Botulinum toxin (BTX) is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism. The toxin is also used commercially in medicine, cosmetics and research.
They affect 39 million folks in the U.S., 4 million of whom deal with daily pain. Chronic migraines can severely inhibit daily life, and when I started to feel like my bad days were outnumbering my good, I knew I needed to find a solution. Botox had been suggested to me multiple times before by friends, family, and doctors, and though it took quite a while to get it approved by insurance and find a provider I trusted, my migraines were making it hard to live a normal life, so I decided to try it out.
The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide. The heavy chain contains domains with several functions: it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies. The light chain is a zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family which is responsible for fusion. The cleaved SNAP-25 is unable to mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.
On April 6, 2016, the company announced it would partner with Heptares Therapeutics in a deal valued up to $3.3 billion to collaborate on the development of a subtype-selective muscarinic agonists for Alzheimer's disease and other major neurological disorders. On April 21, the company announced the acquisition of Topokine Therapeutics for at least $85 million, gaining the phase IIb/III compound XAF5 - a treatment for dermatochalasis. On August 2, the company sold its generic drugs business to Teva Pharmaceutical Industries for $33.4 billion and 100.3 million shares of Teva. On August 11, the company announced the acquisition of ForSight VISION5 for more than $95 million. On September 6, the company acquired RetroSense Therapeutics for more than $60 million, gaining the positive photosensitivity gene therapy treatment, RST-001. RST-001 is to be used in retinas in which rod and cone photoreceptors have degenerated over time, causing in increase in the sensitivity of light hitting the retina. On September 20, the company announced the acquisition of Tobira Therapeutics for $1.695 billion and, a day later, the acquisition of Akarna Therapeutics for $50 million. On October 3, the company sold Anda, its generic drug distribution business, to Teva for $500 million. On October 25, the company acquired Vitae Pharmaceuticals, focused on dermatology treatments, for $639 million. On October 27, the company announced it would acquire Motus Therapeutics, a developer of treatments for gastrointestinal disorders, for $200 million. On November 22, 2016, the company acquired Chase Pharmaceuticals for an upfront payment of $125 million.
BOTOX is administered about every three months, and must be injected at the site of each nerve trigger, relaxing the surrounding muscles so that they won’t compress the nerve and trigger a migraine. It is a potent drug, and we only recommend using it if other preventative treatment options haven’t helped you. It is generally only administered to patients who have at least 14 headaches a month, or don’t respond to other treatments.
In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A U.S. supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around the world" with less than one gram of raw botulinum toxin. Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the U.S. and other countries.
On November 23, 2015, Allergan and Pfizer announced their intention to merge in a $160 billion transaction, the largest pharmaceutical deal and the third largest merger in history. On April 5, 2016, after the Obama administration announced its plan to ban tax inversions, Pfizer terminated the acquisition and paid Allergan a $150 million breakup fee.
There are eight types of botulinum toxin, named type A–H. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals. Type H is considered the deadliest substance in the world – an injection of only 2 ng can cause death to an adult. Botulinum toxin types A and B are used in medicine to treat various muscle spasms and diseases characterized by overactive muscle. Commercial forms are marketed under the brand names Botox and Dysport, among others.
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Botox should only be injected with sterile instruments in a doctor's office or a medical spa — not at Botox parties at your local nail salon or neighbor's living room. Botox injection is usually performed with some local anesthesia or a numbing cream. You may feel some minimal discomfort from the shot, but today's needles are so thin and fine that the procedure is often painless. Depending on the extent of treatment, the procedure can take anywhere from a few minutes to 20 minutes.
Botulism is an illness caused by a neurotoxin produced by the bacterium Clostridium botulinum. There are three types of botulism: food-borne, wound, and infant. Symptoms include muscle paralysis, dry mouth, constipation, slurred speech, and blurred vision. If food-borne and wound botulism are detected early enough, they may be treated with an antitoxin. Infant botulism is treated intravenously with BabyBIG (Botulism Immune Globulin).
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Tell your doctor if you received any other botulinum toxin product in the last 4 months; have received injections of botulinum toxin such as Myobloc®, Dysport®, or Xeomin® in the past (tell your doctor exactly which product you received); have recently received an antibiotic injection; take muscle relaxants; take allergy or cold medicines; take sleep medicine; take aspirin-like products or blood thinners.
The most commonly reported side effects for JUVÉDERM® injectable gels were injection-site redness, swelling, pain, tenderness, firmness, lumps/bumps, bruising, discoloration, and itching. For JUVÉDERM VOLBELLA® XC, dryness was also reported. For JUVÉDERM VOLUMA® XC, side effects were predominantly moderate in severity, with duration of 2 to 4 weeks; for JUVÉDERM® Ultra XC , JUVÉDERM® Ultra Plus XC, or JUVÉDERM VOLLURE™ XC, they were mostly mild or moderate in severity, with duration of 14 days or less; and for JUVÉDERM VOLBELLA® XC, they were predominantly mild or moderate, with duration of 30 days or less.
