R&D

We promise to open new horizons in the biomedical field..

Research Areas

  • We focus on the development of new drugs for the treatment of intractable neurological diseases through the development of derivatives of FDA-approved non-toxic core molecules. Clinical research has confirmed that these substancesmolecules have excellent therapeutic efficacy against autism spectrum disorder, an unsatisfied demand field.

  • There are no safe therapeutic agents as yet for intractable neurological diseases such as autism spectrum disorder (ASD), Alzheimer's disease (AD), Parkinson's disease (PD) etc., despite the fact that many studies have been conducted in various fields worldwide.

  • We are focusing on developing new drugs for first-in-disease or first-in-class treatment by overcoming the treatment limits of existing intractable neurological diseases that will inflict minimal side effects.

  • Autism Spectrum Disorder
  • Alzheimer’s disease
  • Parkinson‘s disease
  • Cerebral infarction
  • Traumatic Brain Injury
  • Amyotrophic Lateral Sclerosis

Autism Spectrum Disorder (ASD)

What is autism spectrum disorder (ASD)?

ASD is a neurodevelopmental disorder characterized by poor social interactions with others, problems with verbal/non-verbal communication, and repetitive and limited behavior/interest/activity.As of 2018, autism spectrum disorder was present in 1.7% of children, with about 1 in 59 people affected by the disorder. While developmental differences can be found with peers before the age of three, it is sometimes diagnosed only at school age in children with relatively good intelligence or self-care function.

Classification of ASDs

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5), revised in May 2013 by the American Association of Mental Health Medicine, is primarily used to diagnose disorders such as autism. In the 4th revision (DSM-IV TR), the overall developmental disorder was classified into five types (autistic disorder, Asperger's syndrome, nonspecific general developmental disorder, Rett syndrome, and childhood disintegrative disorder). In recent years, this classification has been viewed from a single spectrum perspective, and autism disorders, Asperger's syndrome, and nonspecific general developmental disorders, previously classified as separate disorders, have been combined into a common umbrella term of ASD.

Classification of autism spectrum disorder
Diagnostic criteria (2 areas)
  • Defects in social interaction and communication
  • Limited and repetitive behavior/interest/activity
3 essential symptoms
  • Lack of social interaction
  • Lack of social communication
  • Lack of playmates or friendship
Limited and repetitive behavior / interest / activity (more than 2 out of 4 items)
  • Repetitive physical movements, repeated use of objects or speech
  • Adhering to everyday patterns or ritual activities without flexibility
  • Intensity or concentration limited to an abnormal degree
  • Excessively sensitive or insensitive to pain, temperature, light, sound, or other sensory stimuli, or excessive or insufficient attention
Severity
  • Level 1: Requires help and support
  • Level 2: Requires significant help and support
  • Level 3: Requires considerable help and support
Outcome
  • Meets diagnostic criteria → ASD diagnosis
  • Does not meet criteria → social communication disorder

Causes of autism spectrum disorder

ASD is a brain development or growth disorder, the precise cause of which is still unknown. Currently, it is assumed that various causes such as genetic factors, neuroanatomical and neuropathological factors, biochemical factors, and immunological problems all work in combination. There are reports of high risk of autism-related symptoms in the presence of prenatal, perinatal, and postpartum complications, and these brain development problems indicate a comprehensive anomaly in sociality, language, emotion regulation, and cognition.

ASD statistics

The global prevalence of ASD has rapidly increased with the highest prevalence reported in Hong Kong, Korea, and the United States (Figure 1). About 1% children of the total population in the United States were diagnosed with ASD according to estimates from the CDC report, in 2018.in The incidence of ASD was five times higher in boys than girls. In Korea, the prevalence of ASD in 2011 was 2.6%, which was way-out compared to the 1% prevalence in the US and Europe (Am J Psychiatry. 2011;168:904-912). The number of ASD registered cases in korea is continuously increasing from 13,933 in 2007 (about 9.02%) to 24,698 in 2017 (about 10.94%).

Lives of ASD patients

The symptoms of the disorder appear in early childhood. There is no cure for ASD, and patients have to face difficulties daily throughout their lives. The problems of communication, social interaction, and the sharing of emotions and interests put forth huge challenges. Thus, there is a desperate need for a guardian, but at the same time, it incurs high socio-economic impact.

