BoNT is composed of a core neurotoxin and associated non-toxic accessory proteins (NAPs). The core neurotoxin consists of a 150 kD inactive precursor protein that contains a 100 kD heavy chain and 50 kD light chain, linked by a disulfide bond. NAPs are comprised of hemagglutinin (50 kD) and non-hemagglutinin proteins (130 kD), that associate with the core neurotoxin to help prevent degradation. [5] X Trustworthy Source PubMed Central Journal archive from the U. S. National Institutes of Health Go to source Xeomin (IncobotulinumtoxinA) is the only product where all NAPs have been removed during the manufacturing. [6] X Research source Core and NAPs are further mixed with excipient proteins, which vary among different brands, but include albumin, sucrose, lactose, sodium chloride, and disodium succinate. [7] X Trustworthy Source PubMed Central Journal archive from the U. S. National Institutes of Health Go to source Antibodies against BoNT can be broadly divided into neutralizing antibodies (NAbs), targeting the core neurotoxin, particularly the binding site on the heavy chain, and non-neutralizing antibodies, typically targeting accessory proteins or clinically irrelevant sites on the core neurotoxin and which do not affect clinical efficacy. [8] X Research source
Large doses of BoNT per each injection. Large cumulative dose of BoNT over lifetime. Certain formulations of BoNT (e. g. RimabotulinumtoxinB) Shorter injection intervals, particularly “booster” injections 1–2 weeks after a treatment visit. [9] X Trustworthy Source PubMed Central Journal archive from the U. S. National Institutes of Health Go to source . There aren’t really any other “symptoms” that alert you to botulinum toxin resistance—you simply notice that injections don’t achieve the same result that they used to.
Because botulinum toxin can change the structure of the skin around the injection site, frequent injections in the same area might not achieve the same results. However, this doesn’t mean that you’ve developed resistance—it just means that particular location is no longer a suitable site for injection. [12] X Research source
If your doctor thinks it’s likely that you’ll build up a resistance to botulinum toxin, they might recommend other treatments to achieve the same effect without that risk.
While your “after” photos won’t necessarily look the same after each subsequent treatment, you should definitely be able to tell if the treatment didn’t do anything at all.
The fact that botulinum toxin treatment wasn’t effective doesn’t guarantee that you’re resistant. The only thing your doctor knows for sure is that botulinum toxin treatment doesn’t work for you.
Structural assays, such as ELISA and immunoprecipitation assays (IPA), are sensitive in the detection of BoNT antibodies, but they are unable to discriminate between neutralizing and non-neutralizing antibodies. Bioassays such as the MPA or MHDA utilize animals to identify neutralizing antibodies that impact the clinical efficacy of the toxin. [17] X Research source Blood testing requires experimentation on lab mice, which raises animal rights issues. If you find this problematic, you might want to skip the blood test.
At the same time, studies have also shown that patients tend to develop resistance more often and more quickly with Type B than they do with Type A—so if you’ve already developed resistance to Type A, you’re probably going to end up having the same problem with Type B. [18] X Research source Type B is less potent than Type A, so you can expect the effects not to last as long. [19] X Research source
If you still don’t get the response you want after a second treatment, it’s more likely that you’ve developed resistance. In any case, wait at least a few years before getting any follow-up treatments.
Even after 4 or 5 years, there’s still no guarantee that you’ve completely overcome your resistance and the botulinum toxin will work just as well as it did the first time. However, you have a much better chance of achieving a satisfactory result from the treatment.
Ask your doctor what brands they use and which contain the most purified botulinum toxin. If you’re concerned about developing resistance, you might want to switch to Xeomin as it doesn’t have NAP proteins. [23] X Research source
You can also try using a smaller amount, then coming back a week later for a touch-up. That way, your doctor knows that they’re using the absolute least amount possible.
If you visit your doctor for touch-ups after treatment, wait at least a week after the initial treatment. Don’t go back for another touch-up—instead, wait for your next treatment. If the first treatment wasn’t effective, your doctor can adjust the next treatment so it has a better effect.