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