Alzheimer’s disease (AD)

What is Alzheimer’s disease (AD)?

Dementia is a chronic degenerative brain disease that causes problems such as cognitive decline, and impairment of concentration, thinking, and language skills. It has emerged as a serious social problem in recent years in the aging society. Dementia is classified as Alzheimer's, Vascular, Lewy's, Parkinson's, Frontotemporal and Alcoholic Dementia depending on the cause of the disease. Alzheimer's type of dementia accounts for more than 60-70% cases.

Causes of AD

  • 1) Accumulation of beta amyloid (β-amyloid)

    • Currently, beta amyloid accumulation is known to be the leading cause of AD. When beta-amyloid is excessively produced and accumulated in the brain, senile plaques are formed, which interfere with the synaptic transmission of signals between neurons and consequently destroy the brain cells.
  • 2) Superphosphorylation of Tau protein

    • Tau protein maintains the stability of nerve cells by binding to microtubules and preventing their collapse. When tau protein is separated from the microtubules due to its hyper-phosphorylation, it aggregates inside the cell and forms a neurofibrillary tangle, which interferes with signal transmission.

Dementia statistics

According to the Ministry of Health and Welfare statistics, the number of people with dementia in Korea is expected to double in next 20 years as we enter an aging society. Compared to those in their 60s, dementia is 2-3 times more likely in people in their 70s and about 39 times more likely in people aged over 85.

Economic status of dementia.

The cost of dementia care has increased by 7.3 times in 2017 from 2007, and the socio-economic burden is expected to further rise in the future.

Status of dementia treatment

Treatment of AD is currently limited to acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Acetylcholinesterase inhibitors, like donepezil, rivastigmine, and galantamine are used as treatments for patients with mild to moderate Alzheimer's disease. However, the drugs currently in use are merely symptomatic having little therapeutic effect, and are not applicable for treatment of all AD patients. Thus, fundamental treatments for AD patients are desperately needed.

Parkinson‘s disease (PD)

What is Parkinson’s disease (PD)?

Parkinson's disease (PD) is caused by damage or death of nerve cells, which regulate movement. The three main symptoms of Parkinson's disease are 'bradykinesia' (body movements slow abnormally), 'resting tremor' (hands or feet shake), and 'rigidity', (muscle and joint movements become stiff).

Causes of PD

Dopamine is a neurotransmitter that is involved in muscle activity, and adopaminergic loss of more than 60% causes dyskinesia, a symptom of PD. However, the exact cause of damage and death of the nerve cells that control movement has not yet been determined. PD has some genetic etiology, but environmental factors are significant determinants of the disease.

PD’s statistics

Looking at the distribution of dementia and PD patients in their 40’s and 50’s, patients with PD are about 9 times more prevalent than those with dementia. PD occurs in 1~2 out of 100 people over the age of 65 years.

Economic status of PD

PD’s is accompanied by physical and cognitive impairments, which adds to the economic cost burden. Lack of social and economic support significantly affects the quality of life compared to other degenerative brain diseases.

Status of PD treatment

PD requires medication that takes into account patient's age, condition, and occupation. Drugs currently used for patients with PD are levodopa (a precursor to dopamine) formulation, a dopamine agonist that stimulates the receptor of dopamine, a monoamine oxidase B inhibitor that inhibits dopamine degrading enzymes, and an anticholinergic that helps relieve tremor symptoms including trembling hands and feet. However, these drugs many side effects and can only control the symptoms of PD but cannot cure the disease.

Cerebral infarction (CI, stroke)

What is cerebral infarction (stroke)?

Cerebral infarction is a neurological symptom that occurs when a blood vessel that supplies blood to a part of the brain is blocked or ruptured, causing damage to the brain. Consequently, there are many different symptoms representatives including paralysis or numbness of the face and one limb, pronunciation disorder, speech disorder, gait disorder, consciousness disorder, and dizziness; in particular, in case of brain hemorrhage, sudden nausea, vomiting, and headache are common. It is necessary to avoid cholesterol-rich food, smoking, and excessive alcohol consumption, carry out regular exercise and undertake regular check-ups for diabetes or heart disease.

