New Drugs Targeting CGRP Offer Hope: American Academy of Neurology

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Role Of CGRP and Antagonists In Migraine Attack (1)

CGRP is critically implicated in the occurrence and unfolding or progress of a migraine attack. CGRP or Calcitonin gene-related peptide is a powerful protein/peptide containing a short chain of amino acid monomers. It plays a critical role in transmitting pain signals through the body in events such as migraines. It is also involved in the vasodilation, inflammation, immune-modulatory responses among others during migraine attack apart from increasing heart beat and altering sensory transmission.

CGRP is produced by the peripheral and central neurons of our central nervous system specifically around the spinal cord and the trigeminal ganglion. Prior to and during migraine episodes, the central and peripheral neurons release more CGRP. This is then mediated through CGRP receptors (CALCRL and RAMP1) found throughout the body. One way to prevent pain from occurring is to block the receptors that receive the CGRP protein using a chemical/drug. Such drugs are called CGRP antagonists or CGRP blockers.

In a post of March 28th, 2012 I had written (‘CGRP Blockers & SRAs – The New Faces In Research For Migraine Management’) on work being done on drugs that targeted CGRP receptors but were abandoned after Phase III trials due to adverse reaction found in some of the trial population. (2).

Currently, two studies showing work with calcitonin receptor blockers have moved into Phase II trials. This means that though positive outcomes have been had from these researches involving smaller populations, larger studies are required to clear the drug for sale or prescription.

Research 1:

This involves a prospective drug that aims to prevent migraine from starting rather than trying to stop attack from progressing once it has begun. The drug involves monoclonal antibodies or antibodies that are identical immune cells – clones of their unique parent cell. Such monoclonal antibodies are being directed at the CGRP to target the protein.

This research examined 163 migraineurs for a period of six months, who had migraine attacks ranging anything from 5 -14 days every month. In this time, they gave the population either a placebo or the drug under study called ALD403 without the migraineurs knowing what they were taking. Those who took the drug reported a 66% reduction in number of migraine days and in 12 weeks time reported to be migraine-free.

As per lead author Peter Goadsby, MD, PhD, of the UC San Francisco and a member of the American Academy of Neurology, “These results may potentially represent a new era in preventive therapy for migraine. Migraine remains poorly treated, and there are few effective and well tolerated treatments approved that prevent attacks from occurring.” (3)

Research 2:

This potential drug in injectable form too is a preventative rather than a mitigator of migraine condition and is based on monoclonal antibodies targeting CGRPs. In Phase II trials as well, the research studied 217 migraineurs who experienced anything from 4-17 days of migraine days every month.

The population being observed was also administered either a placebo or the drug under study called LY2951742 via the subcutaneous injection route, without being told which was which for a period of three months. Those who were receiving the real drug reported more than 4 days less of migraine days in a month. However, they also experienced more side-effects such as abdominal pain and upper respiratory tract infections.

As per Dr. David Dodick, MD, of Mayo Clinic Arizona in Phoenix and a member of the American Academy of Neurology, “We’re cautiously optimistic that a new era of mechanism-based migraine prevention is beginning. There is a huge treatment need for migraine — the third most common and seventh most disabling medical disorder in the world” (4)

SOURCES:

  1.  Image Credit: The Role of CGRP and its Antagonists in Migraine- Peripheral Actions of CGRP: Neurogenic Inflammation;  Flipper.diff.org; Web April 2014; http://bit.ly/PsCR7O
  2. CGRP Blockers & SRAs – The New Faces In Research For Migraine Management; Web April 2014; https://migrainingjenny.wordpress.com/2012/03/28/cgrp-blockers-sras-the-new-faces-in-research-for-migraine-management/
  3. New drugs offer hope for migraine prevention; ScienceDaily News; Web April 2014; http://www.sciencedaily.com/releases/2014/04/140422162048.htm
  4. Stopping Migraines Before They Start; DailyRx.com; Web April 2014; http://www.dailyrx.com/migraine-patients-had-fewer-attacks-monoclonal-antibody-treatment

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Newly FDA-Approved Topamax For Migraines Raises Concerns Over Serious Side-Effects

Topamax

Recently-approved Topiramate For Adolescents Needs A Look Into Serious Side-Effects (1)

The Food and Drug Administration of USA recently (end of March 2014) approved the use of chemical topiramate in the 12 – 17 years of age group to prevent migraines. Topiramate is manufactured by drug corporation Janssen and sold under the name of Topamax. Such adolescents who report to a minimum of migraine episodes every month and have been given a clinical diagnosis of migraines in the last 6 months qualify for receiving a prescription of Topamax from their doctors to be used as a prophylactic medication.

Topamax originally came into the market in 1996 to treat seizures experienced in epileptic patients and was later also extended to manage other conditions such as need to reduce weight in obese and overweight patients.

However, the initial euphoria of being able to avail of the benefits of this drug are now subsiding with concerns that have been put forward by analysts from consulting firm GlobalData, on the severe side-effects Topamax comes with and those that have long been known to occur in adult patients. They are likely to be experienced by the adolescent migraining population as well and require a serious risk-benefit analysis before receiving a prescription.

Topamax is known to cause side-effects such as tiredness, dizziness, coordination problems, speech problems, changes in vision and sensory distortion.(2) In some cases it may cause sudden loss inn vision, memory problems, problems remembering words, brain fog, decline in cognitive condition and behavioral changes and the like.

As per GolbalData analyst Alvina To, “Migraine is experienced by both children and adults alike. For children in particular, these symptoms can affect school performance, social interactions and family life. The good news is that Topamax proved safe and well-tolerated in this patient group. But as with all anti-epileptic drugs, Topamax may also increase the risk of suicidal thoughts and behaviors in patients, as well as boosting the chances of cleft lip and/or cleft palate development in infants born to women who take the drug during pregnancy. It is therefore essential that all associated risks and benefits of Topamax are carefully assessed.” (3)

Randomized and placebo-controlled tests on Topiramate as well as trials on safety for this young age group was conducted on 103 patients who were diagnosed with migraines. In 72% of these patients, migraines were significantly reduced compared to 44% who took placebos.

Thus instructions have been given to neurologists to dispense a Medication Guide that spells out the safety and what to expect from the drug at time of giving a prescription. According to Eric Bastings, M.D., deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, “Adding dosing and safety information for the adolescent age group to the drug’s prescribing information will help to inform health care professionals and patients in making treatment choices.” (4)

Topamax tablets are available in potencies of 25 mg, 100mg and 200 mg.

SOURCES:

  1. Image Credits: Topamax; Pharma Agora; Web April 2014; http://www.pharma-agora.com/product/detail/1524-topamax-sprinkle-25mg; http://www.pharma-agora.com/product/detail/1524-topamax-sprinkle-25mg
  2. Topamax Side Effects Center; Rx List; Web April 2014; http://www.rxlist.com/topamax-side-effects-drug-center.htm
  3. Topamax safety concerns as a treatment for migraines in adolescents, despite recent FDA approval; The Pharma Letter; Web April 2014; http://www.thepharmaletter.com/article/topamax-safety-concerns-as-a-treatment-for-migraines-in-adolescents-despite-recent-fda-approval
  4. FDA approves Topamax for migraine prevention in adolescents; FDA News Release; Web April 2014; http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391026.htm

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