[Neurology Story] Interview with Professor Shin Chan-youngㅣA new approach to ADHD and ASD treatment

22-05-20

In recent years, interest in ADHD and autism has increased. It is no longer strange to encounter the words 'ADHD' or 'autism' in the media. Among domestic books related to ADHD, books published within the last three years account for a quarter of the total.

'Is it my child?' Or interest in 'maybe me?' is leading to interest in information about diseases and treatments. To be clear in advance, there is no 'perfect' treatment for brain development disorders such as ADHD or autism.

In this article, through an interview with Professor Shin Chan-young, a professor at Konkuk University Graduate School of Medicine and CEO of Neuroventi, a brain development disorder treatment development company, we examine what ADHD and autism are, and find out how to treat them through a new approach.

| Brain development disorders that are no longer unfamiliar, ADHD and ASD

Q. How is ADHD defined?

Developmental disabilities can only be defined by symptoms. In the case of ADHD (ADHD, Attention Deficit/Hyperactivity Disorder), there are three core symptoms. ADHD is a developmental disorder with three symptoms: hyperactivity, attention deficit, and impulsivity.

ADHD has a high prevalence. It is said that it is usually between 8 and 12%, but it is serious enough to affect one in 10 babies born.

ADHD has been considered to be ‘a developmental disorder only in children’, but since about 10 years ago, the problem of ADHD in adults has been on the rise. The most common symptom in adults is attention deficit rather than hyperactivity. Hyperactivity naturally diminishes with growth, but attention rarely improves. Currently, it is known that about 4% of adults have adult ADHD.

Q. How is ASD, commonly called ‘autism’, defined?

ASD stands for autism spectrum disorder (ASD). By “spectrum,” we mean that the symptoms are very diverse. It is one of the developmental disorders that show various and complex symptoms. Like ADHD, ASD has core symptoms. Core symptoms are divided into two main categories.

One is that social communication is difficult. They often have difficulties with both verbal and non-verbal communication. For example, if you have difficulty using pragmatic language, on a holiday, when a relative asked, ‘Why are your mother’s hands so big?’, she would ask, meaning ‘She cooks a lot’. However, in the case of ASD, the reaction is ‘My mom’s hands aren’t big?’. Difficulties in general communication. The categories of communication that are difficult are both verbal and non-verbal.

The second characteristic is homologous behavior. It is characterized by repetition of the same behavior. ASD is diagnosed when both of these characteristics are present.

Another thing, I talked about ‘spectrum’ earlier. These symptoms range in severity from very mild to severe. In addition, ASD shows various accompanying symptoms in addition to the above two symptoms. As many as 30% of people with ASD show hyperactivity. It's called 'like behavior' of ADHD, but it's not strange to classify it as ADHD. In severe cases, ADHD symptoms may need treatment.

ASD can coexist with ADHD symptoms on a wide spectrum, or it can show seizure symptoms. It may also accompany other symptoms, such as depression, paranoia, anxiety, or obsessive compulsions.

Q. What are the causes of ADHD and ASD?

There are both genetic and environmental factors.

Both ADHD and ASD are disorders with a high genetic predisposition. Scholars vary in what percentage they believe to have a genetic predisposition, but it can range from 60% to 80% for ADHD and from 50% to as much as 90% for ASD.

However, there is something to be aware of in these genetically-driven conditions. When it comes to heredity, we think that parents originally have predisposition factors. Of course, there may be such a part, but there are more studies on new mutations called “de novo mutations (new mutations in gametes or somatic cells).” During pregnancy, new mutations may occur in the sperm or egg, which can affect the unborn child.

Environmental factors have also been studied extensively. For example, there are studies that show that various environmental factors, such as alcohol, tobacco, food additives or preservatives, drug effects, and fetal effects due to infection during pregnancy and surrounding environmental factors, have an effect.

As such, developmental disabilities are complexly intertwined with genetic and environmental factors.

Q. What are the existing treatments?

There is no cure for developmental disorders completely. Currently, there are treatments available that help improve the aforementioned core symptoms.

In the case of ADHD, abnormalities in neurotransmitters such as dopamine and norepinephrine are pointed out as a direct cause of ADHD symptoms. A treatment that improves the function of these neurotransmitters and enables people to concentrate is being used.

In the case of ASD, there is no cure, so we proceed with behavioral cognitive therapy. Behavioral cognitive therapy is known to be effective when received from a young age, so the importance of early diagnosis is considered high. It is said that the human brain develops until the age of 25, but because it develops more at a young age, behavioral cognitive therapy at such a sensitive time is likely to be more effective.

Recently, papers have been published showing that even 3-month-old infants can diagnose to some extent. At the pediatric department, infants and toddlers are examined at regular intervals. If you have any observations from your parents, it is recommended that you seek counseling or visit a specialist for help during the examination. If you have symptoms such as not responding when you call your baby's name at home, seeing a smiling face and not responding to it, or not answering your name when you are a little older, you need to be diagnosed by a specialist. there is.

| A New Approach to Treatment of Brain Developmental Disorders

Q. What kind of environment should be created for ADHD and ASD treatment?

It is very important to understand and support brain development disorder diseases for the nation and society as a whole.

