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
Viable hDRG (Human Dorsal Root Ganglia Neurons) for drug screening
Electrophysiology-based studies in human DRG neurons (Whole Cell Patch Clamp Electrophysiology)
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
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 |
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 |
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 |
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 |
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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