New CGRP Drug Tastes Success In Last Stage Clinical Trials, To Hit Markets Soon

Stressed Woman.jpg

New Drug Can Stop A Migraine From Occurring (1)

The role of CGRP or Calcitonin Gene-related Peptide has been implicated in migraine research since 3 decades now. However, the exact nuisances to trace the working of CGRP and then tame it’s effects during a migraine attack was being studied and at times led to hopes for migraineurs but further tests on those hypotheses on which some of the drugs worked, failed.

CGRP is basically a neurotransmitter that is produced by cells in our central nervous system (CNS) and also by peripheral neurons. As the name suggests, it is a peptide or a chain wherein several amino acid molecules are linked to each other. CGRP’s main function is to cause vasodilatation or swelling of cranial arteries and cranial membrane, and transmission of pain. (2)

When CGRP is released by the CNS neurons into our blood, it is affected by two types of receptors: Calcitonin receptor-like receptor (CALCRL) and, a receptor activity-modifying protein (RAMP1).

Over the years drugs have been made to block these receptors during a migraine episode with new drugs but they have been found to be too toxic for the human liver. Currently, a few pharmaceutical corporations such as Amgen/Novartis, Teva and Eli Lilly are in the brink of bringing revolutionary CGRP drugs that work for us without unleashing a series of serious side effects.

Based on the data obtained on its 2 successful phases of trials of their new drug (galcanezumab), Eli Lilly concluded that in episodic and chronic migraine, a 50% reduction was seen in around 60% of patients on galcanezumab versus 36%-39% of placebo users, with all migraine attacks eliminated in 12%-15% and 6%, respectively.

As per the Christi Shaw, President at Lilly Bio-Medicines, “the findings are a crucial step forward for the millions of patients living with migraine that have not yet tried, or found, an effective preventive therapy.” (3)

At the moment, Lilly is trying to differentiate galcanezumab with the drugs from the pharma companies who are in the run for licenses to sell, on the basis of its Phase III program in cluster headaches which is due to read out next year, and has said it hopes galcanezumab will be the first drug in its class with pivotal data in this indication.

As per Peter Goadsby, neurologist at King’s College London an UCSF is of the opinion that, “We’re in a genuine watershed moment with the very first class of migraine treatments that can prevent the attacks from actually happening. It’s incredibly encouraging and provides much needed hope to people who continue to struggle despite a range of currently available treatments.” (4) He noted this of all the CGRP-based therapies by the different pahrma companies that were possibly to hit the market.

In the meanwhile, Lilly has acquired CoLucid with it’s lead drug lasmiditan. Lasmiditan is to arrive in 2018 as an orally taken 5-HT 1F receptor agonist against acute migraine attacks. Data reported on this drug have been favourable and were reported at the AHS meeting. It was noted that significantly more participants were free of headache pain and other symptoms such as nausea, or aversion to loud sounds or light two hours after treatment with lasmiditan, compared to placebo.

SOURCES:

  1. Picture Credit: FreeDigitalPhotos; “Stressed Businesswoman” by Ambro; http://www.freedigitalphotos.net/images/agree-terms.php
  2. Calcitonin Gene-related Peptide; Wikipedia; https://en.wikipedia.org/wiki/Calcitonin_gene-related_peptide
  3. Lilly’s CGRP Inhibitor Galcanezumab Hits The Mark In Migraines As Race To Market Kicks Off; Fierce Biotech; Phil Taylor; June 2017; http://www.fiercebiotech.com/biotech/lilly-s-cgrp-inhibitor-galcanezumab-hits-mark-migraine-as-race-to-market-kicks-off
  4. AHS Meeting Release CGRP; 59th Annual Scientific Meeting; https://americanheadachesociety.org/ahs-meeting-release-cgrp/

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Green Light To Milder Migraine Pain

gREEN BEAM

There is hope yet for migraineurs. If science cannot do away with migraines altogether, the word is out that you can at least have lower intensity pain episodes than what you experience in your migraine episode.

