Migraine Relief From Tinted Specs

Precision tinted lenses have been used widely to reduce visual perceptual distortions in poor readers, and are increasingly used for migraine sufferers, but until now the science behind these effects has been unclear. Now research published in the journal Cephalalgia, published by SAGE, uses functional magnetic resonance imaging (fMRI) for the first time to suggest a neurological basis for these visual remedies.

The new research shows how coloured glasses tuned to each migraine sufferer work by normalizing activity in the brain. The researchers saw specific abnormal brain activity (known as hyperactivation) when migraine sufferers saw intense patterns. The tinted lenses considerably reduced the effect.

Jie Huang along with colleagues from Michigan State University and the University of Michigan, US, and the University of Essex, UK, homed in on specific visual stimuli known to trigger migraines. These patterns, high contrast stripes or 'gratings,' can give the illusion of shape, colour and movement. These not only trigger migraines but also may cause seizures in those with photosensitive epilepsy.

Before the brain imaging took place, participants were tested and prescribed precision ophthalmic tints (POTs) with an Intuitive Colorimeter. Previous studies have suggested that some 42% of migraine with aura sufferers saw their migraine frequency halved on days when they wore POTs. The researchers used the colorimeter to illuminate text with coloured light, manipulating hue and saturation at constant luminance. For each test participant this gave an optimal hue and saturation (chromaticity) of light that led to the greatest comfort, reducing perceptual distortion. The test subjects then viewed stressful striped patterns illuminated with their optimal coloured light settings to screen for efficacy. The researchers used these readings to generate both effective POTs for each migraine sufferer and also two other pairs of grey and coloured lenses with slightly different properties as controls. 11 patients who frequently suffered from migraine enrolled in the fMRI study. Each patient was paired with a migraine-free control, who was also tested with that patient's three sets of lenses.

Once in the fMRI machine, the researchers exposed subjects to a range of striped patterns - these had varying likelihood of triggering distortion and discomfort. This study aimed to investigate the effect of the POTs on the cortical activation induced by the stressful pattern in each of the visual areas of the brain. Although patients reported some relief using all of the lenses (by around 40%), the POT lenses had a significant effect when viewing the stressful stripes (70% discomfort reduction). Both control and migraine patients responded similarly to the non-stressful stripe patterns, and in these cases all three lenses made no difference to the result. The POTs specifically suppressed cortical activation for migraine sufferers in visual area V2 of the occipital cortex of the brain, and this POT-suppressed cortical activation was also extended to the other extra-striate visual areas V3, V3A, and V4

"The reduced cortical activation in V2 by the POTs may have been responsible for the POT-induced suppression of the illusions and distortions, considering that V2 neurons but not V1 neurons in macaque monkeys respond to illusory contour stimuli," Huang suggests.

The cause of these responses to specific visual stimuli is likely to differ from the photophobia (light sensitivity) migraine sufferers often report during an attack. Going forward, the authors suggest that the specific characteristic of the cortical activation in the extra-striate visual areas they recorded could provide a potential biomarker for identifying those migraine patients suffering cortical hyperactivation. This biomarker could prove useful not only for further evaluation of POTs but also for studying the effectiveness of drugs to prevent migraine.

Notes:

fMRI evidence that precision ophthalmic tints reduce cortical hyperactivation in migraine by Jie Huang, Xiaopeng Zong, Arnold Wilkins, Brian Jenkins, Andrea Bozoki, Yue Cao is published today (26 May, 2011) in the journal Cephalalgia. The article will be free to read for a limited period here.

Source:
Jayne Fairley
SAGE Publications

MAP Pharmaceuticals Submits LEVADEX® To FDA

MAP Pharmaceuticals Submits New Drug Application To FDA For LEVADEX® Orally Inhaled Migraine Drug

27 May 2011  

MAP Pharmaceuticals, Inc. (Nasdaq: MAPP) announced that it has submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for LEVADEX® orally inhaled migraine drug for the potential acute treatment of migraine in adults. According to the National Headache Foundation, approximately 30 million people in the United States suffer from migraine, a debilitating neurological disorder. Common symptoms of migraine include recurrent headaches, nausea, phonophobia (sensitivity to sound) and photophobia (sensitivity to light).

