Botulinum Toxin Resistance

What is the botulinum toxin?

The botulinum toxin is frequently known as the reason behind botulism. Luckily this is a different form of the toxin. The botulinum toxin is produced by the bacteria Clostridium botulinum.¹ One effect of this toxin’s exposure is reversible muscle paralysis.² People often know botulism as food poisoning, but the toxin has other functions.

Aside from the negative, the toxin has some helpful medical and non-medical uses. The toxin is commonly known as Botox and Dysport. The benefits are to reduce facial wrinkles, relieve pain, and treat movement disorders and muscle stiffness.^2,3 

These treatment products contain the botulinum toxin and proteins that, in some, trigger an immune response. Another familiar product, Xeomin®, contains Clostridium botulinum but without immune-stimulating proteins.^4,5,6 

Types of responses

In some cases, people never experience any benefits from treatments using Botox or Dysport. Botox resistance is rare and is known as a primary non-response.⁷ This type of resistance be due to insufficient dosing, improper product storage, or injection of the product into the wrong area.^5,7 

Another type of resistance is when people who initially benefit from the treatment no longer respond the same or at all. As the effects of the toxin are temporary, multiple treatments are required to maintain the desired result. This type of resistance is known as a secondary non-response.⁷ 

Why the resistance?

The immune system recognizes the botulinum toxin as a foreign substance, so it works hard to clear it away. The body develops antibodies specific to the proteins of the toxin when the immune system kicks in. The antibodies are what block the treatment effects and create resistance.^5,7,8  Secondary non-responders present with more antibodies, supporting the idea of immune system-created resistance.⁹ 

Secondary non-responders often require a higher frequency of treatments.¹⁰ With increased frequency, there is a greater risk of resistance. The greater risk of resistance is due to a higher production of toxin-specific antibodies.¹¹  

Another reason for Botox resistance is that the proteins have been shown to enhance the immune response to the bacteria.¹²  If the immune response is enhanced, the toxin cannot do its job.

Compared to Botox and Dysport, cervical dystonia patients with a secondary non-response later exhibited benefits when switched to Xeomin, which does not have the immune-stimulation proteins.⁶

Fighting Botox resistance

While other factors can result in treatment resistance, it is essential to ask questions about the form of treatment medication and the frequency of dosing that is right for you. It is also critical to do some research to know the right questions to ask about your diagnosis and prescribed protocol. Arming yourself with knowledge can reduce the chances of developing resistance to a crucial treatment option. 

References

1. Davis LE. Botulinum toxin. From poison to medicine. West J Med. Jan 1993;158(1):25-9. https://pubmed.ncbi.nlm.nih.gov/8470380/
2. Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel). Aug 24 2017; 9(9) doi:10.3390/toxins9090260
3. Small R. Botulinum toxin injection for facial wrinkles. Am Fam Physician. Aug 1 2014;90(3):168-75. https://pubmed.ncbi.nlm.nih.gov/25077722/
4. Dressler D, Pan L, Adib Saberi F, Bigalke H. Do complexing proteins provide mechanical protection for botulinum neurotoxins? J Neural Transm (Vienna). Aug 2019;126(8):1047-1050. doi:10.1007/s00702-019-02023-x
5. Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs. Apr 1 2012;26(2):e1-9. doi:10.2165/11599840-000000000-00000
6. Hefter H, Hartmann CJ, Kahlen U, Samadzadeh S, Rosenthal D, Moll M. Clinical improvement after treatment with incobotulinumtoxinA (XEOMIN®) in patients with cervical dystonia resistant to botulinum toxin preparations containing complexing proteins. Front Neurol. 2021;12:636590. doi:10.3389/fneur.2021.636590
7. Bellows S, Jankovic J. Immunogenicity associated with botulinum toxin treatment. Toxins (Basel). Aug 26 2019;11(9) doi:10.3390/toxins11090491
8. Naumann M, Boo LM, Ackerman AH, Gallagher CJ. Immunogenicity of botulinum toxins. J Neural Transm (Vienna). Feb 2013;120(2):275-90. doi:10.1007/s00702-012-0893-9
9. Fabbri M, Leodori G, Fernandes RM, et al. Neutralizing antibody and botulinum toxin therapy: A systematic review and meta-analysis. Neurotox Res. Jan 2016;29(1):105-17. doi:10.1007/s12640-015-9565-5
10. Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord. Mar 1994;9(2):213-7. doi:10.1002/mds.870090216
11. Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology. Sep 1995;45(9):1743-6. doi:10.1212/wnl.45.9.1743
12. Lee JC, Yokota K, Arimitsu H, et al. Production of anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin-haemagglutinin. Microbiology (Reading).Nov2005;151(Pt11):3739-3747. doi:10.1099/mic.0.28421-0