Glutamate: A New Key To Migraine Treatment?
Information presented at the 61st Annual Meeting of the American Academy of Neurology (April, 2009) indicates that glutamate receptors may play a role in Migraine treatment.
Trial Phase IIa data showed Addex Pharmaceuticals' ADX10059, an investigational glutamate receptor inhibitor, could prove helpful for Migraine prevention. Other early trials have shown ADX1005 to be an effective abortive treatment for acute migraine attacks.
Glutamate is a neurotransmitter, a chemical occurring naturally in the brain that transmits messages from one nerve cell to another.
A theory under investigation is that since glutamate receptors are found in regions of the brain involved in Migraine, inhibiting transmission through glutamate receptors could lead to Migraine treatments.
Dr. Peter Goadsby of the UCSF Headache Center and investigator in the study commented:
"Medication is available to prevent migraine but these treatments are often secondary uses of the drug and come with potentially limiting side-effects... New therapies specifically developed for migraine prevention are urgently needed especially for the substantial proportion of migraine sufferers who have frequent attacks and have significant disability in their daily lives. Targeting mGluR5 (glutamate) signaling with ADX10059 is an interesting approach that is showing significant promise in early clinical evaluation."2
"It wasn't a great effect, but it confirms that glutamate is a legitimate target... It's generally quite clear that there is glutamate-mediated transfer of pain signals in migraine... The question is how to take advantage of it."1
According to Goadsby, ADX10059 works by "toning down" the receptors as opposed to totally blocking them.
The trial showed:
- Pain-free response two hours after taking ADX10059 was significantly greater than placebo.
- Only 10% remained pain-free at 24 hours with ADX10059, compared with 3.1% for placebo, a difference that was not statistically significant.
- ADX10059 was not as well tolerated as placebo, causing central nervous system adverse events such as cognitive effects and fatigue more commonly than placebo (71% versus 14%).
Even in the face of these less than stellar results, Dr. Goadsby said he remained hopeful that these compounds have potential for the prevention of migraine, and he is involved in a trial of the compound for this effect, adding that using lower doses over longer periods of time for prevention might avoid the side effects observed in this trial.
Summary and comments:
At this time, there are no medications on the market that were developed specifically for Migraine prevention. All of the 100 plus medications in use are "hand-me-down" medications, medications that were originally developed for other purposes. The possible development of a new class of medications is exciting and hope inspiring.
Even though ADX10059 showed problems in this phase IIa trial, it's still early. Hopefully, it will prove to be a safe and effective preventive even if it doesn't work out as a Migraine abortive medication.
1 Fiore, Kristina. "AAN: Glutamate Receptor Inhibitors May Help Migraine." MedPage Today. April 30, 2009.
2 Press Release. "Data Suggests Glutamate Receptor "mGluR5" is Clinically Relevant for Migraine." Adex Pharmaceuticals. Geneva, Switzerland. April 29, 2009.
3 Goadsby PJ, et al "Investigation of the role of mGluR5 inhibition in migraine: A proof-of-concept study of ADX10059 in acute treatment of migraine." AAN 2009; Abstract P06.006.