Unleashing the Power of Exosomes for Early Disease Detection

By Paul R. Billings, M.D., Ph.D., CEO at Biological Dynamics, Inc.

In today’s symptom-driven healthcare system, early stage disease can be difficult to diagnose as symptoms often do not appear until the disease has progressed, limiting treatment options. Additionally, there is a lack of effective diagnostic tools that can identify diseases in their nascent stages.

To address the crucial need for early disease detection, researchers are focused on developing novel tools, biomarker approaches, and clinical pathways that more easily and efficiently unlock the power of exosomes to shed light on a broad spectrum of challenging diseases. Until now, the potential of exosomes has remained untapped because current enrichment methods are time-consuming, produce variable results, and require significant manpower. 

Exosomes: An Emerging Biomarker Tool 

Prompted by the need for a more robust diagnostic alternative in cancer, researchers are turning to exosomes. This shift is due to the limitations of the more commonly known biomarker, circulating tumor DNA (ctDNA), which is greatly affected by tumor growth rate and cell turnover rates.

Imagine the inner workings of the body as a superhighway. Traveling on this highway are tiny particles known as exosomes, which can be thought of as delivery trucks carrying vital health information between organs. Exosomes provide many advantages as a biomarker because they are ubiquitous, can be identified in different biological fluids, and can be measured at any time. 

Traditionally, the exosome enrichment process occurs through ultracentrifugation, which can be an arduous, labor-intensive, multi-day process. The challenges in recovering exosomes stem from their small size and low buoyant density. However, researchers recently demonstrated how advanced automated technology using Alternating Current Electrokinetics (ACE) can isolate and characterize exosomes in hours versus days, requiring minimal labor. This lab-on-a-chip technology leverages the semiconductor industry’s expertise and equipment by incorporating silicon wafer substrates and microelectromechanical systems (MEMS chips). By taking advantage of this existing infrastructure and experience, this technology can achieve robust and reproducible laboratory diagnostic results using micron-scale chips that offer favorable economies of scale more typically associated with computer chip production. This is a significant advancement to current methods, which have been a barrier to progress in the clinic. 

Now armed with the ability to capture exosomes using a commercially available proprietary ACE microarray chip system, ExoVerita™ Pro, researchers can significantly reduce the processing steps and time required to isolate and recover exosomes from plasma samples. This breakthrough liquid biopsy technology makes exosome information more accessible for early disease detection and many diagnostic purposes. 

Applications of Exosome Technology in Research

Exosomes have many clinical applications, including as early indicators of health conditions like cancer or neurodegenerative diseases. 

One example is a recent progressive pilot study that demonstrated the promising use of exosomes in the early detection of pancreatic cancer. Often referred to as a “silent killer,” pancreatic cancer is typically discovered in about 80% of patients in its late stages, by which time it has spread and surgery is no longer viable. Unfortunately, nearly all of these patients do not survive beyond five years following their diagnosis. In contrast, early disease diagnosis through vigilant surveillance significantly improves outcomes, with the 5-year survival rate jumping to at least 70%.

The pilot study focused on developing a blood-based biomarker classifier using circulating EVs, including exosomes, for the early detection of pancreatic cancer. The ACE technology platform used in the study allowed for more efficient exosome isolation from a blood sample, leading to a stage I pancreatic cancer detection rate of 95.5%, with a recent study expanding upon these findings. 

As a follow-up, a 2023 case report demonstrated the effectiveness of a liquid biopsy assay powered by the ACE technology in detecting exosome protein biomarkers indicating early-stage pancreatic ductal adenocarcinoma (PDAC) in a 60-year-old patient who presented with pancreatitis. The current standard of care for such patients is a “watch-and-wait” approach that includes frequent scans. The ability to detect cancer earlier using this new generation of biomarkers and technology could bring hope to patients with high-risk factors. 

Adjusting to Evolving Lab Models

A combination of market and regulatory forces creates headwinds to innovation in the American lab-based business model. Complex reimbursement processes often lead labs to offer tests without receiving payment from patients’ insurance providers, resulting in net losses for the labs despite providing critical information needed to manage patient care. Costly treatment plans and lengthy clinic or hospital stays also significantly impact the financial health of patients and their families. Individuals living with cancer, for example, have 61% higher annual out-of-pocket medical expenses than those without the disease. 

Early disease detection can play a role in lowering both patient and treatment center costs by enabling shorter treatment courses, subsequently reducing financial burdens. One study estimated the national cost savings from early diagnosis in the United States to be $26 billion annually. 

Given ACE technology’s user-friendly nature, it is an ideal candidate for laboratory distribution, offering an accessible and cost-efficient option for blood-based liquid biopsy tests, pending regulatory approval. This advancement could pave the path toward a portable diagnostic prototype, signaling a positive shift toward more patient-centered care. Mobile diagnostic options incorporating exosome isolation capabilities hold immense potential for the early detection of challenging diseases and allow for timely interventions when symptoms are either not present or just beginning.

Expanding Diagnostic Capabilities with Exosomes & AI

Current health guidelines recommend screenings for a limited number of diseases, mainly for those with risk factors such as age and family history. Historically, these individuals have been challenging to identify because of incomplete or inaccurate medical records and unknown family medical histories. However, when exosome screening methods pair with emerging technologies like artificial intelligence (AI), we can cast a wider net and increase the number of candidates enrolled in surveillance programs. Once identified, advanced diagnostic assays can be used for monitoring, leading to timely interventions and more targeted care. 

Integrating exosomes and other cutting-edge technology offers a new approach to early disease detection and advanced diagnostics. Streamlining and improving the isolation process makes vital information more accessible to researchers and eliminates the challenges associated with exosome enrichment. Through continued research, innovation, and strategic adjustments to existing lab models, we are charting a course toward a healthier and more cost-effective future in medicine. This breakthrough holds immense promise, offering a paradigm shift toward proactive and personalized patient care. 

About the Author

Paul R. Billings, MD, Ph.D., FACP, FACMGG, is CEO and Director of Biological Dynamics, Inc. He is devoted to studying and teaching medicine and genetics while accelerating the use of a broad range of novel genomic technologies in clinical settings. Over his decades in healthcare, he has established key business partnerships, driving the adoption of innovative discoveries and commercial success. Dr. Billings has held academic appointments at Harvard University, U.C. San Francisco, Stanford University, and U.C. Berkeley; and served as a board-certified internist and medical geneticist.

He published doctoral studies at Harvard, supervised by Dr. Baruj Benacerraf, who subsequently received the Nobel Prize in Medicine. He has served on the Scientific Advisory Board of the FDA, the Genomic Medicine Advisory Committee at the Department of Veterans Affairs, and as an appointee to the Secretary’s Advisory Committee on Genetics, Health, and Society at the Department of Health and Human Services. He has been Chief Medical Officer or Senior Physician at Laboratory Corporation of America Holdings, Life Technologies Corp, Thermo Fisher Scientific Inc., and Natera, Inc. He holds an M.D. and a Ph.D. in Immunology from Harvard, where he won the Shipley Prize for best-published research results, and an Artium Baccalaureus, summa cum laude, from U.C. San Diego.