Tests were conducted by Dr Rajesh Khanna. a professor of pharmacology at the University of Arizona and Dr. Mohab Ibrahim, director of the Chronic Pain Clinic and Chronic Pain Fellowship at Banner-University Medical Center.

The tests were initially run on rats with significant results and then they were extended to pain patients who were subjected to 2 hours a day of green light for a period of 10 weeks. Some other pain patients were exposed to a similar period of white light.  The green light group said their pain from migraine and fibromyalgia dropped 40 to 50 percent.

As per Dr. Khanna, “At a chemical, a neurochemical level, it does something to tune the system, so essentially what it’s doing is increasing your happy hormones, your level of endogenous opioids.” (1)

Ibrahim and Khanna hope to get grants from the Department of Defense and the NIH so they can expand the study. They also caution people not to give up their pain medication. A detailed report along with the findings can be viewed here: http://ow.ly/qtKl30efr3k

Results of a similar study were published in Brain last year in May. A group of scientists at Harvard Medical School had conducted those tests.

In a migraine attack, the migraineurs experiences not just incapacitating pain, but also develop aversion to light and sound as well as array of other symptoms like nausea, visual and motor impairment. Aversion to light or photophobia during a migraine episode affects 80% of all migraineurs.

The study showed that a narrow band of green light at low intensity reduces the intensity of the pain being experienced. Burstein, Professor of Anesthesia at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, and lead author of the study, and his colleagues found, unexpectedly, that green light actually reduced their pain by about 20%. (2)

Bands of light in other colors and higher intensity lights including green actually pegged up the pain experience.

To be able to comprehend this phenomenon, the scientists devised experiments in which they measured the magnitude of the electrical signals generated by the retina (in the eye) and the cortex (in the brain) of these patients in response to each colour of light. They found that green light generated the smallest electrical signals in both the retina and cortex.

SOURCES:

1.     Health Beat: Green light for pain relief: Migraines; Melanie Falcon, August 7, 2017; http://www.wfmz.com/health/health-beat/health-beat-green-light-for-pain-relief-migraines/601026622
2.     Science Daily: A narrow band of green light could improve migraines; May 17, 2016; https://www.sciencedaily.com/releases/2016/05/160517083042.htm

JOURNAL REFERENCE:

Rodrigo Noseda, Carolyn A. Bernstein, Rony-Reuven Nir, Alice J. Lee, Anne B. Fulton, Suzanne M. Bertisch, Alexandra Hovaguimian, Dean M. Cestari, Rodrigo Saavedra-Walker, David Borsook, Bruce L. Doran, Catherine Buettner, Rami Burstein. Migraine photophobia originating in cone-driven retinal pathways. Brain, 2016 DOI: 10.1093/brain/aww119

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New Beginnings, New Year

HAPPY NEW YEAR 2016

As 2015 draws to a close, I hope for the readers that this year was blessed with happy memories and useful learnings. As 2016 stands at our threshold, I wish for each one of us, a very very Happy New Year. Hoping we all dive into 2016 full of enthusiasm and positivity. #2016

Image credit: Happy New Year 2016 Card. Colorful Snow In Winter On Blue Sky Background By Tanya3597 on freedigitalphotos.net

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New Research From AAN: Your Pain Threshold Directly Links To Cortical Thickness

Brain Cortical Thickess

Brain Cortical Thickness Directly Implicated In Feeling Migraine Pain (1)

A new study presented by Mayo Clinic at the AAN’s (American Academy of Neurology) 67th Annual Meeting was highlighted by the Vice Chair of the Academy. The study clearly demonstrated that there was a direct and positive correlation between the cortical thickness in the brain and the thresholds of pain in migraineurs.

