Botulinum toxin may travel further than expected in nerve cells
The botulinum toxins are among the deadliest substances on Earth, and two specific toxins — including the popular drug Botox — have multiple uses for treating many neuromuscular conditions, including frown lines, disabling muscle spasms and migraine headaches.
The botulinum toxins cancel nerve signals to the muscles, creating paralysis that can last for months. Given its extraordinary toxicity, doses are typically measured in trillionths of a gram, and targets are carefully chosen to silence only the desired motor nerves.
When Botox and related botulinum drugs entered the market, “the idea was that they are safe to use, they stay where they are injected, and you don’t have to worry about toxin going to the central nervous system and causing weird effects,” says Edwin Chapman, an investigator at the Howard Hughes Medical Institute and professor of neuroscience at the University of Wisconsin—Madison.
The concern that this powerful toxin can move beyond the injection site was reinforced in 2009, when the Food and Drug Administration added a prominent warning to prescribing information “to highlight that botulinum toxin may spread from the area of injection to produce symptoms consistent with botulism,” including “unexpected loss of strength or muscle weakness. … Understand that swallowing and breathing difficulties can be life-threatening and there have been reports of deaths related to the effects of spread of botulinum toxin.”
Additionally, physicians have seen puzzling results from treatment, adds Ewa Bomba-Warczak, a doctoral candidate in neuroscience. “In many cases, after an injection for a disabling spasm of neck muscles called cervical dystonia, there is no change in muscle tone but the patient finds relief and is perfectly happy. That result can’t be explained by the local effects.”
In a study published today (Aug. 4, 2016) in Cell Reports, senior author Chapman, first author Bomba-Warczak and colleagues present clear evidence that toxin is moving between neurons in a lab dish.
The study looked at mouse neurons in wells connected by tiny channels that allow growth of axons — the long fibers that neurons use to communicate.
In tests of two botulinum toxins, the researchers saw toxin molecules entering the injected cell, as expected.
Once inside a neuron, botulinum toxin cleaves proteins responsible for fusion of chemical containers, known as vesicles, with the plasma membrane. This fusion event releases chemical signals that underlie communication with muscles, and the inability to fuse leads to the temporary paralysis caused by botulinum toxin.
Using antibodies to identify fragments of the damaged proteins, Chapman’s group showed that toxin molecules were moving to nerve cells in wells that had not initially received the harmful molecules. “Every time one fraction of the toxin acts locally (on the first nerve cell it contacts), another fraction acts at a distance,” says Chapman. “It’s unknown how far they travel, which likely depends on the dose of toxin and other factors.”
Co-author Jason Vevea, a UW–Madison postdoctoral fellow, produced videos showing tagged molecules of botulinum toxin moving along the axons connecting neurons.
Botulinum toxins were first described in the 1800s, and have long been a subject of research at UW–Madison. Allergan PLC, which markets four versions of botulinum toxin, reported global Botox sales of nearly $2 billion in 2015.
By finding that toxin molecules don’t always stay where they are injected, Chapman says the Wisconsin study answers a long-standing question about mobility, but raises several more. “We have seen that these toxins enter neurons at the injection site, causing the desired local paralysis, but Ewa and Jason have shown unambiguously the existence of a second entry pathway that takes some of the toxin molecules to other neurons.”
The research, done in a lab dish, removes variables that have plagued similar studies performed in animals, Chapman says. “We wanted to see if we could build an in vitro (in a dish) system that allows direct visualization of this putative movement, in a way that’s simple, easy to interpret, and unambiguous. Do they move, or do they not?”
Chapman wonders about the effects of extraordinarily powerful toxin molecules that travel the neural networks. Local effects have, until now, been deemed the sole effects. But could part of its effects be due to the transported toxin?
“It’s an exciting prospect, supplanting a $2 billion drug with a safer drug.”
These questions could be answered by genetically engineering the Clostridium bacteria that make botulinum toxin to alter the toxin’s structure, Chapman says. “We may be in a position to mutate the part of the toxin that attaches to a receptor on the neuron so it can only enter the local pathway, not this new pathway we have described.”
If only the local effects matter for medicine, tomorrow’s versions of this ancient toxin molecule may be able to alleviate symptoms from wrinkles to severe muscle spasms without moving beyond the target neurons.
“I have a hard time imagining that any physician is going to want to inject something they know can move about when they have an option to use something that stays put,” Chapman says. “It’s an exciting prospect, supplanting a $2 billion drug with a safer drug.”
– See more at: http://news.wisc.edu/botulinum-toxin-study-proves-possibility-of-remote-effects/#sthash.rA51isuY.dpuf
Hi Lavoris, I tried to reply to your post, but it wouldn’t let me. So, Im replying here. I private msg’d you with my contact info.. I’m in the Los Angeles area. I look forward to hearing from you..
