Welcome to DP Interview.

Today’s topic is botulinum toxin, a procedure that men and women both consider an easy option for wrinkles.

Due to the popularity of the procedure, awareness of the side effects that can occur from its use, especially resistance, has also been rising.

This is not just a problem in Korea, and an international expert committee has been established to study its use without resistance.

Dr.

Michael Martin, who is a member of the committee and one of the world's leading immunologists, is with us today for the interview.

Doctor, I heard that you held a seminar lecture during your visit to Korea.

Could you briefly tell us about your presentation?

Dr.

Michael Martin: BoNT-A is a very valuable pharmaceutical, in aesthetics, here, especially in Korea, it's very important.

But it's also a very valuable drug in therapeutics.

So, you can help, with this drug, people with neurological disorders.

And the problem that can arise when people in aesthetics or therapeutics are treated with botulinum neurotoxin type-A or BoNT-A for a long period of time is that, they can develop a non-response, which sometimes is also called immune resistance.

I like the phrase antibody-mediated non-response better, because that already points to the reason why the problem arises; because these people generate antibodies against the pharmaceutical.

And we can discuss what happens then.

And I explained this morning, how the immune system responds to this pharmaceutical and why it makes antibodies.

As I'm an immunologist, I can try to explain.

Reporter Jung: So you mentioned the issue of antibody-mediated non-response that can arise from BoNT-A.

Is this emerging as an important issue worldwide?

Dr.

Martin: Well, clearly it is an emerging global issue.

Because the number of reports that are dealing with the problem that patients do not respond as well to botulinum neurotoxin treatments after repeated injections – at a weaker response or no response at all – these reports are increasing.

We have had these reports before in therapeutics.

And there are many clinical studies, very good clinical studies, published in very good journals for therapeutics, that show that this problem exists.

And in aesthetics, for a long time, physicians or healthcare practitioners (HCPs) did not realize that this would also be a problem in aesthetics.

But it is becoming a problem and people are aware of this now, and that is why I'm trying to explain how this happens, that antibodies can arise.

May I add one more sentence?

Consider, even if the frequency that is reported for esthetics is relatively low at the moment, please consider there are millions of injections of botulinum neurotoxin performed in the world per year; millions, many millions.

And the number of indications where this pharma-protein is used is continuously increasing.

In addition, the age of the persons that become treated with botulinum neurotoxin for aesthetic reasons, they become younger and younger and younger, especially in the Asian Pacific area.

It's not so much in Europe, but here in Korea and other countries in this area, they become younger and younger.

And therefore, I think it's necessary that we are aware of this problem, and we have to accept that immune resistance exists, and we have to react appropriately.

Reporter Jung: Some may think ‘I will be fine since I only receive local procedures infrequently.’ But as an expert member of the Aesthetic Council for Ethical Use of Neurotoxin Delivery (ASCEND), where a multidisciplinary body of experts from around the world work for the safe use of botulinum toxin, could you correct some of the common misconceptions that we may have? Dr.

Martin: This is a vaccination.

It's nothing else than a vaccination.

And the vaccination, how well the vaccination works, is depending on several parameters.

One is the doses of course of the vaccine.

And one more important is how the vaccine is composed; what is in the vaccine.

We understand that better now.

So, I think it's easier nowadays after the pandemic, to explain what vaccination is about, and why it can happen, that if you inject repeatedly, a bacterial protein, which is foreign to us, why our immune system response.

It's not surprising, it's normal.

And therefore, people should not dispute that they exist.

We should ask why is there a difference between therapeutic indications in reported frequencies and in aesthetic indications in reported frequencies.

And that can be explained why there is a difference at the moment.

Reporter Jung: So resistance is inevitable, but you are studying why it occurs less frequently in aesthetics than therapeutics.

Dr.

Martin: Well, it's absolutely correct, what you're saying, there is a difference.

And we know where there is a difference.

We don't have to really conduct scientific research.

We just have to watch, watch what is going on in the world.

We have to watch what is going on in the Asian Pacific area, and especially also in Korea.

And there are different reasons why there are, at the moment, these great differences between therapeutics and aesthetics.

Why is that?

Because in the recent years, the doses of botulinum neurotoxin used in therapeutics were much higher than the doses used in aesthetics.

This is a few years ago, and it's still true in Europe.

But it's not true anymore in the Asian Pacific area; it's not true in Korea.

Nowadays, the doses that are injected into young people in aesthetics easily, easily, reach the level that is used in neurological disorders in therapeutics.

So, the doses are slowly approaching to be the same, almost.

And we can expect that the frequency of neutralizing antibodies of immune-resistance is continuously increasing.

And it will take a few more months and years till all of these reports come to our knowledge.

I'm absolutely sure that we will see increasing numbers in the next year or two to come.

And Korean federal administration is aware of his problem.

They warned that immuno-resistance can be a problem when treating patients with botulinum toxin type A.

And maybe I can add one more word.

The immune system does not know why the physician injects the botulinum neurotoxin.

The immune system does not know if it is for an aesthetic purpose or to treat a neurologic problem.

The immune system doesn't care.

It senses, how high is the dose.

And very important, it also senses the purity of what you inject.

This is a very important aspect we will discuss, I think, later Reporter Jung: So I would like to how resistance affects the patients.

Could you explain the immunological issues that patients might experience?

Dr.

Martin: It's very easy to understand, when you know how the botulinum neurotoxin works.

It is a molecule that physicians inject, and then the molecule has to be taken up into the nerve terminal into the cell.

And then it works inside of the nerve cell.

Okay?

So, this is important to know.

If a patient...

it doesn't matter whether it's in aesthetics or therapeutics...develops, during treatment, neutralizing antibodies to this botulinum neurotoxin type A, and you inject now into this patients, these antibodies will bind to the toxin, and then it cannot interact with the nerve terminal, with his target, anymore.

So, it's not taken up into the nerve terminal, and it does not perform its function.

So, you inject botulinum neurotoxin, but it never reaches the target, the nerve cell, so there is no effect.

And it depends on the level, how high the level of antibodies are.

If there are not enough neutralizing antibodies to catch all BoNT-A molecules, then you still have a partial response.

If you have a very high titer, very high level of antibodies… It's like a vaccination, similar to vaccination.

If you’re a good responder to vaccination, you have a high level of antibodies, then you don't get sick.

And it's the same here.

If you have a high level of antibodies to BoNT-A that neutralize the injected BoNT-A, it does not work at all.

And this is a problem.

It’s a problem in therapeutics, especially for people with severe neurological disorders.

But it's also a problem in aesthetics because the patients are not satisfied with the result of the treatment.

Reporter Jung: I heard that there are various BoNT-A products available in the market and that the incidence of neutralizing antibodies may vary depending on the purity of the product.

How is it related? Dr.

Martin: As you say correctly, there are different products on the market.

We don't have to name names, we don't have to name these products, but the products differ.

They differ in how they are produced.

They don't differ in the active substance.

The neuromodulator itself is the same active substances, but it differs how they're produced.

And they differ to what extent the companies purify the toxin.

So, we have toxin preparations, where there's only the neuromodulator, the core toxin if you like, and then we have a lot of products on the market that contain additional bacterial proteins that are not necessary for the pharmacological activity, but they remain in the product during the purification process.

All of the products that are produced are produced in bacteria, by bacteria.

And all of the companies take efforts to remove these contaminating proteins.

And some companies stop earlier than others.

Some companies invest a lot of time, a lot of money to have the pure substance, that is sufficient for the job.

And other companies stopped purifying earlier.

And these bacterial components that play no role in the neuromodulation, they can activate the immune system.