Botulinum Toxins and Friends
(Ed Note: This is from an article written several years ago and provides a very good description of the various toxins).
Botulinum Toxin and Friends
We now have at our disposal a new tool to fight spasmodic torticollis and dystonia. This new product is called MyoblocT from Solstice Pharmaceutical. MyoblocT is the first commercially available preparation of Botulinum toxin type B.
With growing numbers of individuals injected and treated with the botulinum toxin A, BOTOX®, there has been an equal concern for some individuals who seem to develop a resistance to the use of the medicine after a period of time. A common theory holds that after exposure to the botulinum toxin in high amounts or frequent dosages, one develops an immunological response that blocks its usefulness. This has led some investigators to search for other botulinum toxins, which are immunologically different, but possibly still effective.
Patients who initially respond to botulinum toxin A and then develop some resistance to its effects are known as secondary nonresponders. There are some individuals who do not respond to botulinum toxin A. These individuals are considered primary nonresponders. A primary nonresponder will more than likely not respond to any of the other types of botulinum toxin.
There are eight distinct or different types of botulinum toxins that can be identified immunologically. They are A, B, C1, C2, D, E F and G. These types of neurotoxins come from a microscopic bacterium, Clostridium Botulinum (gram positive, spore forming bacillus) and several of its close cousins. The different types of human food poisoning usually comes from the types A, B, or E. The last time you had food poisoning from Alaskan king crab seafood, it may have been type E. The other types of botulinum toxin affect other critters. A little of this stuff goes a long way. As little as 0.1 to 1.0 micrograms can kill a human being. Except for Alaska, vegetables are the cause of botulism in 70% of the cases of food poisoning in the continental US.
Botulinum toxin F has been shown to be effective in secondary nonresponders, those who have stopped having a good clinical response to botulinum toxin A. However, its duration of action is much shorter than botulinum toxin A, lasting only a couple of weeks. Botulinum toxin type A or BOTOX® (Allergan) has been available since 1989. There is another preparation of botulinum toxin type A from Europe known as Dysport® (Speywood). The other player in the game is Myobloc T ( Solstice Pharmaceutical). The new preparation will be the first commercially available preparation of botulinum toxin type B. Dysport® may also become available if approved by the FDA.
Making comparisons between these different substances needs to raise a note of caution. There are no large comparisons of the medications in head-to-head studies. Most of the studies have compared the relative effects on mice. Thanks to the mighty mouse, Mickey and his friends excluded, there are some comparisons that can be made. The preparations of Dysport® are a little weaker when compared to BOTOX®. Remember, both of these are botulinum toxin type A preparations. The ratios varies slightly with one unit of BOTOX® equal to approximately 3-5 units of Dysport®. MyoblocT is botulinum toxin type B and is not directly comparable to the type A botulinum toxins. Indirectly by measuring the effects on mice, an estimate can be made. It will take 50-100 times the dose of MyoblocT to be as effective as BOTOX®. This suggests that about 10,000 units of MyoblocT will be equal to 200 units of BOTOX®.
The two different types of botulinum toxins, A and B, work at two different sites of the neuromuscular junction. This is the place where the nerve meets up and connects with the muscle. Little packages of chemicals (neurotransmitters, specifically acetycholine) are manufactured in the nerve. This is the manufacturing step. When the nerve is stimulated, the little packets (vesicles) are released and then travel to the muscle. When they arrive at the muscle, the muscle knows to contract or shorten. This is the distributing step. Botulinum toxin A works to stop or slow down the packing of the bundles of neurotransmitters (manufacturing). Botulinum toxin B works to stop or slow down the release of the packets once they are made (distributing).
Recent information suggests that MyoblocT will come in several different dosage vials including 2,500 units, 5,000 units, and 10,000 units. Most of the clinical outcome information was based on using a dosage of 10,000 units. With that dosage, the duration of the botulinum effects lasted for about 10-12 weeks. The most significant side effects were dry mouth and difficulty swallowing. There may be more patients who experience side effects on the MyoblocT on a percentage basis.
It is also important to note that late in 1997, Allergan, the maker of BOTOX®, went to the FDA to get permission to change the manufacture and processing of their product. This allowed them the opportunity to decrease the overall protein load that accompanied the active toxin. Each vial of BOTOX® contains the toxin itself and several other proteins. In changing the process, the overall method reduces the amount of extraneous non-toxin protein. In doing so, it was hoped that by reducing the foreign proteins, there would be less of a chance for the development of an immunological reaction that would lessen the response of the toxins. Some of the animal data helps support this claim. Therefore, with the newly formulated BOTOX®, there should be less numbers of people who develop the blocking antibodies suspected of inactivating the medicine!
James Auberle, M.D.
Medical Director, ST/Dystonia
My mom and I wanted to thank you for hosting such a great symposium this year. This was our third year and we are looking forward to next years. E. Mathews