Non-Invasive Detection of Brain Cell Death Using Methylation Patterns of Circulating DNA: A Novel Blood Test for Early Detection of Alzheimer’s Disease
Project ID : 47-2020-10832
LifeSciences and BioTechnology
Diagnosis, Alzheimer’s disease, cfDNA, Liquid biopsy,
Current development stage
General list: TRL3 Experimental proof of concept
It is estimated that approximately 44 million people worldwide are living with Alzheimer's disease or a related form of dementia. In 2019, Alzheimer’s and other dementias cost approximately $290 billion in the U.S, with costs expected to rise as high as $1.1 trillion by 2050.
Brain atrophy is a prominent pathological feature of Alzheimer’s disease (AD), caused by neuronal loss and correlating with clinical disease manifestation. There are no circulating biomarkers, however, that accurately identify cell death in the brain. The identification of such biomarkers is a major unmet need that could revolutionize the understanding, diagnosis and monitoring of AD.
It is well established that in many tissues, cell death (via apoptosis or necrosis) leads to the release of short DNA fragments into the blood, termed circulating cell-free DNA (cfDNA). cfDNA fragments are short-lived (estimated half-life <1 hour), making them ideal biomarkers for monitoring dynamic processes. Beyond the patterns of fragment size and exact position, cfDNA contains an important layer of epigenetic information, in the form of tissue-specific methylation patterns.
We propose to take advantage of methylation patterns in cfDNA, in order to develop a highly specific and sensitive assay for detection of brain-derived cfDNA, inferring the rate of neuronal, oligodendrocyte and astrocyte cell death at the time of sampling. We are proposing a revolutionary liquid biopsy technology with unprecedented specificity and sensitivity.
In studies published in recent years, Prof. Dor’s team has reported the principles of their approach and demonstrated the ability to detect tissue-specific cfDNA in the plasma of both healthy and sick patients. Employing this approach to identify a novel type of biomarker may transform research and diagnosis of AD.
VP Business Development Healthcare
HUJI, School of Medicine - IMRIC
Developmental Biology and Cancer Research