New PET radiotracer reveals epigenetic activity of human brain

A novel PET radiotracer developed at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) is able for the first time to reveal epigenetic activity.


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Scientists have devised a new PET radiotracer to reveal the epigenetic activity of human brain. It is the method to discover whether the genes are express in the human brain or not. This is for the first time, scientists are able to design the epigenetics of the human brain. The research was done by scientists from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH).

The packaging of DNA is the key epigenetic mechanism. It wraps around histone protein to form chromatin structure. Alteration of this protein through epigenetic factor could regulate whether an adjacent gene is express or not. Acetyl molecule is one most important factor while addition. Its addition enables gene to translate and removal of deacetylation that prevents transcription.

Jacob Hooker, said, “PET radiotracer a way to start understanding interactions between genes and the environment. It allows us to investigate questions like why some people genetically predispose to disease are protects from it? Why events during early life and adolescence have such a lasting impact on brain health? Is it possible to ‘reset’ gene expression in the human brain?” (Hooker is an associate professor of Radiology at Harvard Medical School.)

One group of HDACs has been linked to important brain disorders. Histone deacetylases (HDAC) are important regulators of gene translation.

The PET radiotracer scans with Martinostat of the brains. Martinostat was designed to tightly bind to HDAC molecules in the brain. The experiment was tested on 8 healthy human volunteers. They then unveiled uptake pattern characteristic by reflecting HDAC expression levels. That expression level was constant from all participants. HDAC expression was almost twice as high in gray matter as in white matter; and within gray matter structures, uptake was highest in the hippocampus and amygdala and lowest in the putamen and cerebellum. Experiments with brain tissues from humans and baboons confirm Martinostat’s binding to HDAC, and studies with neural progenitor stem cells reveal specific genes regulate by this group of HDACs. Many of these are known to be important in brain health and disease.

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Hooker said, “HDAC dysregulation has implicated in a growing number of brain diseases. Thus, being able to study HDAC regulation both in the normal brain and through the progression of the disease. This may help us better understand disease processes. We’ve now started studies of patients with several neurologic or psychiatric disorders. I believe Martinostat will help us to understand different ways these conditions are manifested and provide new insights into potential therapies.”


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