In a recent article published in the journal Nature Communications, researchers introduced a novel all-in-one wearable system for evaluating drug efficacy on bulbar muscle function in animal models of amyotrophic lateral sclerosis (ALS). This innovative system provides a non-invasive, wireless platform that enables continuous monitoring of muscle activity during natural feeding behaviors.
A) An illustration of the process for evaluating drug efficacy using a wearable device optimized for animal experiments (left), featuring a kirigami strain-isolation mechanism of the wearable electrode (right). B) Schematic anatomy of the head of a rat, showing the location of muscles playing pivotal roles in swallowing. C) A schematic illustration of the progression of motor neuron denervation associated with the advancement of ALS. D) Exploded views of the integrated wearable system, including two EMG electrodes enhanced by the perforated electrode patch, a zigzag-shaped sandwich interconnector, and a wireless circuit. E) A photograph of the ultrathin wearable system seamlessly mounted on the rat. Scale bar: 10 mm. Image Credit: https://www.nature.com/articles/s41467-024-51300-1
Background
ALS is a progressive neurodegenerative disease that primarily targets motor neurons, leading to muscle weakness and atrophy. The bulbar muscles, crucial for essential functions like swallowing and speaking, are often among the first to be affected. Monitoring the functionality of these muscles is vital for assessing the effectiveness of potential treatments.
Current methods for evaluating muscle activity, such as electromyography (EMG), can be hindered by movement artifacts, particularly in animal models. This study addresses the need for a reliable system that captures high-quality EMG signals while allowing subjects to engage in natural behaviors. The authors underscore the importance of minimizing noise from unintended movements, which can obscure accurate muscle activity signals.
The Current Study
The wearable system developed in this study features two primary electrode patches designed to capture EMG signals from the masseter and digastric muscles of rats. These electrodes are made from a conductive material that ensures efficient signal transmission while remaining flexible and comfortable for the animal.
The electrode design is optimized to align with the direction of muscle fibers, which enhances the accuracy of EMG readings. To enable wireless data transmission, the device integrates a Bluetooth Low Energy (BLE) system on a chip (nRF52832, Nordic Semiconductor).
A key innovation in the system is the Kirigami strain isolation mechanism. This mechanism uses a series of strategically placed incisions to allow the substrate to flex and conform to the rat's skin. This design minimizes motion artifacts by maintaining consistent electrode contact, even during vigorous activities like chewing and swallowing.
The EMG signals captured by the electrodes are processed through a custom-designed circuit, which includes an analog front end for signal amplification and filtering. After processing, the EMG data was wirelessly transmitted to a mobile device via BLE.
The study utilized male SOD G93A rats, a well-established model for ALS research. At 20 weeks of age, an osmotic pump containing either Edaravone or a vehicle solution was surgically implanted subcutaneously in the rats. During feeding sessions, the EMG signals from the masseter and digastric muscles were recorded, providing valuable insights into muscle activity and function.
Results and Discussion
The results demonstrated that the wearable system effectively captured high-quality EMG signals from the bulbar muscles of ALS rats, even during natural feeding behaviors. The Kirigami strain isolation mechanism proved successful in maintaining electrode contact and significantly reducing motion artifacts, a common issue with traditional EMG setups.
Continuous monitoring revealed a decline in muscle activity over time, which correlated with the progression of ALS in the animal model. Histological analysis of neuromuscular junctions (NMJs) supported these findings, showing a lower proportion of denervated NMJs in the Edaravone-treated group. This suggests that Edaravone not only preserved muscle activity but also contributed to maintaining NMJ integrity, a critical factor for muscle function.
The device was able to detect both complete and partial denervation, offering valuable insights into the disease's progression and the efficacy of potential treatments. These findings indicate that the system can effectively track ALS progression and evaluate treatment efficacy in a more humane and efficient manner.
By enabling non-invasive, real-time monitoring of muscle function, the device facilitates more accurate assessments of drug efficacy. This approach not only enhances data reliability but also reduces the number of animals needed for testing, aligning with ethical considerations in research. The study underscores the importance of developing technologies that accommodate the natural behaviors of animal models, thereby improving the translational potential of preclinical studies.
Conclusion
In conclusion, the study represents a major advancement in ALS research with the introduction of a wearable system designed for continuous, non-invasive monitoring of bulbar muscle function. The innovative design, which includes a Kirigami strain isolation mechanism and a robust interconnector, effectively overcomes challenges associated with traditional EMG methods, notably improving signal quality and reliability.
The authors expect that this technology will significantly enhance preclinical studies, leading to the development of more effective ALS therapies and deepening our understanding of muscle function in neurodegenerative diseases.
Journal Reference
Shin B., Kwon Y., et al. (2024). All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models. Nature Communications 15, 6803. DOI: 10.1038/s41467-024-51300-1, https://www.nature.com/articles/s41467-024-51300-1