Erui Xinyue Develops China's First Non-Invasive Blood Test for Parkinson’s Disease Based on Exosome Targeted Enrichment Platform

“It’s as if there’s an eraser in my mind. No one can be happy forever, and my memories are fading away bit by bit.” This iconic line from the 2004 hit Korean drama “A Moment to Remember” marked the moment when Ma Yongxiang, Founder and Chairman of Beijing ERXY Technology Co., Ltd. (hereinafter referred to as “ERXY”), first learned about Alzheimer’s disease, a neurodegenerative disorder.

Ma Yongxiang, Founder & Chairman of ERXY

“The female protagonist in the drama was diagnosed with early-stage Alzheimer’s disease (AD) at the young age of 29, requiring constant, meticulous care from her family. This situation made me deeply worried about whether I, my family members, or my friends and relatives might also develop this disease,” said Ma Yongxiang. Subsequently, Ma Yongxiang consulted numerous experts in hopes of finding a method for precise detection in the early stages of the disease. However, to her dismay, “there were no diagnostic tools available on the market at that time specifically for neurodegenerative diseases such as Alzheimer’s disease.”

However, Ma Yongxiang did not abandon his exploration of this field. A few years later, he made the decisive move to leave QIAGEN, the German multinational corporation where he had worked for ten years, and co-founded ERXY in 2021 with co-founder Li Jia. The company is dedicated to achieving early diagnosis and precision medicine for neurodegenerative diseases and other conditions through exosome technology.

Data from sources such as the China Development Report 2020: Trends and Policies of Population Aging in China, the National Bureau of Statistics, and The Lancet Public Health indicate that by 2019, the number of people with Alzheimer’s disease (AD) in China exceeded 10 million, and is projected to reach 40 million by 2050. Currently, there are over 3 million patients with Parkinson’s disease (PD) in China, a figure expected to rise to 5 million by 2030. As population aging intensifies, neurodegenerative diseases such as PD and AD are characterized by high prevalence rates, an accelerating increase in patient numbers, and a trend toward younger onset ages.

“The growing prevalence of this neurodegenerative disease signals a substantial unmet clinical need,” observed Ma Yongxiang, who has spent many years overseeing regional sales for multinational corporations. This forward-looking perspective is also evident in her previous professional achievements. During her tenure at QIAGEN in Germany, Ma managed sales across multiple regions, delivering consecutive annual sales growth of 40% in her assigned territories. She spearheaded the application of pyrosequencing technology for methylation detection, with related work incorporated into clinical guidelines for glioma. Her team was also among the first in China to develop reagents for CYP2C19 gene polymorphism testing. Furthermore, as an advocate for the concept and practice of clinical biobanking in China, Ma assisted a top-tier neurological specialty hospital in establishing its clinical biobank and helped formulate standards for clinical biobanks.

After leaving QIAGEN, Ma Yongxiang and his friend of ten years, Li Jia, began to assemble their core team. Li Jia graduated with a clinical medicine degree from Peking Union Medical College. He previously conducted gene therapy research in the laboratory of Academician Liu Depei at the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. He then spent 13 years working in tertiary hospitals, holding various positions including at the Molecular Medicine Center of Fuwai Hospital, where he participated in screening for cardiovascular and cerebrovascular risk factors. Leveraging his extensive clinical experience, Li Jia later joined the marketing department of Danaher’s Leica Biosystems, a multinational corporation, where he developed multiple end-to-end solutions that met customer needs.

From clinical practice to the market, the two founders are well aware that enterprises need multidisciplinary talent capable of balancing clinical and commercial demands. In Ma Yongxiang’s view, “building a startup team requires not only selecting partners and experts with experience in clinical and market domains, but also considering team compatibility.”

According to reports, the current core team of ERXY includes several key technical professionals with experience in multinational corporations. These include Dr. Pang Xiaojing, Director of Reagent R&D, who has spent many years exploring neurodegenerative diseases and has published over 20 core papers in internationally renowned journals; Yan Shuming, Director of Equipment R&D, who founded Beijing Houai Medical and developed multiple products that filled domestic gaps; Dr. Yu Jin, Director of Business Development, who previously served as Senior Manager of Strategy and Innovation for Leica Biosystems China under Danaher Healthcare Group; and Dr. Wu Jun, Director of Marketing & Strategic Projects, who formerly served as Product Manager for Digital Pathology at Leica Biosystems.

In 1983, at McGill University in Montreal, Quebec, Canada, Professor Rose M. Johnstone’s research group discovered exosomes in the supernatant of cultured sheep reticulocytes, where they were initially regarded as mere waste products of cellular metabolism. With continuous exploration and discoveries in the field of biology, exosomes have demonstrated broad application potential in areas such as drug delivery, liquid biopsy, tumor therapy, and medical aesthetics.