Launched in 2002, Practical Neurology is a publication uniquely dedicated to presenting current approaches to patient management, synthesis of emerging research and data, and analysis of industry news with a goal to facilitate practical application and improved clinical practice for all neurologists. Our straightforward articles give neurologists tools they can immediately put into practice.
It’s not just about Botox, though. Last month, the FDA approved the first migraine-specific drug to prevent the severe headaches. Called Aimovig, the injectable med will cost $6,900 a year, according to The New York Times, plus injection fees. Because of the high costs, experts expect the new drug to be subject to step therapy policies. Stephen Silberstein, the director of the headache center at Jefferson University, told me in 2016 that he wouldn’t be surprised if insurance companies required patients to even try and fail Botox before covering the new meds (there are a few of them under development).
Finding an experienced practitioner is particularly important if you’ve never had Botox treatments before as he or she will devise an optimal treatment plan to address your forehead wrinkles. Furthermore, with an experienced, board-certified plastic surgeon you’ll be far less likely to experience any side effects like pain, bruising around the injection site, droopy eyelids, or mistakenly be administered too much Botox, leaving your face looking frozen for the next several months.
Wrinkles, whether they be fine line or deep furrows, typically appear on areas of the body that receive a high amount of exposure to the sun. Smoking, light skin type, hairstyle, the way you dress, your occupational and recreational habits, and heredity are all factors that promote wrinkling. Medical treatments for wrinkles include antioxidants, moisturizers, alpha-hydroxy acids, and vitamin A acid. Cosmetic procedures that treat wrinkles include dermabrasion, microdermabrasion, glycolic acid peels, laser resurfacing, Botox, and fillers.
Botox injections work by weakening or paralyzing certain muscles or by blocking certain nerves. The effects last about three to twelve months, depending on what you are treating. The most common side effects are pain, swelling, or bruising at the injection site. You could also have flu-like symptoms, headache, and upset stomach. Injections in the face may also cause temporary drooping eyelids. You should not use Botox if you are pregnant or breastfeeding.
“I see a lot of patients who come in from sun damage, or who have creases in their foreheads, more lines around the sides of their mouths, crow's feet, and wrinkles on the side of their nose,” Shah says. “At this age, a dermatologist can inject Botox in the right places to help train a person’s face to no longer fall into that habit, which can help decrease the odds that they’ll develop permanent wrinkles in those spots later on.”
Galli has been living with migraine for most of her adult life, but recently, her attacks became more severe and frequent. “My whole life went upside down and nothing was the same,” Galli says, upon being diagnosed with chronic migraine. “The person I used to be wasn't there anymore. I didn't even recognize myself.” To cope with the symptoms that often accompany chronic migraine, Galli found herself retreating to a dark room, waiting for the pain to pass, but it never did. In response, Galli says, she asked herself what she could do to feel better but also share her story. “Everyone around me that knew how high energy, and how much of a go-getter I am, asked what was happening? Where was that person?” When she came across the announcement of the Migraine Moment Film Contest, she saw it as her opportunity to bring awareness about what it is like to live with migraine and bust the misconceptions surrounding this invisible disease. Enter: “Invisible Hero.”
Botox prevents migraine headaches before they start, but takes time to work. “I look to the second and third treatments to maximize effects,” says Dr. Andrew Blumenfeld. “Patients see increasing benefit with an increase in the number of treatment cycles.” One treatment lasts for 10-12 weeks, and patients reported that two Botox treatments reduced the number of headache days by approximately 50%.
Calcitonin gene-related peptide (CGRP) is a neuropeptide found all over the body, says Dr. Amaal Starling, an Assistant Professor of Neurology at the Mayo Clinic in Phoenix. This neuropeptide attaches to a receptor called a CGRP receptor. CGRP and its receptor are involved in numerous bodily processes—from gastrointestinal movement to the transmission of pain. Over the past few decades, there has been increasing evidence that CGRP plays a role in both migraine and cluster headache. During a migraine attack, researchers have found increased levels of CGRP in patients’ blood and saliva. They discovered migraine medications like sumatriptan reduced levels of CGRP in patients living with migraine. They also found that patients with chronic migraine—meaning 15 or more migraine days per month, eight of which either meet criteria for migraine or are treated with migraine-specific medication—had chronically elevated levels of CGRP. In addition, recent research found that giving a patient with migraine an infusion of CGRP would lead to a migraine-like attack. “All of these studies led to the hypothesis that CGRP and its receptor play a key role in migraine, as well as in cluster headache,” Dr. Starling says.
Many times, effects on spasticity are longer lasting. It is not clear if this is due to breaking down patterned movements (many muscles contracting together rather than singly) or from allowing weak muscles to get stronger over time (that were overpowered before by more spastic muscles pulling against them). It is vital to have close follow-up after the injections to figure out the best course of treatment.
Kybella helps patients lose their dreaded double chin and regain the taut, sculpted profile of their youth. The ingredients in Kybella are naturally made by the body, which means that you’re very likely to be satisfied with the results. It works by destroying the fat cells under the chin, making them unable to store fat any longer. Each treatment only requires 15-20 minutes, which leaves enough time to grab some sushi before you head back to the office. You’ll pay out somewhere between $1200 and $1800, but a chin tuck can cost anywhere from $1500 to $4000. Plus, Kybella doesn’t require the healing time that traditional skin liposuction does.
