Tackling Alzheimer's Research: Bridging the Gap in Preclinical Models
Alzheimer's disease (AD) continues to be one of the most significant health crises facing millions of people worldwide. With over 5.8 million Americans affected, and this number expected to rise dramatically, finding a cure or effective treatment is more urgent than ever. However, the current challenge isn’t just about discovering new drugs—it’s about how to test them effectively.
For researchers, one of the biggest hurdles is the lack of preclinical models that accurately mimic the human brain's complexities, making it difficult to screen potential drugs in a realistic environment.
The Challenge: Inadequate Models Slowing Down Progress
One of the major pain points in Alzheimer's research is the over-reliance on traditional two-dimensional (2D) models using animal cells. While 2D models have advanced our understanding of AD, they fall short in replicating the intricate, three-dimensional (3D) environment of the human brain. This discrepancy often leads to failures in clinical trials, where drugs that performed well in 2D models fail to show efficacy in human patients. Researchers need a model that can more accurately simulate how Alzheimer's impacts neurons, particularly how the brain's response to injury, genetics, and neuroinflammation contributes to disease progression.
This is where new technological advancements, like 3D microfluidic platforms, come into play. These platforms can better mimic the human brain’s complex environment, offering a more relevant model for understanding Alzheimer’s disease.
Why a Better Model is Critical for Alzheimer's Research
Alzheimer's is a multifaceted disease, with numerous contributing factors, including genetics, lifestyle, and even traumatic brain injuries (TBIs). Each factor can lead to the formation of hallmark pathologies like amyloid plaques and neurofibrillary tangles, which ultimately result in cognitive decline. Unfortunately, many of these mechanisms are still poorly understood, partly because of the limitations of existing models.
A more sophisticated in vitro model would allow researchers to not only study these various contributing factors in greater detail but also to observe how they interact in real time. For example, a 3D model using human-induced pluripotent stem cells (hiPSCs) could better replicate the genetic and physiological aspects of the disease, providing insights that a traditional 2D model simply cannot.
A Game-Changer for Preclinical Drug Screening
The need for an advanced model extends beyond understanding Alzheimer's disease—it's crucial for drug development. Hundreds of clinical trials over the past few decades have failed to produce a viable treatment for Alzheimer’s, largely due to the inadequacy of existing preclinical models. A high-throughput system that allows researchers to quickly test new drugs and understand their effects on neurons in a 3D environment could expedite the drug development process. This would save both time and resources, accelerating the path to a potential cure.
One particularly exciting development is the use of a combined traumatic brain injury (TBI)-AD model. This would enable researchers to study how TBIs, which are known to increase the risk of Alzheimer's, exacerbate the progression of AD. Such a model would be invaluable for screening neuroprotective compounds aimed at preventing or slowing down the disease's progression, especially in individuals with a history of TBIs.
The Solution: A Novel 3D Microfluidic Platform
Comparison of MEAs for 2D and 3D cell cultures. The 2D models lack the structural complexity of in vivo systems, whereas 3D models better replicate the brain's natural environment.
CC: Central Chamber; PC: Peripheral Chamber
BMSEED’s microfluidic chip-based platform represents a significant advancement in Alzheimer’s research. This innovative device offers a 3D cellular environment that can assess neuronal health using electrophysiological measurements, simulating both healthy and injured states. The platform enables the study of critical AD pathologies like amyloid plaques and tau tangles, and it offers insights into how neuronal-glial cross-talk affects disease progression.
With this platform, researchers can:
Study neuronal-glial cross-talk: By simulating interactions between neurons, astrocytes, and microglia, researchers can better understand how neuroinflammation and synaptic health impact Alzheimer's progression.
Simulate brain injuries: The stretchable electrodes allow for the simulation of traumatic brain injuries (TBI), helping researchers study how TBIs contribute to the disease.
Test drug efficacy: With its 3D structure, the platform offers a more accurate representation of how drugs will perform in the human brain.
Incorporating stretchable electrodes, this system uniquely allows researchers to simulate brain injuries in vitro, further deepening our understanding of how TBIs may accelerate Alzheimer's pathology. By using human-derived cells in a more physiologically relevant environment, this platform holds the potential to revolutionize the way we study Alzheimer's and screen potential treatments.
Conclusion
The future of Alzheimer's research hinges on our ability to develop better preclinical models. The current limitations of 2D animal-based models have slowed progress in finding effective treatments, but advanced 3D platforms like BMSEED’s offer a solution. By addressing the need for a more accurate, human-relevant system, we can open new doors in understanding the disease and, most importantly, speed up the discovery of life-saving drugs.
At the end of the day, it's not just about the tools we use—it's about ensuring that these tools help us tackle the real pain points in Alzheimer's research: finding treatments that work.