Is there anyone located in Oregon with advice for ongoing adverse affects from Botox? I have been to every doctor I could get in to. GP, neurologist, Psychiatrist, ER . None of which have any ideas, answers or advice. I suffer from severe anxiety, aches in my bones, muscle atrophy, weight loss (40#), no appetitive, chest pain, and nausea. I am 6 months out from last Botox injections. Will this ever end? This is truly a nightmare. If only there were a doctor that would show an interest in figuring this out. I have called Allergan several times. Their answer, “We recommend you contact your provider for this, we have no data to support your symptoms.” Oh my gosh! Is there any research going on? It seems there are a lot of people suffering.
Someone, please help!
Is there anyone out there in Los Angeles? Three months ago I had injections and three weeks later I had tingling in my toes and fingers. I went to the Dr. and told him about this and he pulled out the pamphlet and said there was nothing in there about that. Well, actually, there is. It’s a side affect of overdose which is something I didn’t realize at the time. Since then the tingling and nerve pinging spread through my small fiber nerves. No muscle damage, but from what I hear that’s actually preferable. I had a non cancerous skin spot turn cancerous suddenly with nobody thought was connected, but now I have another one. The Derm checked my face two weeks ago and it was fine and now I have basal cell again. My ANA is through the roof without a diagnosis. I KNOW what this is. Nobody believed me at first and now the Drs. are caving. Unfortunately not one of them knows what to do. One of them sent me to some Dr. who has a website but no recommendations and sounds a bit wacky and is out of my budget. A budget which has nearly bankrupted my family through CT scans and MRIs and blood test and x rays. Does anyone have any protocol they can recommend or words of encouragement. I am about to enter NPI, the Neuropsychiatric Institute at UCLA for help because I can no longer cope and my family feels helpless. Does anybody have any words of comfort or advice for me?
I am 13 months in and am having a bad flare up at the moment. My relapses usually last about 5 days to a week but this one is over 4 weeks now . It always starts with bad anxiety and then as the anxiety subsides all the eye, ear and brain and nerve symptoms kick in. I have tried almost every supplement and vitamin known to mankind to rid my body and brain of this toxin . Besides Sxeletium Seraphos and Picamilon which I take for the anxiety nothing else seems to help and I am very sensitive to most pharmaceutical drugs. Benzos for instance do not work at all on me . Many pharmacetical SSRI.s for instance only work on about 70 percent of people so the rest of us need to find alternatives. I have recently tried cannabis oil but it does not help either. I have decided that I might try Ayahuasca. It is an ancient South American potion that has been used as a powerful healing substance for thousands of years and there is now renewed interests in its amazing healing properties. It has been successfully used to treat psychological/emotional issues such as ptsd, depression and anxiety but there is now some fairly concrete evidence that it seems to have had some good results on many physiological issues. The Ayahuasca is administered in a controlled environment by experienced practitioners and is relatively safe when proper diet and pre-preparation has taken place . As botox poisoning affects the mind body and soul I think there would surely be some benefit in this treatment. I am researching on how the Ayahuasca may react with the botox itself but not much is available on the subject. I am going to contact some clinics abroad to discuss this with people who may have some idea. Ayahuasca is illegal here in the UK but legal in many other countries which have these clinics. . At this point legal means nothing to me as botox is legal and is deadly so my mindset has changed drastically as to who one can trust. Pharmaceutical company pressure probably got Ayahuasca banned in more corrupt countries like the UK and US where lobbyists grease politicians palms handsomely. It works and cant be patented…shock horror. Sorry to rant but I hate the fact that much research is blocked by big pharma scared of losing profits. I work in mental health so am very aware of what goes on as far as banning of substances that cannot be patented are concerned. Oh well I will update when I find out more. I am at the point now where I will try anything to get rid of this hideous poison I have mistakingly put in my body over and over again .
Last week I posted about small fiber neuropathy after xeiomin injections three months ago. A week ago I realized that when I cried (over this and my old life being gone) no tears come out. I am going to the eye dr. today, I tested negative for Sjogren’s and my eyes are not dry, but my gland doesn’t seem interested. I am so terrified that this is also the Botox and that the damage is spreading to other areas of my body. I have an appointment with an endocronologist in September but I am so frightened that I have killed myself. I went to a new Dr.. who is very well known but he was very aggressive with treatment. I look great, but I am afraid I am slowly and painfully dying. Can anyone please console me? I am having very very bad thoughts. Will this ever end or is this just the beginning? I can’t live this way, always afraid, always in pain, scared of the next problem. I am now on lyrica, which helps a little and Ativan for anxiety. I am so ashamed and wish I had a time machine so I could slap myself. I was happy with the way I looked before and never should have gone to someone new. I had a bad feeling when I walked in and I did it anyway.
was anyone tested for immune complexes ? One doctor suggested plasmaferesis, did anyone try that maybe?
just curious about this?
