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Neurological Disease 서비스

AnaBios는 Drug Discovery의 모든 단계에 Human Tissue Sample 및 Service를 제공합니다.

INTRODUCTION

 

96%

모든 동물실험 화합물의 96%가 임상시험에서 실패합니다.

동물과 인간사이의 생화학적 및 생리학적 차이는 전임상 단계에서의 안정성 및 효능연구를 임상결과로 전환하는데 있어 가장 큰 장애 요인입니다. 동물 모델은 생물의학연구 및 약물 발견에 필수적인 도구이지만 동물 실험 화합물의 96%가 임상시험에서 실패한다는 사실은 전임상 단계에서 human Data 추가의 필요성을 보여줍니다.

AnaBios의 advanced human tissue-based methods은 동물 모델을 인간의 체외 연구에 통합하는 현대화된 접근 방식을 가능하게 하며, in vivo (in animals)의 이점과 ex vivo (Human data)의 데이터를 통해 종간 번역 문제를 극복할 수 있는 전략을 제공합니다.

Advantage of human-focused drug discovery

  • 병든 조직에서 약물 표적을 정확하게 식별가능
  • 동물 모델의 translatability을 보정
  • 실제 인간 표적을 사용하여 lead compounds의 효능과 안전성을 극대화 가능
  • 동물 모델의 잘못된 양성 및 잘못된 음성 독성 신호를 극복 가능
  • 서로 다른 모델 종에서 발생하는 불일치 결과를 해결
  • 검증된 인적 데이터로 IND 애플리케이션을 개선
  • 임상 연구를 위한 dose selection 가이드

Pain relate assay 

ico_chk01 Viable hDRG (Human Dorsal Root Ganglia Neurons) for drug screening

ico_chk01 Electrophysiology-based studies in human DRG neurons (Whole Cell Patch Clamp Electrophysiology)

ico_chk01 Calcium Imaging in hDRG neurons

Capsaicin-induced response in hDRG neuron

Multi-parametric testing of large neuronal populations

  • ATP, capsaicin, menthol, AITC, mechanoreceptors, low pH, etc.
  • In vitro inflammation model (Bradykinin)
  • Electrical-field stimulation
  • Acute and chronic effects

ico_chk01 Human DRG action potential firing (Electrophysiology – current clamp)

  • Rheobase
  • Drug inhibition of action potentials as a function of concentration and firing frequency
Number of Drug Concentrations Frequency (Hz) Number of Cells per Concentrations

Comments

Screening 1 10 3 This assay is a strong predictor of human analgesic critical information on use-dependence, activity in pathological states, human dosing
Lead selection 3 0.1, 1, 3, 10 5
Inflammation

(PGE2/Bradykinin)

3 0.1, 1, 3, 10 5

 

ico_chk01 Drug selectivity (Calcium Imaging with Electrical Field Stimulation)

Drug selectivity for specific neuronal subpopulations

  • Cells expressing TTX-S vs. TTX-R
  • A delta-like vs. C-like neurons
  • Cold- vs. heat-sensing neurons
Number of Drug Concentrations Drug Incubation time (min) EFS

Frequency (Hz)

Voltage Intensity Number of Cells per Concentrations Comments
Screening 1 5 5 Low 25 This assay is very helpful in identifying drug target neuronal population and most appropriate pain indication
Lead selection 3 5 to 15 5, 20 Low, High 25
Inflammation

(PGE2/Bradykinin)

3 5 to 15 5 Low, High 25
Inflammation ((PGE2/Bradykinin) 3 5 to 15 Spontaneous activity NA 25
Neuropathy (oxaliplatin) 3 5 to 15 5 Low, High 25

 

ico_chk01 Drug selectivity (Calcium Imaging)

Drug selectivity for specific neuronal subpopulations

  • TRPV1
  • TRPA1
  • TRPM8
  • ASIC/TRPV1
  • P2X
  • Opioid receptors
Number of Drug Concentrations Drug Incubation time (min) Number of Agonist (s) Number of Cells per Concentrations Comments
Screening 1 5 1 25 This assay is very helpful in identifying drug target neuronal population and most appropriate pain indication
Lead selection 3 5 to 15 Up to 3 25
Inflammation

(PGE2/Bradykinin)

3 5 to 15 1 25
Neuropathy (oxaliplatin) 3 5 to 15 1 25

 

ico_chk01 IC50 determination (Electrophysiology – voltage clamp)

  • Nav (total)
  • Nav 1.7
  • Nav 1.8
  • TRPV1
  • TRPA1
  • Kv
  • Cav
Number of Drug Concentrations Drug Incubation time (min) Number of Cells per Concentrations Comments
Screening 1 5 3 Potency estimate derived from IC50 measurement is a less reliable predictor than inhibitor of action potential
Lead selection 3 5 5

 

ico_chk01 Itch (Assays in isolated adult hDRG neurons)

  • Histamine
  • Chloroquine
  • Bam8-22
Number of Drug Concentrations Drug Incubation time (min) Number of Agonist (s) Number of Cells per Concentrations Comments
Screening 1 5 1 25 This assay is very helpful in identifying drugs with potential anti- Itch effect in human
Lead selection 3 5 to 15 Up to 2 25
Inflammation

(PGE2/Bradykinin)

3 5 to 15 1 25

 

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