PLEASANT GROVE, Utah, Aug 8: Renew Biotechnologies 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 signatures in blood across Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.
The findings support a non-protein class of blood biomarkers capable of providing cell-of-origin insight into neurodegeneration. 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.
“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. “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.”
The publication describes 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, PD, ALS, and healthy controls. Across 137 blood samples, the proof-of-concept study identified disease-associated cfDNA signatures corresponding to selectively vulnerable neuronal populations, including 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 values exceeding 0.85.
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.
The findings support the continued development of NeuroLens®, Renew Biotechnologies’ 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 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.
“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. “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.”