Neurological Disease ex vivo service
서비스를 소개합니다
AnaBios의 Neurological Disease Assay 서비스는 인간 조직 기반 플랫폼을 활용하여 통증 관련 기능성 분석 서비스를 제공합니다. 이 서비스는 인간 후근신경절(DRG) 뉴런을 사용하여 통증 기전에 대한 약물의 효과를 평가하며, 전기생리학적 (electrophysiology) 분석과 칼슘 이미징 (calcium imaging)을 통해 신경 활성화와 이온 채널 반응을 정확히 측정합니다. 이를 통해 전임상 단계에서 약물의 신경학적 효과를 검증하고 신약 개발의 효율성을 높입니다.
주요 특징
- 전문적인
전기생리학 및 칼슘 이미징 분석:
- DRG 뉴런에서 약물의 작용 메커니즘을 평가하기 위한 수동 패치 클램프 (manual patch clamp)
- 칼슘 이미징
및 전기장 자극을 결합하여 뉴런 흥분성 및 칼슘 변화를 정밀하게 측정
- 인간
조직 기반 데이터:
- 인간 DRG 뉴런 및 조직 샘플을 사용하여 약물의 작용과 독성을 직접 평가
- 동물 모델과
비교해 높은 번역 가능성 제공
- 통증
관련 연구:
- 만성 통증, 신경병증성 통증, 당뇨병성 신경병증 등 다양한 통증 모델에서
약물 효능 평가.
- 나트륨
채널(NaV1.7, NaV1.8 등)에 대한 작용
메커니즘 분석.
- 다양한
분석 가능:
- 나트륨/칼륨 채널 활성, 휴지막 전위, 역치(rheobase), 활동전위 특성 등
- 약물 농도별로 활동전위 발화 빈도와 칼슘 신호를 정량화
이런 서비스 유형을 제공합니다
ACTION POTENTIAL FIRING | VOLTAGE-GATED SODIUM OR POTASSIUM CHANNELS | ||
서비스 유형 | CURRENT CLAMP ASSAY | RAMP CURRENT CLAMP ASSAY | VOLTAGE CURRENT CLAMP ASSAY |
Assay Format | Lead Candidate | Lead Candidate | Lead Candidate |
Prostanglandin E2 + Bradykinin | Prostanglandin E2 + Bradykinin | ||
Oxaliplain | Oxaliplain | ||
Frequency | 0.1, 1, 3, 10Hz | - | - |
농도 개수 | 3 | 3 | 3 |
+ hammer concentration | |||
Number of Cells | 10 | 10 | 5 |
결과 데이터 | Analysis includes rheobase, resting membrane potential, capacitance and number of action potentials at each frequency at each compound concentration. | Analysis includes rheobase, resting membrane potential, capacitance and number of action potentials for each applied ramp at each compound concentration. | |
서비스 장소 | USA |
데이터 자료를 살펴보세요
Figure 1. Carbamazepine Block of action
potential firing. Figure 1 plots the number of
evoked action potentials at the pacing frequencies of 0.1Hz, 1Hz, 3Hz and 10Hz
in 10 neurons that were exposed to two sodium channel antagonists,
carbamazepine and PF-05089771. Error bars are SEM. At 0.1Hz, the neurons are
stimulated by a train of 10 current pulses. At 1Hz, 3Hz and 10Hz, the neurons
are stimulated by a train of 120 current pulses at the respective frequencies.
Both Carbamazepine and PF-05089771 inhibited action potentials in a
concentration and frequency-dependent manner.
Figure 2. Inhibition of TTX-R Currents
in Human Dorsal Root Ganglion Neurons by Known Nav1.8 Blockers. In Figure 2 (above), human donor DRGs were procured using AnaBios’
proprietary surgical techniques and shipped in a proprietary neuroplegic
solution to AnaBios via dedicated couriers. The DRGs were then dissected in
cold neuroplegic solution to remove all connective tissue and fat. The ganglia
were enzymatically digested, and the isolated neurons put in culture.
Cells were plated on coated PDL-coated
coverslips and recordings were made over the first 8 days-in-vitro. Currents
were recorded with an Axon Instruments 700A amplifier and Clampex acquisition
software. Signals were filtered at 3 kHz and sampled at 10 kHz. Currents were
leak-subtracted using a P/-4 protocol. Sodium currents were elicited with a 50
ms voltage pulse to the peak of the I-V curve from a holding potential of
-80mV. Inter-stimulus interval was 10 seconds.
Internal recording solution contained (in
mM): CsF (135), MgCl2 (1), Na-ATP (2), EGTA (1), HEPES (10). External recording
solution contained (in mM): NaCl (20), Choline-Cl (95), KCl (3), MgCl2 (1),
CaCl2 (2), CdCl2 (0.1), NiCl2 (0.1), glucose (25), HEPES (10), TEA (20), TTX
(0.0005). Both test agents were dissolved in DMSO (final DMSO concentration
0.1%).
Figure 3. Schematic of Calcium
Transients Recording in Human Dorsal Root Ganglia neuron. In Figure 3 (above) is a
schematic figure of the recording of calcium transients (calcium steps) in a
human DRG neuron loaded with Fluo-8 and stimulated by electrical field
stimulation. The neural excitability in the form of evoked calcium steps can be
measured simultaneously. The effect of a compound inhibitor can be measured by
comparing the number of calcium steps pre and post addition of the
inhibitor A.
Figure 4. activation of calcium
transients
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