Introduction
This episode of Translating Aging, hosted by Chris Patil from BioAge Labs, features Dr. Alex Aravanis, CEO and co-founder of Moonwalk Biosciences. Dr. Aravanis, who has an extensive background with companies like Illumina and Grail, discusses the promising new frontiers of precision epigenetic medicine. The conversation focuses on Moonwalk's mission to leverage epigenetics to develop novel therapies, potentially extending human healthspan and tackling complex diseases.
Key Takeaways
- Dr. Alex Aravanis and his team at Moonwalk are exploring the potential of precision epigenetic medicine to develop novel treatments for complex diseases.
- The approach centers around modifying epigenetic states to restore or improve cellular functions, offering an alternative to traditional gene or small molecule therapies.
- The technology's ability to read and "write" the epigenome opens up numerous possibilities for disease treatment, especially in cardiometabolic health and other complex disease areas.
Key Points
Dr. Alex Aravanis' Journey and Collaboration with Feng Zhang
Dr. Aravanis recounts his early career path, including his time at Stanford, where he obtained an MD-PhD in electrical engineering, blending medicine and engineering in an unusual but highly effective combination. During his postdoc, he collaborated with Carl Diceroth and Feng Zhang, leading to the pioneering of optogenetics—a technique that has revolutionized neuroscience. This laid the groundwork for his ongoing collaboration with Feng Zhang and eventually co-founding Moonwalk Biosciences.
Dr. Aravanis explains that his engineering mindset—focusing on building tools to truly understand systems—helped him approach the challenges in biology and medicine differently. His roles at Illumina and Grail further shaped his expertise, particularly in early cancer detection and leveraging advanced sequencing technologies for clinical medicine. His collaboration with Feng Zhang has endured over time, forming the basis for Moonwalk's current ventures.
Moonwalk's Core Mission and Approach to Epigenetics
The central mission of Moonwalk Biosciences is to harness the power of the epigenome—the "source code" that regulates DNA expression across different cell types. Unlike traditional therapies that focus on genetic mutations or small molecules, Moonwalk aims to directly modify epigenetic markers to restore the desired functions within cells. This targeted approach could lead to more precise and durable therapeutic outcomes compared to conventional methods.
Moonwalk’s technology allows them to "read" the epigenetic landscape, identifying changes related to disease states, and "write" or modify specific epigenetic markers. By directly altering methylation patterns or histone states, Moonwalk can influence gene expression to treat diseases. This epigenetic modification is also surprisingly durable, inheriting through cell divisions and maintaining the changes without constant intervention.
Applications in Cardiometabolic Diseases
One of Moonwalk's first targets is cardiometabolic health, including conditions such as obesity and fatty liver disease. Dr. Aravanis discusses the exciting potential of modifying adipocytes—particularly in transforming white fat cells into metabolically active brown-like cells. Brown fat cells, known for their role in thermogenesis and energy dissipation, could provide a new pathway for combating metabolic diseases without relying solely on calorie restriction.
The company is also interested in the broader application of energy balance regulation as a therapeutic tool, looking to enhance metabolism in ways that mimic the natural, higher metabolic activity seen in youth. This approach seeks to address patients who cannot tolerate current GLP-1 agonists or other weight loss drugs due to side effects like muscle wasting or gastrointestinal issues.
Precision and Safety of Epigenetic Modification
Dr. Aravanis emphasizes the safety and precision of Moonwalk’s epigenetic modifications compared to traditional gene-editing tools like CRISPR. Instead of inserting or deleting genetic material—which can lead to off-target effects—Moonwalk modifies the chemical state of DNA, such as methylation, with high specificity. The durability of these modifications is particularly beneficial for clinical applications, as the changes persist across cell divisions without the need for ongoing treatments.
He acknowledges the potential risks, such as unintentionally activating oncogenes, but reassures that the flexibility in design and empirical testing reduces the risk of such off-target effects. This cautious approach aims to balance innovation with safety, ensuring that the technologies developed are both effective and reliable for clinical use.
Comparing Moonwalk to Other Epigenetic Reprogramming Efforts
During the episode, Dr. Aravanis contrasts Moonwalk's approach with that of other leading biotech companies exploring epigenetic reprogramming, such as Altos Labs and RetroBio. While these companies often use Yamanaka factors for partial cellular reprogramming to rejuvenate cells, Moonwalk focuses on making direct epigenetic changes. The difference lies in the fact that Moonwalk is not seeking to dedifferentiate cells back to a stem-like state but rather aims to optimize their existing functional state by modifying specific epigenetic markers.
This distinction allows Moonwalk to mitigate some of the risks associated with over-reprogramming, such as the development of teratomas, while still providing therapeutic benefits that enhance cell function and health. The company is charting a path that focuses on incremental, controlled changes rather than sweeping cellular reprogramming.
Future Directions for Moonwalk Biosciences
Looking ahead, Dr. Aravanis outlines Moonwalk’s priorities for the next few years, which include advancing their target pipeline through animal studies and moving toward clinical trials. They are also focusing on leveraging AI models to better predict the effects of epigenetic modifications on gene expression and cellular behavior. This AI-driven approach aims to enhance both target discovery and the development of precision therapies.
The goal is to create predictive models that incorporate the complex relationships within the epigenome to expedite drug discovery and make Moonwalk’s platform more versatile and powerful. They also plan to pursue partnerships to expand their impact, particularly in disease areas where Moonwalk’s resources alone may be insufficient.
Conclusion
The overall takeaway from this episode is that Moonwalk Biosciences is pioneering a novel approach to treating complex diseases by directly targeting the epigenome. This method holds the promise of offering precise, durable, and safe modifications to gene expression, potentially addressing diseases that are difficult to treat with existing therapies. Dr. Aravanis and his team aim to transform our understanding of what’s possible in drug discovery and human health by unlocking the full potential of the epigenetic landscape.
Moonwalk's work represents a significant step forward in precision medicine, focusing on reprogramming cellular behavior without the broad risks associated with more radical approaches. Their exploration of cardiometabolic health and their dedication to epigenetic research could have profound implications for the future of aging and metabolic disease treatment, ultimately contributing to healthier, longer lives.