Unveiling Hidden Potential: Organoids for Disease Modeling in Neuroscience Research

insights from industryRosanna ZhangHead of Strategic InitiativesACROBiosystemsIn our latest interview, News-Medical speaks with Rosanna Zhang from ACROBiosystems about utilizing organoids for disease modeling in the field of neuroscience research.

Please can you introduce yourself and tell us a little about your background in neurology?

I’m Rosanna Zhang, and I currently serve as the head of Strategic Initiatives at ACROBiosystems, leading its innovative endeavors across the globe starting from Aneuro and transferring it into our global seed fund, focusing on investment and licensing-in life science tools. I received my undergraduate degree at MIT and conducted research at Harvard, MIT and Mass General Hospital. My research was focused on uncovering the pathology of neurodegenerative disease and finding a stem cell-based therapy for amyotrophic lateral sclerosis.

Can you tell us about Aneuro? What does Aneuro hope to achieve in the field of neuroscience research?

Aneuro is our brand that encompasses all products and reagents for neuroscience research. We started it in 2021 in hopes of providing more ready-to-use tools to accelerate research for neuroscience-related diseases. With new, potential biomarkers being consistently discovered alongside mapping the entire brain neural network, up-to-date tools, and reagents such as recombinant proteins, antibodies, cell lines, and organoids are all critical for performing cutting-edge research. We aim to provide a comprehensive panel of products for neuroscience research and help accelerate the development of novel therapeutic and diagnostic options.

Image Credit: ACROBiosystemsImage Credit: ACROBiosystems

How is Aneuro supporting therapeutic research when it comes to neurodegenerative diseases?

As a scientist, having high-quality life science tools and solutions is essential towards finding meaningful, reproducible data. Especially when combating a disease that has been historically difficult to overcome such as Alzheimer’s, ALS, and many other neurodegenerative diseases, it becomes even more critical to have cutting-edge solutions to keep your research on track. Of course, this applies not only to research but in industry, where emphasis focuses more on more mature, scalable, and reproducible methods.

Aneuro supports both academic and industry applications by offering high-quality solutions that are essential in studying the intricate cellular processes, whether it includes higher-degree, complex disease modeling tools, or electrical probes for in vivo research. These tools collectively aid in deciphering disease mechanisms, identifying potential drug targets, and developing innovative therapies, crucial for combating neurodegenerative disorders, ultimately striving toward improved diagnostics and effective treatments for affected individuals.

What are organoids? How do organoids contribute to advancing neuroscience research, particularly in the context of disease modeling?

Organoids are miniature three-dimensional organ-like structures grown from stem cells that can emulate the complexity of human brain tissue in a lab setting. These self-organizing structures mirror specific aspects of brain development, offering an unprecedented platform to study neurological disorders, synaptic connectivity, and neuronal behavior. Their resemblance to actual brain tissue enables researchers to investigate disease mechanisms, test drug responses, and explore personalized medicine approaches, fostering deeper insights into conditions like Alzheimer's, autism, and other neurodevelopmental disorders. Organoids represent a promising frontier, bridging the gap between traditional cell cultures and human brains, propelling advancements in understanding brain function and disease pathology.

Can you explain the key advantages of using organoids over traditional cell culture models when studying neurological diseases?

Image Credit: nobeastsofierce/Shutterstock.com

Image Credit: nobeastsofierce/Shutterstock.com

Key advantages of using organoids really comes down its ability to mimic the cellular composition of the human brain. It offers a closer representation to the complexity of the human brain, which means that when used for disease modeling, results for organoids are usually more representative towards human brains. This also means the ability to study limited brain functions outside of a living source and uncovering mysteries that cannot be observed otherwise. Of course, this also unlocks the ability for personalized medicine – by using patient-derived cell sources, disease models specific for an individual can be developed. This means personalized treatment plans and a better therapeutic action plan at the individual level rather than population. Finally, organoids also address the ethical concerns regarding animal testing, providing an alternative to the long-standing standard of mouse and other animal testing.

What are the challenges associated with creating and maintaining organoids for disease modeling in neuroscience, and how are researchers addressing these challenges?

As with any more recent advancements, the key challenge associated with organoids is consistency. Reproducibility and standardization of organoid generation has always been difficult due to the variability in cell culture conditions and differentiation protocols available. Results have always been heavily dependent on expertise, not to mention labor-intensive and time-consuming. Generating these organoids at scale is a significant limiting factor that prevents wider adoption in industry. As such, research and commercialization efforts have been heavily dedicated towards improving scalability and refining cell culture methods while addressing the varying ethical concerns regarding developing brain tissue models.

In what ways do organoids accurately recapitulate the complex cellular and structural features of the human brain, making them suitable for disease modeling?

Organoids emulate intricate cellular and structural aspects of the human brain, enhancing their relevance in disease modeling. Their three-dimensional architecture mirrors the organization of brain regions, allowing the development of diverse cell types akin to those found in the brain. They exhibit neural connectivity, synapse formation, and electrical activity resembling the human brain, facilitating the study of neuronal interactions. So not only do organoids have the same hallmark cellular composition of a brain, but they also mimic that intracellular signaling between different cell types that conventional cell lines lack. As such, certain organoids can exhibit limited physiological functionalities under the right conditions, such as electrophysiological activities (e.g. heartbeats) in cardiac organoids. 