Exosomes, secreted by living cells and carrying a variety of components such as DNA, RNA, and proteins, are widely present in bodily fluids including blood, urine, ascites, and pleural effusion, and can be stably preserved under low-temperature conditions. Therefore, exosomes have become the “third pillar” in the field of liquid biopsy, following circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs). According to incomplete statistics, there are more than 40 innovative companies worldwide focused on exosome-based therapies and diagnostics, yet very few have launched mature exosome-based liquid biopsy products.

One of the challenges in exosome-based liquid biopsy lies in targeted enrichment. It is reported that most existing exosome enrichment technologies can only extract and purify total exosomes, making it difficult to specifically perform secondary enrichment and targeted capture of exosomes derived from specific cells or tissues. “This results in an inability to accurately reflect the disease status of specific organs.”

To address this issue,ERXY has developed exosome targeted enrichment technology and created the world’s first automated exosome targeted enrichment platform, for which multiple domestic and international patents have been filed.ERXY achieves standardization of the enrichment process through automated equipment, thereby avoiding deviations caused by manual operations and improving the reproducibility of exosome enrichment. “The automated equipment for mass production will feature high integration, compact size, and high throughput. It can not only be applied to clinical testing but also serve as a powerful research tool in the field of life sciences, supporting scientific research scenarios and facilitating clinical translation to unlock greater clinical application value,” introduced Ma Yongxiang.

Based on this technological pathway, ERXY has developedExosome Targeted Enrichment Platform, enabling the purification of exosomes from specific sources in clinical samples. This platform is compatible with various detection methods, including chemiluminescence, ELISA, and single-molecule detection, facilitating clinical diagnostics and scientific research for a wide range of diseases.

The second key aspect of applying exosomes in liquid biopsy lies in the discovery of exosomal biomarkers. Most resource-constrained startups struggle to obtain sufficient clinical samples for the exploration and validation of exosome-related biomarkers, which further complicates the development of exosome-based in vitro diagnostic products.

In 2012, Professor Goetzl and colleagues at the UCSF Medical Center, University of California, published a paper reporting on the enrichment of neuron-derived exosomes, thereby initiating research into the association between their biomarkers and Alzheimer’s disease (AD). In 2020, Jia Jianping’s team at Xuanwu Hospital confirmed through clinical studies that changes in AD pathology-related biomarkers in neuron-derived exosomes were consistent with those of corresponding biomarkers in cerebrospinal fluid. “This demonstrates that blood-based neuronal exosomes can serve as an alternative to cerebrospinal fluid for the detection of AD.”

In the clinical application of neurodegenerative diseases, there are two relatively mature detection technologies: neuroimaging examinations and cerebrospinal fluid biomarker testing. However, both techniques have certain limitations when it comes to large-scale screening. Neuroimaging is relatively expensive, while cerebrospinal fluid sampling requires lumbar puncture, which is somewhat invasive.

“Therefore, to halt or delay disease progression, more accessible and cost-effective methods are needed for the early diagnosis of neurodegenerative diseases. ‘Replacing lumbar puncture cerebrospinal fluid testing with blood-based exosome detection can significantly improve technical accessibility and patient compliance, while also enriching the range of diagnostic markers to create auxiliary diagnostic panels. By developing proprietary technologies to reduce costs, we can offer a comprehensive solution,’ said Ma Yongxiang.”

According to reports, ERXY has established multiple diagnostic product pipelines. Its total exosome extraction kit and neuronal exosome extraction kit obtained regulatory approval and were launched in 2022. Currently, ERXY has completed the development of China’s first non-invasive blood test for Parkinson’s disease (PD), which has passed the Beijing Municipal Innovative Medical Device Review and is currently undergoing registrational clinical trials.

"The PD-assisted diagnostic kit is an in vitro diagnostic product developed using α-synuclein from blood-derived neuronal exosomes as a biomarker, capable of assisting physicians in diagnosing patients with early-stage Parkinson's disease."In our completed pilot study, the sensitivity and specificity for early-stage PD (Hoehn and Yahr stage ≤2.5) both exceeded 80%. Furthermore, we unexpectedly found that this assay kit also demonstrated certain performance in detecting patients with idiopathic REM sleep behavior disorder, with both sensitivity and specificity reaching over 70%."Introduction to Ma Yongxiang"

In addition to its non-invasive blood test for PD, ERXY is also advancing the R&D of fully automated exosome target enrichment devices, as well as ancillary diagnostic products for AD, MCI, and other diseases.

“Currently, there is virtually no early screening or diagnosis for neurodegenerative diseases; by the time a diagnosis is made, the condition has typically progressed to the middle or late stages, significantly reducing the effectiveness of interventions. On the other hand, we urgently need to reframe the perception of neurodegenerative diseases, using early diagnosis to combat the stigma associated with terms like ‘senile dementia.’ This approach will enable clinicians to intervene earlier in disease progression, develop clinical management plans, and implement comprehensive patient care throughout the entire disease course, thereby halting or slowing disease progression,” said Ma Yongxiang.