Exosome research: from platelet dust to pioneering therapeutics

Janet Sasso , Information Scientist, CAS

Exosome CAS Insights article 3

Exosomes are a nanosized subset of extracellular vesicles released from cells as part of their normal physiology or under certain pathologies that are enclosed by a lipid bilayer membrane. First discovered as “platelet dust” in human plasma, they have since been shown to be secreted by most eukaryotic cells, participating in a wide range of physiological and pathological processes.

In previous blogs, we uncovered an overview of the exosome landscape and introduced the ways in which exosomes can potentially be utilized in drug delivery and diagnostics. For the final part of our three-part blog series, we will highlight the breadth of exosome research that is underway in these areas, examining the key developments and future perspectives in this dynamic area.

The key players in therapeutic exosome research

The number of companies that are utilizing exosomes for therapy is rapidly expanding, with both pre-clinical and clinical companies progressing exosome therapeutics through their pipelines. Using data from the CAS Content Collection™, the largest human-curated collection of published scientific knowledge, we explored the targeted diseases that these therapeutic companies are focusing on. We found that the most highly represented targeted diseases in exosome research are cancer, neurological and neurodegenerative diseases, lung diseases, and wound healing, indicating a large amount of candidate exosome products in these areas (Figure 1). While most exosome research platform companies have portfolios that cover multiple therapeutic areas (e.g. VivaZome, Avalon Globocare, and Vitti Labs), some companies tend to specialize in a particular area, such as Kimera Labs and its focus on skin regeneration and wound healing.

CAS Exosome 3 graphic
Figure 1. Promising therapeutic exosome research companies and targeted diseases. 

An appraisal of companies who are investing in preclinical exosome research shows that the US is leading the way, with a diverse pipeline of therapeutic exosomal products. California-based biotech company Capricor Therapeutics is developing multiple exosome platforms including cardiosphere-derived cell exosomes, engineered exosomes, and an exosome-based vaccine for COVID-19. Though their exosome platform is still in the preclinical stages, they have seen promising data in several indications and partnered with other academic institutions to drive their exosome research forward.

Xollent Biotech is another key player in exosome research, with a diversified pipeline of exosome therapeutics. The versatility of exosomes allows for alternative routes of administration, with pipeline treatments comprising of an intravenous patch for treating myocardial infarction, a spray for alopecia, and a needleless injection to combat skin aging. Other companies focusing on cosmetics include Exocel Bio and Florica Therapeutics, which are exploring regenerative stem cell-derived exosome therapeutics in aesthetics and aging.

Diagnostic exosome research: current progress and future directions

As we explored in the previous blog in the series, exosomes have several properties that make them ideal biomarkers, including durability, specificity, and sensitivity. Consequently, the application of exosomes as biomarkers and in diagnostic testing is a growing area of research interest. Though research is still in its infancy, several companies have conducted preclinical exosome research in this area, particularly in cancer. Notable examples include Mercy Bioanalytics and their Halo test for early cancer detection, and research from the University of Texas MD Anderson Cancer Center investigating the use of glypican-1 positive circulating exosomes for detecting early pancreatic cancer.

Organizations are also optimizing diagnostic assays in other therapeutic areas. For example, a collaboration between Harvard Medical School, USA, and Wenzhou Medical University, China, is employing an incorporated Tear-Exosomes Analysis via Rapid-isolation System (iTEARS), which has shown potential in molecular diagnostics of dry eye disease and diabetic retinopathy. Neurodegenerative diseases are also a key focus in exosomal biomarker studies. Researchers at the University of California, San Francisco Medical Center have discovered a panel of biomarkers that could play a role in diagnosing early-onset Alzheimer’s Disease.

Exosome therapeutics in clinical trials

Currently, the total number of clinical trials registered at https://clinicaltrials.gov for exosomal therapeutics is 59 clinical trials. The most highly researched targeted diseases for exosome therapeutics include lung disease (11 clinical trials), SARS-CoV-2 infections (9 clinical trials), along with cancer, heart disease, and neurological diseases (all with 4 clinical trials). Highlighted clinical trials with respect to these diseases are listed in Table 1. For a more comprehensive list of the therapeutics clinical trials, see our recently published Exosome Insight Report.

