Application:

  • Accurately measuring neuronal cell death from a simple blood draw could transform diagnosis and monitoring of brain injuries, neuro-degeneration and drug neuro-toxicity. 
  • Existing cfDNA assays that rely on brain-specific CpG methylation markers lack the sensitivity and specificity required for clinical use, particularly when neuronal DNA represents only a very small fraction of total circulating DNA.

Our innovation:

  • We have discovered that non-CpG (CpH) methylation (especially at CpA and CpT sites, which occurs in ~10 % of neuronal DNA but is absent from other tissues) provides a uniquely powerful molecular signature. Detecting methylated CpH in cfDNA therefore pinpoints neuron-derived fragments regardless of genomic locus.
  • A purpose-built analysis algorithm further boosts accuracy by discarding reads that show conversion artefacts (methylated CpC) and requiring multiple methylated CpA/CpT sites per read.
  • The method is compatible with shallow next-generation or nanopore sequencing, so only a small amount of DNA is needed.

Advantages:

  • Ultra-high sensitivity – ~15 000 neuron-assigned molecules per M reads vs ~1 per M in leukocyte DNA
  • Extremely low background – healthy plasma shows virtually no neuronal cfDNA, enabling clear detection window
  • >4-order-of-magnitude signal gain over current CpG or limited-marker CpH assay
  • Finger-prick volume sufficient – shallow sequencing of tiny DNA inputs possible
  • Versatile sample types – whole blood, plasma, CSF, saliva, urine, dried blood spots, forensic material
  • Simple workflow – no bisulfite conversion needed when using nanopore sequencing

Opportunity:

We are seeking collaboration with diagnostic-platform companies, sequencing-technology providers, and biotech/pharma firms developing CNS therapeutics. The goal is to co-develop and license assay kits, companion diagnostics, or point-of-care tests that use our neuron-specific CpH-methylation method to detect brain-derived cfDNA for clinical monitoring, drug trials, and emergency triage.

Contact in Yissum: Ariela Markel