Causes of cerebral infarction.

Cerebral infarction is a disease in which blood vessels supplying oxygen to the brain become clogged. Few of the several causes including hypertension, diabetes, hyperlipidemia, smoking, excessive alcohol consumption, obesity, and anomalies in blood flow to the brain, can result in brain hemorrhage and cerebral infarction due to lack of adequate blood flow.

Cerebral infarction statistics

Major risk factors of cerebral infarction are aging and increased chronic diseases. According to the acute phase cerebral infarction adequacy evaluation data conducted by the Health Insurance Review and Assessment Service, out of 100 cerebral infarction patients, 76.3% were stroke, 14.5% were intracranial hemorrhage, and 8.9% were subarachnoid hemorrhage. The incidence of cerebral infarction in hypertensive patients is –four to five times higher in the general population and two times higher in diabetic patients. The disease prevalence increased with age, and one in 60 adults is found to suffer from the disease. In addition, according to the analysis of the Korean Stroke Society Epidemiology Research Society, as of 2014, cerebral infarction prevalence was 1.71% in adults over 19 years of age.

Economic status of cerebral infarction.

Cerebral infarction can cause serious aftereffects or death, and is one of the most socially and economically burdensome diseases in Korea, especially in geriatric population. As of 2015, estimated direct cost of cerebral infarction care was about 1.6840 trillion Won. or 64.3 per 100,000 population, This disease is the second leading cause of death after cancer.

Status of cerebral infarction

Cerebral infarction, as a single disease in Korea, has the highest mortality rate. The problem is of sequelae (late effects) of cerebral infraction is as serious as patient death. The disease is accompanied by damage in brain cells. The damage can be irreversible even if blood supply is inadequate for only 2-3 minutes, and as a result, many patients experience speech, motor, and cognitive impairments and have difficulties in daily life. For this reason, it is important to take immediate treatment for the disease within the golden time, but only 4 out of 10 patients (40%) visit within 3 hours (the golden time) of the symptom occurrence.

Traumatic Brain Injury

What is traumatic brain injury?

Traumatic brain injury can be defined as brain damage caused by external influences such as traffic accidents, industrial accidents, sports accidents etc. The incidence rate increases as modern society becomes more complex. The most common cause of traumatic brain injury is traffic accidents, which are mostly obstructive and are accompanied by physical or neurological disorders caused by multiple or local injuries. Traumatic brain injury is the leading cause of death and disability worldwide and ,can be fatal especially in children and adolescents.

Classification

It is clinically classified into four groups of injury levels: mild, moderate, severe, and vegetative states and the characteristics of each group are as follows.

Classification
States
  • Features
Mild (post-concussion syndrome)
  • The most common brain damage
  • Loss of consciousness for a short time
  • No local neurological defects, but minor neuropsychological and behavioral defects
Moderate
  • Intermediate state of mild and severe
  • Patients with initial Glasgow coma scores of 9 to 12 or traumatic memory loss between 1 and 24 hours
Severe
  • Patients recovering consciousness but showing obvious disability
  • At least 6 hours of loss of consciousness
  • 10% of all traumatic brain injury patients
  • Significant recovery can be achieved through active rehabilitation treatment
Vegetative
  • Difficulty recovering consciousness due to severe brain damage
  • Not knowing the surroundings, unable to speak or voluntarily exercise
  • Sleep and arousal, yawning, avoidance responses to pain stimuli, and other lower brain tissue reactions

Causes of traumatic brain injury

Brain injury caused by external impact is mainly caused by coup injury that occurs on the part hitting an object and contrecoup injury that occurs on the other side due to acceleration.

Traumatic brain injury statistics

According to the Center for Disease Control (CDC) report in December 2019, the number of traumatic brain injury patients increased by 1.2 fold in 10 years from 983,976 in 2008 to 1,206,345 in 2017. The major areas where damage occurs are the spine (22.1%), traumatic brain injury (14.6%), and knee and lower limbs (11.1%). The proportion of damage inflicted on the nervous system is relatively high; the incidence rate is higher in men (60.5%) than in women (39.5%) and higher in children aged 0-4 years and adults aged 45-54 years.

