Migraine Preventive Therapy What ’ s in the Pipeline ?
by a single clone of cells or cell line and consist of identical antibody molecules . CGRP antibodies are currently the most exciting potential preventive agents being studied . Four CGRPs are now being studied in Phase III clinical trials . Each of these appear to be working well in terms of efficacy and tolerability based on the Phase II data and early Phase III studies . CGRP is an extremely important player in the migraine process . It is involved in vasodilation ( widening of blood vessels ), inflammation , and pain transmission .
Serotonin is another neurotransmitter . The triptans work acutely by stimulating serotonin ( 5- HT1 B , D , and F ) receptors . By stimulating the D receptor , the triptans inhibit the release of CGRP . It is felt that this action reduces not only vasodilation , but also inflammation and pain transmission . The effect of this action is short-lived , so the triptans are used almost exclusively for acute migraine abortive therapy . It is also believed that onabotulinumtoxinA may be working , at least in part , in the preventive therapy of chronic migraine by the prolonged inhibition of CGRP release for about 12 weeks .
Biologic agents , such as CGRP monoclonal antibodies , are manufactured in the laboratory starting with antibodies made in non-human species ( such as mice or rats ). Individual components of these non-human immunoglobulins are then gradually substituted , making them humanized ( 90 % human ) or even fully humanized ( 100 % human ). This substitution reduces the risks of immunological reactions against them that could either inactivate them or cause allergic reactions . These antibodies also have a long half-life , allowing them be administered monthly or possibly even at 3-month intervals . Currently , three of these potential therapeutic agents are being manufactured as a subcutaneous ( SC ) injection that will hopefully be easily self-administered by patients . The fourth CGRP is an intravenous ( IV ) preparation that will be administered by a nurse . Another group of potential therapeutic agents for migraine prevention are referred to as gepants . The gepants are small molecules ( in comparison to antibodies ) that block the CGRP receptor cells . The first of the gepants to progress through Phase III testing was telcagepant . Telcagepant showed efficacy as both an abortive agent for acute attacks and as a preventive agent . Unfortunately , telcagepant was associated with liver toxicity and never became commercially available . Other agents in this class are currently in clinical trials for both acute and preventive therapy . These newer gepants appear to have no evidence of liver toxicity which hopefully , will be maintained through clinical trials .
A combination drug currently undergoing clinical trials contains a mixture of dextromethorphan and quinidine . Its efficacy is attributed to its effect against glutamate , an excitatory neurotransmitter that is important in the migraine process . This agent also could work through modulation of sodium , potassium , and the calcium channels . At this point , however , it is too early to tell if this agent will be of major benefit . Substantial data suggest good tolerability , as the drug is already commercially available as a treatment for pseudobulbar affect . PseudoBulbar Affect ( PBA ) symptoms are frequent , uncontrollable outbursts of crying or laughing in people with certain neurologic conditions , such as stroke or brain injuries .
One investigational product being evaluated is a nasal spray of oxytocin . Oxytocin is a hormone released by the pituitary gland that causes increased contraction of the uterus during labor and stimulates the release of milk into the ducts of the breasts . Oxytocin receptors are often found in the company of CGRP receptors in the trigeminal system . Early studies suggest that this drug may someday be an effective preventive therapy . Other investigational products are also in early
18 HeadWise ® | Volume 6 , Issue 3 • 2017
170767 _ LOT A _ NHF Feb 2017 Vol . 6 Issue 3 . indd 18 2 / 15 / 17 12:48 AM