This limited functionality also means that disease-specific pathological hallmarks can also be displayed, offering insight into disease progression. Moreover, the incorporation of patient-derived cells allows personalized disease modeling, capturing individual variations in disease presentation and drug responses. While not an exact replica, these characteristics enable organoids to simulate crucial features of the human brain, making them valuable tools for understanding neurological disorders and advancing potential treatments.

Could you provide examples of specific neurological disorders or conditions that have been successfully modeled using organoids, and discuss the insights gained from these studies?

Organoids were first introduced in the early 2000s, with a wide array of research and understanding derived from the use of organoid models. Researchers have used organoids to observe how the Zika virus causes microcephaly during embryo development, which in turn leads to stunted brain development. At the cellular level, viral infection drives the premature differentiation of neuron-producing cells, which is something that can be only observed by utilizing in vitro models. Similarly, other researchers have used organoids to connect disease pathology to a genetic-level insight – comparing organoids derived from autistic patients to a control. Although a main genetic abnormality involved in cell proliferation was identified, its role in autism remains to be uncovered. Despite the lack of conclusion, these hints that are unique to the use of organoids are what makes it so valuable as a tool in a neuroscience researcher’s toolkit.

How do researchers ensure the reproducibility and reliability of results obtained from organoid-based disease models, considering the variability in organoid cultures?

Ensuring reproducibility and reliability of organoids and its results really comes down to experience and the materials that you use. Having consistent, trustworthy reagents is the first step towards reproducible organoid culturing, with your own experience and protocol driving the rest of your research. Having a defined kit and protocol is always a great way to kickstart research in organoids and saves a lot of time in troubleshooting and solving any potential issues that might arise as one gets started in organoids. 

Can you discuss the translational potential of findings from organoid-based disease models and how they might influence the development of new therapeutic interventions?

Image Credit: Gorodenkoff/Shutterstock.com

Image Credit: Gorodenkoff/Shutterstock.com

The translational potential of findings from organoid-based disease models holds significant promise in shaping new therapeutic interventions for various neurological disorders. As mentioned before, these models provide a closer representation of human brain complexity, aiding in the understanding of disease mechanisms and potential treatment strategies. By using organoids derived from patient-specific cells, researchers can replicate individual disease characteristics, allowing for personalized medicine approaches. This personalized modeling helps identify specific drug responses and potential therapeutic targets, thus paving the way for precision medicine in treating neurological conditions.

Additionally, organoid-based disease models enable more efficient drug screening by offering a platform to test potential treatments in a system that closely mimics human brain tissue. This facilitates the identification and validation of novel drugs, potentially speeding up the drug development process.  Furthermore, insights gained from organoid studies regarding disease progression and the underlying cellular and molecular mechanisms provide a deeper understanding of neurological disorders. This knowledge can guide the development of innovative therapeutic interventions, including gene therapies, targeted drug delivery systems, and other precision-based treatments tailored to the specific pathology of each disorder. While challenges exist, such as scalability and standardization, the translational potential of organoid-based disease models remains promising. They offer a bridge between bench research and clinical applications, potentially revolutionizing the development of new therapeutic interventions for neurological disorders.

As organoids continue to evolve as a tool for neuroscience research, what are the most pressing research questions or gaps in knowledge that need to be addressed in the field of organoid-based disease modeling? How is Aneuro accelerating research to answer these questions?

When it comes to neuroscience, the biggest research question is always ‘why.’ Understanding how our brains work and the influencing factors that might cause diseases and abnormalities is always the first step in finding ways to combat neurodegenerative disease and develop effective therapies. With Aneuro, we seek to accelerate research by providing tools that scientists can trust and focus more on contributing to the understanding of neurodegenerative diseases and understanding our brains.

Finally, looking forward, what exciting research developments are you optimistic about, and what is next for Aneuro?

Although this isn’t that much of a research development, I am very optimistic about the adoption and utilization of organoids into a more industry-related context. The potential of organoids has been undeniable in research, and with the increasing availability of consistent organoid kits, organoids, and other life-science tools on the market, it seems likely that therapies combating neurodegenerative diseases is right around the corner.

Where can readers find more information?

About Rosanna Zhang

I currently serve as the Head of Strategic Initiatives at ACROBiosystems, leading its innovative endeavors across the globe starting from Aneuro and transferring it into our global seed fund, focusing on investment and licensing-in lifeRosanna Zhang science tools. I received my undergraduate degree at MIT and conducted research at Harvard, MIT, and Mass General Hospital. My research was focused on attempting to find a stem-cell therapy cure for ALS and uncover the pathology of neurodegenerative diseases. Afterwards, I gravitated towards entrepreneurship and research commercialization, co-founding a healthcare IT start-up company while investing in life-sciences and biotech companies.

Coming to ACROBiosystems, I hope to provide researchers with the best tools, reagents, and equipment required to tackle the unsolved puzzles in life sciences, especially in neurodegenerative diseases. This fight is somewhat personal to me, having an autistic family member. Thus, I want to contribute as much as I can to helping develop therapies against neurological diseases and significantly improve the lives of patients across the world.

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