Bones, Muscles and Fat
Klaudia007, will you tell is more a out the Polish lady and what has happened to her bones, muscles and fat? I tried to respond to your post but it didn’t work. Thank you, Klaudia007.
I received botox injections on december 1, 2014 and my life has not been the same since.
In first year I didnt get much help from polish doctors. Despite the fact I had result from my blood test (toxin was found in my bloodstream 7months after injection) they lied to me that Im completely healthy person and I have mental problems! I was treated like piece of trash!
In second year I got the medical documentation which confirmed my symptoms and showed that all my neurological issues are connected with botox intoxication.
Now i was diagnosed with polineuropathy, muscle and fat atrophy and also brain damage (demyelination).
My face and head are sunken and small, my body has also been affected. My cheeks dropped, I got sunken temples, my nose got smaller, my eyes were smaller, even my forehead is flat now. The sides of my forehead and head are totally sunken. ALL OF THE FAT IS GONE FROM MY FACE.
NOW im making more testing to check for autoimmune disorders. I also have many neurological symptoms like dry eyes, head pain, muscle weakness etc. Im worried that I have fat necrosis.
As you can see Im totally destroyed. I think I will put here some pictures of my “new face”, but believe me I LOOK DRASTIC NOW, LIKE I HAVE ANOREXIA OR SOMETHING. My polish neurologist told me that there is a risk that I WILL DIE FROM SERIOUS BOTOX SIDE EFFECTS. IM ONLY 31.
I found 53 old woman from Poland. She is 7 years after injections now and had similar symptoms to my in HER 2nd year. SIMILAR TO MY SYMPTOMS AND VERY UGLY (VERY UGLY I LOVE YOU;)). SHE FEELS MUCH WORSE NOW!!
Her body and face didnt back to normal. The toxin destroyed even her bones!!
Its a horror.
I am at the end of my rope. I am not getting much traction on here so I will keep it simple. Benedryl seems to help a fraction at night-calms me down a fraction after a day of suffering. Is this safe to use?
Hi everyone, I had an injection 4 months ago and my life was turned about upside down, 3 days after major stuff started: chronic insomnia(going from sleeping 9 hours a night), heart palps/racing, anxiety/panic attacks (never had them in my life), muscle twitches and lots of other symptoms.
When I reported this to the clinic that did the Botox injection they have filed a report with Allergan around this around my main symptoms – but said there are NO reports with the same symptoms as me reported with Allergan?? I keep reading most of you have reported this, so why wouldn’t they have reports around insomnia, brain fog, anxiety etc.
Feels like Allergan is keeping some closed doors to protect themselves?:( Money speaks maybe?
It was insinuated by the clinic that people on these boards are just people with other symptoms using Botox as a scape goat.
Is there anyone that has been to a doctor who has been able to point to Botox being the culprit?
Does anyone know were I can find more info? I tried to ask a couple of questions here the other day.
- Hi all just wanted to post an update. After my initial Hell I was evaluated at Mayo where they came to the conclusion I was suffering a severe dysautonomia. I was diagnosed with Pots. While some things did seem to improve (digestion, tremor, blurred vision), I still suffered with vascular tone and muscle weakness. When I stand up all the blood pools in my extremities. When I could no longer handle dragging my legs around before feeling like I was going to pass out, I had several veins in my legs ablated (EVLT). This significantly improved my tolerance for standing. I have noticed small, but slow improvements. I have also had to work full time. The first year I did not think I would make it. I am doing better now. I continue to use massage, acupuncture, and reflexology. I take pyridostigmine and propranolol daily and exercise as much as possible. I also take collagen, pycnogenol, and wear compression gear. I keep hoping for improvements and live each day the best I can:) Best wishes.
If I were to google botulism I do not have the symptoms I do have lots of migraines an brain fog however . Do I have botulism?
Also why do so few get this, while most do the same exact thing and amount in same place and are fine?
I would appreciate very much hearing from those of you who bega to experience insomnia shortly after botox injections. I went from being a very healthy sleeper, to having insomnia, from one day to the next. It was like a light switch was turned on. I had injections two months ago and have a few other symptoms. All have improved a slight bit, but not the insomnia. The only improvement is that I can sleep 4 hours straight if I take 10 mg. of ambience (I tried with some of my husband’s).
It would be encouraging to hear from some of you who have struggled with insomnia, how you’re doing, what has helped, etc.
Thought I’d post this to you all as it just came into my inbox…not good news… it validates the use of botox for chronic migraines and says nothing about side effects. My guess is botox treatment for headaches will simply increase because of it. I haven’t read the guidelines associated with the news, but thought some of you might want to. Here is the link:
Sono Passati 3 anni dall’iniezione di bottox Sono 6 mesi Che i Disturbi Sono insopportabili Qualcuno mi quo osare un consiglio Un aiuto Qualcuno sa dirmi se i Disturbi alle gambe alla Respirazione al occhio scompariranno Completamente?