Allergan PLC (AGN) is a large market cap ($65B) biopharmaceutical company with a pipeline of innovative and generic therapeutics for diseases affecting the eyes, bowel, lungs, skin, urogenital systems and brain. Through the acquisition of Tobira Pharmaceuticals and its assets including cenicriviroc (CVC), Allergan is one of the leaders in the clinical development of anti-NASH therapeutics (the focus of this article).
I don’t know what’s harder, being a mom or living with migraine. Having both can be overwhelming. Over the years, as a stay-at-home mom of two and chronic migraine fighter, I have learned to adapt my life and my children’s lives to migraine. I alter my family’s schedule around my children’s naps, meals and moods, while also keeping in mind my migraine attacks, sensitivities, triggers and abilities.
There have been reports following administration of BOTOX® of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease. Use caution when administering to patients with pre-existing cardiovascular disease.
Some service providers offer financing options to make the procedure affordable. The Botox Cosmetic product is eligible for the Brilliant Distinctions Program that helps the members through savings, rebates, bonus points, and other perks. But there are also some providers with their own rebate program that gives a discount on the next procedure by 10% to 25%. Coupons are available in forms of discount, promo or free service for loyal customers. Also, a large volume of Botox used in the treatment, there is a possibility to avail discounted price of the Botox per unit.
I’ve had migraine since I was 5 and have learned a lot over the years about how to manage it. I’m aware of the foods that trigger my migraine attacks, and I try to eat consistently and drink a lot of water. My children and I eat as healthy as possible throughout the day to keep energy up, knowing skipped meals are a trigger for both tantrums and migraine attacks. Staying on a schedule allows my body to stay stable and helps me identify triggers. The same goes for my children. Maintaining their energy and providing them with good food and water prevents them from getting “hangry” later. We all want to avoid a food meltdown. I know that I am triggered by weather, hormones, stress, diet, hydration, light, sound, heat, sleep and more. I try to be prepared for as many of these situations as I can, but some are easier to avoid than others. If you’re unaware of your triggers, keep a log. There are migraine apps that can help you track your symptoms and identify what’s causing your attacks. Finding patterns in how you react may help with identifying effective medications or alternative treatments.
There's been a pivotal shift in how women in their 20s look at their faces. And while the reasons are arguably as multi-faceted as this new generation itself, many would agree on one thing: The impact of social media, from selfies to YouTube videos to meticulously crafted Snapchat and Insta Stories, combined with endlessly retouched photographs in magazines and ad campaigns, can not be underestimated. From the constant stream of supernaturally smooth jawlines and chiseled cheekbones to celebrity plastic surgeons posting before-and-after images of their work, the age of 24/7 self-documentation has spurred a novel set of beauty ideals—and, with it, a dramatic increase in cosmetic procedures. For 20-somethings, there's no treatment more popular—or controversial—than Botox. Need proof? According to the American Society of Plastic Surgeons, botulinum toxin procedures have increased 28 percent since 2010 amongst 20 to 29-year-olds.
Treatment with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure.
Botox essentially paralyzes the muscles and stops them from contracting. Results are visible within one week after treatment and remain for a minimum of three months. Some surgeons suggest that Zytaze, a new prescription zinc supplement, can extend these results if taken in the days leading up to your Botox injections. Ask your doctor about Zytaze before your next Botox injection.
It is not always clear what is causing chronic migraines. BOTOX is a viable option for treating migraines, and it may be the most effective treatment for you. Migraines lead to extreme pain that impacts every aspect of life, from personal to professional. Migraines are debilitating and for some who suffer from the condition, bedrest is the only option. A BOTOX treatment for migraines is a simple procedure but could vastly improve your quality of life.
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army’s Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and generously provided it to the academic community.
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Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, the electrical signal from an activated muscle, to guide injection) of local anesthetics as a diagnostic technique for evaluating an individual muscle’s contribution to an eye movement. Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by Daniel Drachman’s work with chicks at Johns Hopkins, Alan B Scott and colleagues injected botulinum toxin into monkey extraocular muscles. The result was remarkable: a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side-effects.
Duration of response was calculated as the number of days between injection and the date of the first visit at which patients returned to 3 or 4 on the HDSS scale. The median duration of response following the first treatment in BOTOX treated patients with either dose was 201 days. Among those who received a second BOTOX injection, the median duration of response was similar to that observed after the first treatment.
In clinical trials, 30.6% of patients (33/108) who were not using clean intermittent catheterization (CIC) prior to injection, required catheterization for urinary retention following treatment with BOTOX® 200 Units as compared to 6.7% of patients (7/104) treated with placebo. The median duration of post-injection catheterization for these patients treated with BOTOX® 200 Units (n = 33) was 289 days (minimum 1 day to maximum 530 days) as compared to a median duration of 358 days (minimum 2 days to maximum 379 days) for patients receiving placebo (n = 7).