As per the Vice Chair of the AAN, Dr. Rost, who is also the director of acute stroke services at the Massachusetts General Hospital and an associate professor at the Harvard Medical School, “The object of study was to evaluate the cortical thickness in the areas that are potentially associated with pain processing.” (2)

Incidentally, other independent studies conducted previously have also indicated that migraineurs are hypersensitive to perceiving their pain partially because they are over-vigilant to certain painful stimuli and are usually not able to distract themselves from the pain or pain stimuli successfully.

The study examined a total of 63 subjects out of which 31 were migraineurs and the remaining were healthy individuals and formed the control group. Using the T1 sequencing technique in MRIs they studied the cortical thickness of each region of their brains and calculated the relation to the person’s pain threshold.

The values arrived at showed a negative correlation in cortical thickness and pain threshold among non-migraineurs. However, the control group had lower cortical thickness in the area of their interest. On the contrary, migraineurs not only had a positive correlation but had less tolerance to specific pain stimuli. The most significant difference in the cortical thickness between the migraineurs and the control group was found to be in the left superior temporal, anterior parietal regions of the brain. Thus this finding, along with some previous studies form a new approach where the doctors should not only use the old techniques to manage migraines but also apply new one where migraineurs are able to inhibit their pain to a significant extent by distracting themselves from it.

According to Dr. Rost, “This is in face the region of the brain that participates in attention to painful stimulus and orientation to that stimulus. It opens an interesting segue into the dynamic interaction of neurons during a migraine. There is a way to retrain the brain and that plasticity, biofeedback and other therapies, play a role in that.”

SOURCE

  1. Human Brain by Dream Designs via Stock Photo; Freedigitalphotos.net; Web May 2015; http://www.freedigitalphotos.net/images/human-brain-photo-p214120
  2. A New Way To Think About Migraines: Biosciencetechnlogy.com; Web May 2015; http://www.biosciencetechnology.com/articles/2015/05/new-way-think-about-migraines
  3. Correlations between Brain Cortical Thickness and Cutaneous Pain Thresholds Are Atypical in Adults with Migraine; PLOSOne.com; Web May 2015; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099791

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Migraineurs’ Likelihood Of Getting Stroke Graded

Migraine Blog Stroke

Migraineurs with Aura Double the Risk of Stroke…and more… (1)

A study conducted by the senior neurologists at the Loyola University Medical Center has put forth its findings that:

  • People who experience migraines with auras are at roughly double the risk of ischemic strokes.
  • The study also arrived at the shocking conclusion that such migraineurs as those who smoke were thrice as likely to have stroke in their lives.
  • Migraineurs who smoked and used birth control pills were 7 times more likely to suffer strokes.
  • Migraines also pegged a person’s risk of heart attacks and arterial claudication – a condition that causes poor circulation of blood in the legs and limb extremes causing pain.

The conclusion was put out after the results several independent studies were analysed. This meta-analysis has brought out the direct link between migraines and stroke risk. This and similar other studies have been discussed by lead neurologists Dr. Michael Star and Jose Biller M.D at the Loyola Medical Center in the chapter Headache and Migraine Biology and Management.

As per Drs. Star and Biller, “Taking all of these possible explanations into account, the research may point to stroke and migraine sharing a reciprocal causal relationship.” (2) Ischemic strokes or brain attacks cause brain cell death by the limiting or totally stopping the supply of blood to certain brain tissues. Most often an ischemic stroke can be caused by thrombosis or the obstruction of blood vessel by a blood clot forming locally. Almost 85% of all strokes are of ischemic nature (thus making them the most common types of stroke). Some evidence also exists showing a link between migraines and hemorrhagic strokes. Hemorrhagic strokes are caused by rupture of blood vessels of the brain and are considered the more deadly of stroke types.