"This NDA submission marks a major corporate milestone for MAP Pharmaceuticals and brings us one step closer to our goal of providing the underserved migraine patient population with a potential new treatment option," said Timothy S. Nelson, president and chief executive officer of MAP Pharmaceuticals. "Our comprehensive development program evaluated LEVADEX in approximately 1,000 patients for up to one year, treating nearly 10,000 migraines. If approved by the FDA, LEVADEX could potentially provide a new treatment option for migraine sufferers, including the millions of patients whose migraines are not well treated today."

The 505(b)(2) NDA submission is based on a comprehensive development program for LEVADEX, and includes efficacy and safety data from the Phase 3 FREEDOM-301 clinical trial that has been presented at scientific conferences and was recently published in Headache: The Journal of Head and Face Pain. In the FREEDOM-301 trial, patients self-administered LEVADEX at home using the Company's proprietary TEMPO® inhaler. LEVADEX contains a novel formulation of dihydroergotamine (DHE). Patients taking LEVADEX in this pivotal trial had statistically significant improvement at two hours compared to patients on placebo for all four co-primary endpoints:

-- Pain relief: 58.7 percent of patients who received LEVADEX compared with 34.5 percent for placebo (p<0.0001);

-- Phonophobia free: 52.9 percent of patients who received LEVADEX compared with 33.8 percent for placebo (p<0.0001);

-- Photophobia free: 46.6 percent of patients who received LEVADEX compared with 27.2 percent for placebo (p<0.0001); and

-- Nausea free: 67.1 percent of patients who received LEVADEX compared with 58.7 percent for placebo (p=0.02).

The most common adverse event reported in the double-blind placebo controlled portion of the trial was medication aftertaste at six percent versus two percent for placebo. The next most common adverse event reported was nausea at five percent compared with two percent for placebo. There were no differences in changes in lung function, as measured by spirometry, between the active and placebo groups.

The 12 month open-label, safety extension of the Phase 3 FREEDOM-301 trial was designed to evaluate overall safety of LEVADEX over six and 12 months of exposure. In total, more than 475 patients completed six months treatment and more than 250 patients completed 12 months treatment. There were no drug related serious adverse events reported in any LEVADEX trial.

The NDA submission also includes data from a pharmacokinetics (PK) trial evaluating the PK and safety of LEVADEX in smokers and non-smokers, a pharmacodynamics (PD) trial evaluating the acute effects of LEVADEX on pulmonary artery pressure, a thorough QT trial comparing the acute effects of a supra-therapeutic dose of LEVADEX on the cardiac QT interval as measured by electrocardiogram and a safety trial in adult asthmatics.

-- Systemic exposure to LEVADEX was not higher in smokers, potentially due to reduced pulmonary absorption, in the PK study comparing smokers vs. non-smokers.

-- There was no difference in pulmonary arterial systolic pressure between the LEVADEX and the placebo group over two hours in the PD study.

-- Results of the QT trial showed that a supra-therapeutic dose of LEVADEX does not increase QTc intervals.

-- PK concentrations for LEVADEX in asthmatics were similar to those in healthy subjects.

About Migraine

Common symptoms of migraine include recurrent headaches, nausea, vomiting, photophobia (sensitivity to light) and phonophobia (sensitivity to sound). According to the National Headache Foundation, most migraines last between four and 24 hours, but some last as long as three days. On average, migraine sufferers experience three migraine attacks monthly, although 25 percent of them experience one or more attacks weekly. The economic burden of migraine remains substantial despite existing treatments, with the direct and indirect costs of migraine in the United States estimated at over $20 billion annually.

Source: MAP Pharmaceuticals, Inc