Lives of patients with traumatic brain injury

Traumatic brain injury occurs commonly in children or young people with active economic activities. It is not limited to physical pain, but also psychological pain, and physical rehabilitation and various rehabilitation education programs are required. Fortunately, unlike degenerative brain disease, brain's plasticity and resilience is high; therefore, prompt and appropriate first aid immediately after the injury is critical.

Amyotrophic Lateral Sclerosis (ALS)

What is amyotrophic lateral sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a disease that develops as neuromotor neurons degenerate. The disease manifestations include dysarthria, dysphagia and ultimately dysfunction, such as respiratory failure due to the loss of nerve cells in the brain. Consequently, destruction of the nervous system of the brain stem, spinal cord, and veterinary muscle neurons follow.

Classification of ALS

It is a neurological disease that begins with mild muscle weakness and progresses to hand movement and micromotor abnormalities, resulting in weakness of the leg muscles, failure of the voice box function, sudden cramps in the muscles, and accelerated muscle reflexes. Depending on the initial symptoms, ALS can be divided into limb and bulbar types.

근위축성 측삭경화증의 분류
Limb type
  • Motor neuron damage located in the cervical spinal cord
  • Initial symptoms: paralysis of hands and feet
  • About 75% of patients with amyotrophic lateral sclerosis
  • Features of limb thinning due to muscle atrophy of the limbs as problems arise in the use of limbs
Bulbar type
  • Damage to motor neurons located in the brainstem
  • About 25% of amyotrophic lateral sclerosis patients
  • Classified as bulbar
  • As the strength of the tongue, mouth, and neck muscles weakens, the larynx function is lost, and eventually dysphagia, which causes communication problems and difficulty swallowing food

Causes of ALS

Apart from genetic factors (10%), ALS is known to be associated with damage to motor nerves due to lifestyle and exposure to certain toxic substances, such as group outbreaks caused by specific regional or environmental factors.

  • 1. Genetic factors

    It is inherited as an autosomal dominant or recessive trait, and mainly occurs in adulthood in cases of autosomal dominant inheritance and in childhood or adolescence in cases of sex chromosomal recessive inheritance (juvenile onset).
    • ALS1
      • It accounts for approximately 15-20% of hereditary amyotrophic lateral sclerosis cases. The autosomal dominant gene type is caused by mutations in the Cu/Zn-superoxide dismutase (SOD1, 21q22.1) gene.
    • ALS2
      • It is an autosomal recessive genetic trait (2q33), and ALS2 usually appears in the age range of 10-20 years and progresses slowly upto 10-15 years.
    • ALS4
      • It is located on the long arm of chromosome 9 (9q34) and is autosomal dominant, and characteristically occurs in the 20s age group.
  • • In addition, six other genetic mutations have been reported.

  • 2. Sporadic factors

    Like other degenerative brain diseases, the cause of the disease is not clearly known. The following factors are known to be involved from case reports of patients. It is known that two or more factors are involved in combination rather than a single factor that independently causes the disease.
    • Immunological factors
      • Loss of motor neurons by genetic programs of microglial cells and astrocytes
    • Neurotrophic factors
      • Deficiency and blockage of neurotrophic factors
    • Glutamic acid excess
      • The premise that glutamate, an excitatory neurotransmitter, is present at high concentrations at the junction of motor neurons, causing toxic effects on neurons, and destroying motor neurons, and to date, studies are underway on the selective destruction of only nerve cells, among other cells in the nervous system
    • Free radicals and oxidative stress
      • Accumulation of reactive oxygen species (ROS) in vivo causes oxidative stress leading to degradation of enzymatic proteins, and loss of mitochondrial function leading to neuronal cell death. In ALS patients, the association of mutation of superoxide dismutase (SOD), which is involved in the neutralization of the generated ROS, has been reported, but its direct correlation with the actual disease has not been established till date.
    • Other theories include virus infection and heavy metal accumulation due to environmental pollution.

ALS disease statistics.

The global number of ALS patients per 100,000 populations is 2 to 6, and in the United States, there are approximately 30,000 ALS patients in total and hence, ALS is classified as a rare disease. About 5-10% of the patients belong to the familial ALS due to family history, and the incidence is common in men than in women. The onset of the disease is rare before the age of 40, and most often occurs between 40-70 years.