910) monoclonal antibody medicines and if there is a good place to keep an eye on developments in this area?
It sounds promising - albeit I think I’ll stick with the down regulation properties of vitamin D3 for now, certainly things look hopeful for the future; there seems to be a lot of research and interest in studying these neuro peptides and their relation to neurogenic headache disorders at the moment.
From following your posts and your sheer dedication in understanding the CGRP cascade, it appears to me this is the holy grail of understanding cluster headache, and again I thankyou for imparting your knowledge SIR - I know there are thousands of people grateful for it, myself included.

Alternately, you could read the following extract from genuine scientific research (emphasis added):

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Abstract

Introduction: Calcitonin Gene-Related Peptide (CGRP) plays a crucial role in migraine pathophysiology. A novel specific treatment strategy for the prevention of migraine incorporates monoclonal antibodies (mAbs) against CGRP and its canonical receptor. Eptinezumab, fremanezumab and galcanezumab block CGRP mediated effects by binding to the peptide, while erenumab blocks the CGRP receptor.Areas covered: Following a brief overview of pharmacological characteristics, we will review phase III trials for the use of CGRP mAbs in the prevention of episodic and chronic migraine.Expert opinion: All four CGRP mAbs demonstrated an excellent safety, tolerability and efficacy profile in migraine patients. Across all trials mAbs showed superior efficacy for the reduction of monthly migraine days compared to placebo with a net benefit of 2.8 days. Neither cardiovascular nor immunological safety concerns have emerged from clinical trials. Fremanezumab, galcanezumab, and erenumab are approved in the USA and Europe. Based on trial data there is no reason why these mAbs should not become first-line therapies in future. For now, we advocate for the use of mAbs in migraine prevention for patients who failed a minimum of two standard oral treatments based on the novelty and costs of this approach. mAbs are also effective in patients with medication overuse and with comorbid depression or anxiety disorders. Taken together, mAbs are likely to usher in a new era in migraine prevention and provide significant value to patients.