A Novel Human 3D Neuromuscular Junction Model for Drug Discovery
A New Approach to Potency and Safety Testing with Scalable Creation and Easily Quantifiable Results
Histological Characterization of NMJs
The Future of Neuromuscular Junction Modeling
Preclinical models, including animal models and traditional 2D/3D setups, often fail to accurately predict drug performance in human clinical trials. This is due to a lack of physiological relevance, low throughput, and challenges in quantitating results.
A Breakthrough in 3D NMJ Models
Curi Bio has designed, built, and validated a functional human 3D model of the neuromuscular junction (NMJ) using the Mantarray platform. This innovative model provides several key advantages:
Optogenetic Control: It uses blue light to specifically activate motor neurons, allowing for independent study of both neural and muscle function.
High-Throughput & Reliability: The model has a high success rate of NMJ creation (>95%) and uses an automated, cloud-enabled software for data analysis, making it ideal for preclinical efficacy and safety testing.
Physiologically Relevant: The model uses iPSC-derived motor neurons and skeletal muscle to more accurately mimic human physiology.
Diverse Applications: It enables the study of motor neuron diseases, neurotoxin effects, and other synaptic mechanisms.
Speak with Curi Bio’s Services Team to Get Started
Validated Performance: A Proof of Concept
Functionality was validated through several key findings:
Histological Evidence
Curi Bio has histological proof of NMJs, which is essential for many disease modeling applications.
Functional Characterization
Co-cultures exhibited elevated spontaneous contractions compared to single-cultured skeletal muscle tissues. When activated with blue light pulses, the skeletal muscle in the co-culture showed synchronized contractions within 100 milliseconds of the applied light pulses.
Botulinum Toxin Blockade
Curi Bio demonstrated a dose-dependent loss of NMJ function in the presence of Botulinum toxin (BoT). The tissues showed sensitivity to BoT synapse blockade, with function reduced to 0.03% after four hours of treatment with 5 µg/mL of BoT. This effect was specific to the neuronal component, as the skeletal muscle itself remained functionally competent. Curi Bio also generated a dose-response curve, determining an EC50 value of 0.114 µg after 24 hours of exposure.
Preclinical Testing and Potency Assays
This platform serves as a powerful new tool for preclinical drug discovery and a potential solution for potency testing of biological products such as Botulinum neurotoxins.
The Mantarray Platform Enables:
Easy, rapid casting.
Over 95% casting success rate.
Label-free tracking of 24 tissues.
Well-based electrical stimulation of 24 tissues.
Automated metric extraction.
Clinically relevant protocols.
With the Mantarray platform, you can bypass the limitations of traditional models and get more accurate, reliable results.
Learn More About Curi Bio’s Neuromuscular Junction Model
Conduct faster, more predictive potency assays with Curi Bio’s NMJ model.
If you are interested in learning more about how Curi Bio’s NMJ model can accelerate your research, please contact us to arrange a conversation with our team of experts.
More Neuromuscular Junction Resources
Read Publications
The Future of Neuromuscular Junction Modeling
Preclinical models often fail to predict how compounds will perform in human clinical trials, leading to a high rate of failure. Current animal models often don't accurately reflect human physiology and screening more than a handful of drugs is not a realistic workflow and is cost prohibitive.
Previous 2D and 3D models of the neuromuscular junction (NMJ) have also fallen short, lacking the reliability, simplicity of engineering, and high-throughput capabilities needed for effective testing. Furthermore, there has not been a straightforward method for quantitation/interpretation of in vitro NMJ activity.
A Breakthrough in 3D NMJ Models
The Curi Bio team has designed, built, and validated a functional human 3D model of the neuromuscular junction using our established Mantarray 3D engineered tissue platform. This model utilizes optogenetics to drive motor neuron firing (and resultant muscle contraction) while also allowing direct stimulation the muscle. This provides a number of key features and unique advantages:
In-situ neurosphere creation, which eliminates the need for direct spheroid handling.
Blue light sensitive neurons that allow for specific activation of motor neurons independently of the skeletal muscle.
iPSC derived motor neurons and skeletal muscle.
High success rate of NMJ creation (>95%).
Measure motor neuron disease associated function, pre vs. post-synaptic mechanisms, neurotoxin blockade of synaptic transmission, improvements in innervation, etc.
Automated cloud-enabled software for quantitation of function making an ideal model for preclinical efficacy + safety testing or potency assays.