So far the biology that exists and underlies the relationship between migraines with aura and strokes has been sketchy and poorly defined at best. According to the neurologists, “There is a significant amount of research attempting to further elucidate this multifaceted relationship.” (3)

Through these studies the researchers have proposed several explanations that could explain the linkage between migraines with aura and stroke occurrence:

  1.  Increased risk of cardiovascular diseases in migraineurs
  2. Low levels of HDL or good cholesterol in migraineurs
  3. High levels of c-reactive protein
  4. Presence of specific genes that predispose them to migraines and strokes
  5. Consumption of certain medications that pegs the migraineurs risk of stroke
  6. A phase-phenomenon that occurs in migraine attacks called cortical spreading depression during which strokes occur. During this phase there occurs a slowly propagated wave of depolarization, followed by depression of brain activity setting into motion changes in neural and vascular function.

SOURCES

1.     Woman Having Headache At Home; Stock Photos; Image by Marin; Web April 2015; http://www.freedigitalphotos.net/images/woman-having-headache-at-home-photo-p173634

2.     People who suffer migraine headaches may be at double the risk of stroke; Science Daily News; Web April 2015; http://www.sciencedaily.com/releases/2015/03/150324111326.htm

3.     People who suffer migraine headaches may be at double the risk of stroke; Loyola Medicine – Newswire; Web April 2015; http://www.loyolamedicine.org/newswire/news/people-who-suffer-migraine-headaches-may-be-double-risk-stroke

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What Should Work, What Might: Migraine Meds Reassessed

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New Studies Re-assesses Migraine Drug Efficacies (1)

Efficacy of migraine drugs was under another new review from researchers who have examined all of the scientific literature available on the treatment as well as followed up on migraine patients and the scientists have come up with what in their view prove effective in acute cases of migraine. Besides these 2 criteria the study was also based on the depth of the published research done on the medications as well as the quantum of studies on them.

The conclusions of the new study at a glance are:

DEEMED EFFECTIVE (LEVEL A) PROBABLY EFFECTIVE (LEVEL B)
TRIPTANS – Sumatriptan, Zolmitriptan, Rizatriptan, Frovatriptan, Almotriptan, Naratriptan, Eletriptan, Avitriptan OPIOID – Codeine+Acetaminophen, Tramadaol+Acetaminophen
Dihydroergotamins
NSAID – Aspirin, Ibuprofen, Naproxen
OPIOID – Butorphanol Nasal Spray
Caffeine with NSAIDS

Findings of the study were published in the January 2015 issue of the medical journal Headache. As per Dr. Stephen Silberstein , professor of neurology and director of the Jefferson Headache Center of Thomas Jefferson University in Philadelphia, “We hope that this assessment of the efficacy of currently available migraine therapies helps patients and their physicians utilize treatments that are the most appropriate for them.” (2)

Based on the study criteria, drugs were thus rated as deemed effective (Level A), probably effective (Level B), possibly effective (Level C). For such medications where the proof was found either inadequate or gave such results which refutes the use of that medicine, was classified as Level U. For a drug to be classified as deemed effective or a Level A drug, the studies done on the drug must be supported by at least well-designed, double-blind, randomized, placebo-controlled clinical trials.  (3)

The American Headache Society will soon be translating the research findings that will aid in providing evidence-based guidelines to clinical practice. In any case, doctors treating migraine patients must consider the individuals on a case to case basis keeping in view the drug side-effects, patient history, costs and drug efficacy.

SOURCES

  1. Image credit: Pills and Capsules – Stock Photo; freedigitalphotos.net; Web February 2015; http://www.freedigitalphotos.net/images/pills-and-capsules-photo-p308698
  2. Study Rates Migraine Medications; WebMD.com; Web February 2015; http://www.webmd.com/migraines-headaches/news/20150120/study-rates-migraine-medications
  3. American Headache Society Provides Updated Assessment of Medications to Treat Acute Migraine; Newswise.com; Web February 2015; http://www.newswise.com/articles/american-headache-society-provides-updated-assessment-of-medications-to-treat-acute-migraine

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