Botulinum Toxic Injectables to Treat Sialorrhea

Stuart Isaacson, MD: Let’s talk about these botulinum toxic substances. Can you give an idea of why you would uses any botulinum toxic injectable for sialorrhea? It’s not intuitive as we think about or feel the movement disorders using botulinum toxic substances to reduce overactive muscles in movement disorders. Why would it work for sialorrhea?

Richard M. Trosch, MD: The production of saliva is still driven by a neuro response. It’s being innervated by a nerve that is releasing acetylcholine to the gland and telling it to produce saliva. And so although we’re not hitting nicotinic receptors as we are in the case of muscle, we’re hitting muscarinic receptors, but the botulinum toxic substances seem to work on both. So you can reduce production of saliva by injecting the gland with the botulinum.

Stuart Isaacson, MD: The botulinum toxic substance goes to the gland, attaches to the muscarinic receptor, gets internalized, clears the protein, and prevents releasing acetylcholine.

Richard M. Trosch, MD: Right.

Stuart Isaacson, MD: It’s interesting that we’ve thought so much about this as a field to the nicotinic receptor, but botulinum toxin also binds to the muscarinic receptors.

When you think about botulinum toxic substances, we have type A and type B, 2 main types that are available commercially. Do they have any difference in their binding to muscarinic receptors in the gland?

Richard M. Trosch, MD: When they’re acting is a little different. Type A is working on a SNAP-25 protein, and the type B is working on SNARE complex. But the effect is the same. It’s preventing that acetylcholine vesicle from fusing with the synaptic membrane, releasing acetylcholine into the synaptic cleft. So I don’t know that that mechanism makes a difference. There’s some thought that perhaps the type B may be more sensitive to muscarinic receptors, but that’s not really proven, and I think that comes out of the data from the cervical dystonia trials where there was a higher rate of dry mouth, the Myobloc studies using type B compared with the type A products. But we don’t know, and there aren’t really large comparative trials to tell us if type A or type B is the superior toxic substance.

Stuart Isaacson, MD: It’s nice to have choices, though, and have more than 1 type of toxic injectable.

Let’s talk about the botulinum toxic type A injectables. There are several that are available. Do you think these are differential in their effect in treating sialorrhea, or do you group these all together?

Richard M. Trosch, MD: I group them together because I don’t know if they’re really different. They’re different in terms of their complex proteins, but the toxic substance itself is the same. There are different serotypes. We talked about 7 serotypes, and then each serotype has its constraints. The 3 commercially available type A products on the market are serotype A strain 1. They differ. Two of them have complexing protein; 1 does not. But within less than a minute of injection and hitting physiologic pH in the body, the complexing proteins are removed. And so you could say within a minute, these toxic substances are really the identical product—the same light and heavy chain—and should work about the same. Their mechanism of action is not really known to be different. I find they differ in cost, and that tends to drive my use. I try to use the most cost-effective toxic injectable for most purposes. If any type A works they probably all work for this purpose.

Stuart Isaacson, MD: Are these used on label or off label, these botulinum?

Richard M. Trosch, MD: Right now, incobotulinumtoxinA, which is Xeomin, is FDA approved and approved in Europe for sialorrhea, and the other 2 are not. And then we mentioned Myobloc, which is rimabotulinumtoxinB. It is also approved by the FDA in the United States only for sialorrhea.

Stuart Isaacson, MD: Does the indication make you only want to use drugs on label, or are you comfortable using the off-label ones too?

Richard M. Trosch, MD: I’m comfortable off label. If the physician is comfortable with 1 particular product and they just want to use that product, I think that’s fine among the 3 type As. If it works for 1 type A, I think it would work for the other type As.