Table 1. Highlighted exosome therapeutic clinical trials

Company/Medical Centers/Universities (Location) Exosome  Disease treated Clinical Trial Number Clinical Trial Stage or Status (Date initiated)
M.D. Anderson Cancer Center (USA) Mesenchymal Stem Cell (MSC)-derived exosomes with KrasG12D siRNA (iExosomes) Metastatic pancreatic cancer with KrasG12D mutation NCT03608631 Phase I (2018)
Organicell Regenerative Medicine (USA) Amniotic fluid-derived exosomes/Zofin (Organicell Flow) mild/moderate COVID-19  NCT04657406 Expanded Access status available (2020) 
emoveDirect Biologics (USA) Bone marrow MSC-derived exosomes/DB-001/ExoFlo COVID-19 ARDS NCT04657458 Expanded Access status available (2020)
Ruijin Hospital (China) Adipose Mesenchymal Stem Cell-derived exosomes (MSC-Exos) Alzheimer’s Disease induced dementia NCT04388982 Phase I/II (2020)

Exosome diagnostics in clinical trials

Currently, on https://clinicaltrials.gov there is a total of 208 clinical trials with exosomes being used for diagnosis. Over half of these clinical trials (108 clinical trials) are related to cancer diagnosis utilizing exosomes. Other highly represented diseases include neurological diseases (15 clinical trials), cardiovascular diseases (13 clinical trials), and lung diseases (6 clinical trials). Early diagnosis of these diseases is crucial for a better prognosis. The large number of clinical trials of exosomes in diagnosis highlights the value and advantage of using exosomes in early disease diagnosis. Table 2 highlights the companies, medical centers, and universities related to exosome diagnosis of these diseases. For a more comprehensive list of the diagnostics clinical trials, see our recently published Exosome Insight Report.

Table 2. Highlighted exosome diagnostic clinical trials

Companies/Medical Centers/Universities (Location) Exosome (disease target) Disease Diagnosed Clinical Trial Number Clinical Trial Status (Date initiated)
University of Alabama at Birmingham (USA) Blood or Urine-derived exosomes (LRRK2) Parkinson’s disease NCT04350177 Completed (2013)
Boston University (USA) Plasma-derived exosome (tau) Chronic traumatic encephalopathy (CTE) NCT02798185 Active (2016)
Exosome Diagnostics (USA) Urine-derived exosome (ERG, PCA3 and SPDEF) Prostate cancer NCT02702856 Completed (2016)
Lithuanian University of Health Sciences (Lithuania) Eosinophil-derived exosome Asthma NCT04542902 Recruiting (2020)

Exosomes as the disease target in clinical trials

Using exosomes as targets is another avenue that is being explored for disease treatment. Aetholon Medical is a California-based clinical company that has designed an investigational medical device called the Hemopurifier. Targeting circulating exosomes, the Hemopurifier captures viral, bacterial toxin, and cancer exosomes to treat disease. To date, Aetholon has used the Hemopurifer to treat patients with Ebola, hepatitis C, HIV, and COVID-19. Their two current clinical trials are explored in Table 3.

Table 3. Highlighted clinical trials that target exosomes (physical elimination) for disease treatment

Company (Location) Exosome Disease treated Clinical Trial Number Clinical Trial Status (Date initiated)
Aethlon Medical (PA, USA) Circulating exosomes COVID-19 NCT04595903 Recruiting (2021)
Aethlon Medical (PA, USA) Circulating exosomes Squamous Cell Carcinoma of the Head and Neck NCT04453046 Recruiting (2020)

Overcoming outstanding challenges in exosome research

Exosomes are an exciting area of research and present enormous potential for both diagnostic and therapeutic use. However, the clinical applications of exosomes, although highly promising, are currently hindered by gaps in knowledge. Therefore, future work must focus on prioritizing the exact mechanisms of exosome biogenesis and uptake, along with elucidating their interactions with target cells, which together will help researchers advance their therapeutic potential. Another key hurdle to overcome in exosome research is the current challenges with exosome isolation, with a lack of standardization of these processes delaying clinical utility. Finally, the breadth of exosome applications in the pipeline will mean specific regulatory classification and jurisdiction issues need to be clarified to enable development plans to be established.

While significant knowledge gaps must be dealt with, exosome research presents significant opportunities in treating a plethora of diseases – we’ve come a long way from platelet dust.

To learn more, see our recently published Exosome Insight Report.