There is an atmosphere of social concealment about having a developmental disability. For example, even though there are medications for ADHD, only about 5% of them were prescribed 10 years ago. Now, it has risen to about 15%, but it is still low compared to developed countries where the prescription rate reaches 50%.

Investments from the government and private companies are also important. In recent years, the problems of neurological and psychiatric diseases have increased, and the government is taking a drive. However, there is a lack of movement to follow this at the level of private companies. There are quite a few new drug development companies in Korea, but when you look at how much our domestic pharmaceutical industry or venture companies are investing in and developing developmental disabilities and psychiatric diseases such as ADHD and ASD, I think they are quite lacking.

Q. How is Neuroventi approaching drug development?

We have an approach to develop substances that induce optimal effects and minimal side effects by well profiling various receptors and targets involved in the mechanism of action and side effects.

Traditionally, drug development has been carried out with drug development for a single target substance (Single Molecule Targeting). It is to develop a substance that has an affinity of Sub-nano molar (effective concentration unit) by setting a target and increasing the affinity (here, the force that binds to the receptor) to it. In other words, it is to selectively and strongly adjust one of the most important targets.

However, this method does not work well for the CNS (central nervous system). It is necessary to understand the characteristics of neurological and psychiatric diseases. Neuropsychiatric diseases have ten times more complex causes than other diseases. It is very difficult to target because it is a psychiatric disease that is caused by a mixture of various causes.

In addition, even if a formulation is developed and applied with a single targeting, severe side effects may occur. It also helps maintain normal neurological and brain function, so when you shut something down forcefully, it has side effects. In addition, there are many cases in which multiple receptors or proteins are involved in a single brain function and finely controlled, so it is often difficult to achieve a dramatic therapeutic effect by controlling only one brain function. If two or three protein targets that control hyperactivity symptoms are simultaneously and effectively controlled at an appropriate level, a therapeutic effect will appear, but there are not so many means to simultaneously control them pharmacologically.

So, it seems that the development of drugs for a single target substance in a very classical, traditional way is now impossible in the field of psychiatry. All those drugs are already out there. Now, it seems that it is important to design elaborately in which direction the targets are optimally adjusted.

Q. Specifically, I would like to know what pathogenesis factors and mechanism of action are used for the agents currently under development by Neuroventi.

- ADHD

Existing treatments increase the activity of two neurotransmitters, dopamine and norepinephrine. Although therapeutically effective, it can lead to addiction and dependence. In addition, there are great concerns about side effects such as increased blood pressure, decreased appetite, and stunted height growth.

Another class includes agents that activate only one of the two neurotransmitters. However, there were opinions that it was less effective than drugs that simultaneously regulate two neurotransmitters in clinical practice.

We focused our attention on another neurotransmitter called serotonin. As is well known to the general public, serotonin affects various areas such as concentration, memory, and improvement in depression. We are developing a drug that modulates dopamine, norepinephrine, and serotonin at the same time. In this way, the amount of drug can be reduced, so it is believed that the risk of side effects can be reduced while the effect can be increased.

-ASD

As a recent trend that has emerged through research related to the development of ASD treatments, a significant part is that the norepinephrine and serotonin systems are very important in relation to the development of ASD treatments.

You may think that dopamine and serotonin overlap with ADHD treatment mentioned earlier, but which receptor works and how it works is slightly different for each disease. Receptors themselves have very diverse targets. There are 5 subtypes of dopamine receptors and 17 subtypes of serotonin receptors. There are many people who study which of these receptors need to be raised and lowered to improve ASD symptoms. Through these studies, some of the recent dopamine receptors and 3 or 4 of the serotonin receptors have been gradually narrowed down as major targets.

If you simply think about the multi-target approach, you may think that it is okay to adjust only the receptors that you think are important in the necessary way. By raising the activity that is away, or by lowering the activity that is elevated. However, it is technically very difficult to control this all at once. It's very difficult because they're different receptors, they have different shapes, and you can't activate them all at once. It's a very difficult part, but we're researching to make it possible in Neuroventi.

For a long time, Neuroventi has been conducting research to find substances that are most helpful for treatment and have a profile without side effects. And now we are close to success. There are currently candidates with an Optimal Receptor Profile (optimal receptor profile).

To put it simply, we have developed a single substance that ideally regulates serotonin, the main receptor for improving ASD symptoms, and dopamine, which is important for improving ASD symptoms, and is currently developing it as a treatment. It is expected to start phase 2 clinical trials next year.

Q. Recently, a method to treat neurological diseases with electronic medicine technology is on the rise. What kind of synergistic effects are expected?

It is an area that needs to be studied in the future to see what kind of synergistic effect there will be when electronic medicine technology, pharmacological treatment, and behavioral cognitive treatment are combined, and I think it is very important.

For example, I think you can imagine these things. If electronic medicine technology is applied to electrically regulate nerve activity, metaphorically speaking, it will become a ‘nervous system ready to run’. At this time, if the drug is included together, even if the drug is given at a low concentration, the effect of regulating the activity of the nervous system will be greatly seen.

New Ain and we are currently researching how and when neurotransmitters are actually released and regulated in the brain. It seems that such things can be advanced in the future, leading to the development of such a treatment that has no side effects and has good effects.