It was recently reported in a newspaper in London that a new drug was going to bring hope for millions of migraine sufferers. I had to quickly check on migraine and how this drug was going to help. Here is my account.

In the UK, it is estimated that there are 190,000 people who suffer an attack of migraine every day (Steiner et al, Cephalalgia, 2003) and women are more likely to have an attack than men. Children can be affected too. A WHO report indicates that migraine is one of the top 20 causes of disability expressed as years of healthy life lost to disability. Severe migraine attacks are classified by the World Health Organisation as among the most disabling illnesses, comparable to dementia, quadriplegia and active psychosis (Shapiro & Goadsby, Cephalalgia, September 2007)

A migraine is usually an intense headache that occurs at the front or on one side of the head. The pain is usually a severe throbbing sensation that gets worse when you move. Other symptoms associated with a migraine are nausea, this may be followed by vomiting, photophobia, phonophobia or osmophobia forcing many sufferers to rest in a quiet, dark room

It is estimated that a third of patients have an aura before the migraine. They include flashing lights, tingling sensation, disorientation and difficulty speaking. Very rarely they can also lose consciousness.

Not much is known about what starts an attack of migraine and what happens during the attack. This is one reason why no definite cure for the condition is available yet.

Present Treatment:

As there is no specific cure for migraine the treatment at the moment is mainly for the symptoms and avoiding anything that triggers symptoms.

Some of the drugs used in migraine are:
Antidepressants such as amitriptyline or venlafaxine, beta blockers or calcium channel blockers.
Anti seizure medications such as valproic acid, gabapentin and topiramate
Botulinum toxin type A (Botox) injections may also help reduce the attacks if they occur more than 15 days per month.

Other drugs generally used by patients when symptoms are mild include acetaminophen, ibuprofen, or aspirin. Triptans are prescribed to prevent an attack. Ergotamine and Isometheptene (Midrin) are also prescribed.

Before prescribing any drug it is most important to check if the patient suffers from any other medical condition like angina, hypertension etc as some of these drugs can cause a serious side effect on these patients.

Feverfew is a popular herb that has been tried for migraines. Several studies, but not all, support using feverfew for treating migraines.

Present Research:
We now know that Calcitonin Gene-Related peptide (CGRP) has a role in the process causing pain in migraine. During the last few years researchers have been finding a way to tackle CGRP to cure migraine.

What is CGRP.
CGRP is not easy to explain, but here are some basic facts:
It is an amino acid peptide produced by neurons and which has been implicated in the pathogenesis of migraine.The type of CGRP protein that researchers are currently looking at seems to have only one job – to cause pain. Triptans by increasing the amount of calcium inside cells, seems to decrease CGRP and OnabotulinumtoxinA (Botox) is believed to prevent release of CGRP.

CGRP is produced in both peripheral and central neurons. It is a potent peptide vasodilator and can function in the transmission of pain. In the spinal cord, the function and expression of CGRP may differ depending on the location of synthesis. CGRP is derived mainly from the cell bodies of motor neurons when synthesized in the ventral horn of the spinal cord and may contribute to the regeneration of nervous tissue after injury. Conversely, CGRP is derived from dorsal root ganglion when synthesized in the dorsal horn of the spinal cord and may be linked to the transmission of pain. In the trigeminal vascular system, the cell bodies on the trigeminal ganglion are the main source of CGRP. CGRP is thought to play a role in cardiovascular homeostasis and nociception.

Our brain does not feel pain. However, it is currently thought that during migraine, sensory neurons in the trigeminal ganglion are activated and release CGRP. The CGRP binds to special receptors that activate and cause many of the symptoms of migraine including vasodilation, inflammation and pain. Scientists have been trying to find a way to block these special receptors and prevent CGRP from binding to them. It was hoped that blocking CGRP from its receptors would help to control the debilitating pain of Migraine.

A drug called Telcagepant was found to block CGRP receptors. There was some success when it was taken during an attack. However when it went on trial it caused elevated levels of liver enzymes. It was therefore considered not safe and was withdrawn.

Today two new drugs are being presented at scientific meetings as possible wonder drugs to cure migraine. They are ALD403 from Alder Biopharmaceuticals, Inc. and Ly2951742 introduced by Eli Lilly and Company. ALD403 is a genetically engineered monoclonal antibody that targets CGRP for prevention of migraine. LY2951742 is a high affinity, neutralizing antibody to CGRP. Both these drugs have shown great promise in preventing an attack of migraine with no significant side effects. We must wait a few more months before we know for sure whether these drugs will be released for prescribing and whether they really are the answer for migraine sufferers.

For a research student: A little more about CGRP:

Calcitonin gene related peptide (CGRP) is a member of the calcitonin family of peptides, which in humans exists in two forms, ?-CGRP and ?-CGRP. ?-CGRP is a 37-amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11. The less-studied ?-CGRP differs in three amino acids (in humans) and is encoded in a separate gene in the same vicinity).

Receptors to which CGRP latches:
CGRP mediates its effects through a heteromeric receptor composed of a G protein-coupled receptor called calcitonin receptor-like receptor (CALCRL) and a receptor activity-modifying protein (RAMP1). CGRP receptors are found throughout the body, suggesting that the protein may modulate a variety of physiological functions in all major systems (e.g., respiratory, endocrine, gastrointestinal, immune, and cardiovascular).