Renew Biotechnologies Publishes Proof-of-Concept Study on Neuron-Derived cfDNA Methylation Signatures for Alzheimer's, Parkinson's, and ALS
核心洞察
Renew Biotechnologies (搜索) published peer-reviewed research in Frontiers in Neurology demonstrating that native DNA methylation analysis of cell-free DNA in blood can identify neuron-associated signatures across Alzheimer's disease (搜索), Parkinson's disease (搜索), and ALS.
The proof-of-concept study across 137 blood samples identified disease-associated cfDNA signatures corresponding to selectively vulnerable neuronal populations, achieving AUC values exceeding 0.85 in multivariate discrimination models.
The approach uses nanopore sequencing to preserve native DNA, eliminating bisulfite conversion and PCR amplification biases while enabling genome-wide methylation profiling from the same dataset.
Renew Biotechnologies (搜索) today announced the publication of its peer-reviewed research in Frontiers in Neurology, providing evidence that native DNA methylation analysis can identify neuron-associated cell-free DNA (cfDNA) signatures in blood across Alzheimer's disease (搜索) (AD), Parkinson's disease (搜索) (PD), and amyotrophic lateral sclerosis (搜索) (ALS). The findings support a non-protein class of blood biomarkers capable of delivering cell-of-origin insight into neurodegeneration — a capability that current blood-based tests largely lack.
"Blood-based biomarkers have transformed the field of neurodegenerative disease, but many currently available tests provide limited information about where neurodegeneration is occurring within the brain," said Chad Pollard, Chief Executive Officer and Co-Founder of Renew Biotechnologies (搜索). "Our goal is to develop biomarkers that not only detect neurodegeneration, but also provide greater biological context by identifying the neuronal populations likely contributing to those signals and how quickly those populations are dying."
A Methylation-Based Cell-of-Origin Approach
When neurons undergo cell death, they release fragments of DNA into the bloodstream. Using native sequencing and methylation-based tissue-of-origin analysis, the study demonstrates how these circulating DNA fragments can be associated with specific neuronal cell types. Unlike current blood biomarkers, which primarily reflect disease-specific protein pathology or generalized neuronal injury, this approach has the potential to reveal cellular origin.
The publication describes three foundational components: the development of a primary human brain methylation reference atlas spanning multiple neuronal and glial cell types, the training of cell-type-associated methylation classifiers, and their application to plasma samples from individuals with AD, mild cognitive impairment (搜索) (MCI), PD, ALS, and healthy controls.
Proof-of-Concept Results Across Three Neurodegenerative Diseases
Across 137 blood samples, the proof-of-concept study identified disease-associated cfDNA signatures corresponding to selectively vulnerable neuronal populations. These included cortical neurons in AD, dopaminergic neurons in PD, and spinal motor neurons in ALS. Multivariate models integrating these neuronal signatures achieved disease discrimination with area under the curve (AUC) values exceeding 0.85, indicating strong discriminatory performance.
The research highlights the advantages of nanopore sequencing for cfDNA methylation analysis. By preserving native DNA, the workflow eliminates biases associated with bisulfite conversion and PCR amplification, and enables genome-wide methylation profiling and sequence analysis from the same dataset. This creates a flexible platform that can expand as additional brain cell reference profiles become available.
Advancing the NeuroLens (搜索)® Platform
The findings support the continued development of NeuroLens (搜索)®, Renew Biotechnologies (搜索)' blood-based cfDNA methylation platform. Since the completion of the study, Renew has processed more than 2,000 patient-derived samples to further develop and validate the technology. NeuroLens® is currently available as a Research Use Only (RUO) product for biomarker and translational research. Renew plans to continue performing validation studies in collaboration with clinicians and research organizations as it prepares to offer the assay as a Laboratory Developed Test (LDT).
"Native cfDNA methylation sequencing opens the door to a fundamentally different way of studying neurodegeneration," said Tim Jenkins, Vice President of Research & Discovery and Co-Founder of Renew Biotechnologies (搜索). "By combining brain cell-type-specific methylation biology with native sequencing, we believe this approach can complement existing blood biomarkers by providing greater insight into the biological processes underlying neurodegeneration."
The full publication, "Circulating neuron-derived cfDNA for blood-based detection of Alzheimer's and other neurodegenerative conditions," is available in Frontiers in Neurology.