The technique could help understand and develop treatments for brain disorders including Alzheimer’s and schizophrenia.
Image: H.-Y. Wey et al., Science Translational Medicine
Advances in imaging techniques are bringing the human brain into closer focus than ever before. Now, researchers have unveiled another "first" in brain imaging: a visualisation of epigenetic activity (the mechanisms that affect gene expression) in a living human brain. This could help show the role epigenetics plays in different disorders, and even help develop drugs to then treat them.
Epigenetics looks at changes in gene expression (i.e. whether a gene is turned "on" or "off"), something that is linked to all kinds of disease, including brain disorders such as Alzheimer's, schizophrenia, and depression.
"There's this fascinating disconnect between the genes you're given through inheritance from your parents and how those interact in your life to lead to all sorts of things, one of which is disease," explained Jacob Hooker, a radiologist at Harvard Medical School and an author on the new imaging study. This can be the difference between someone being affected by or protected from a disease.
Hooker and his coauthors seek to understand more about epigenetics in the brain. "In order to be able to do that, you need a way to be able to monitor epigenetic regulation over the course of someone's life," he said. "You can't just wait until a person dies and take a snapshot of the brain tissue after death to figure out what happened."
In the new study, published Wednesday in the journal Science Translational Medicine, the researchers set out to do this by imaging the density of a type of enzyme called histone deacetylases (HDACs), which are known to regulate gene expression and have been implicated in brain functions.
The challenge is being able to image this in a living brain. To do so, the researchers developed a radioactive imaging agent they called Martinostat, which binds with HDACs to make them visible in a PET (positron emission tomography) scan. Having previously been tested in animals, this is the first time it was used in humans.
In the resulting images, red areas show the highest density of HDACs and blue the lowest.
In the study, the researchers imaged the brains of eight healthy adults for 90 minutes after injecting them with Martinostat. It wasn't without difficulty. "The caveat is that the radioactive drug has a half-life of only 20 minutes, so we actually had to manufacture it on-site for every scan," said Hooker.
He also emphasised the importance of funding, as it took years to learn about the molecules and develop the imaging technique, just as it does to develop a new drug.
Hooker said the images from the healthy brains were not unexpected, though he was a little surprised to see the consistency of HDACs across the brain. "What that may suggest to us is that it's important—that the regulation of histone deacetylases is so important that the brain is regulating it that tightly," he added.
Now, the researchers are turning their attention to brain disorders. Hooker said they had already imaged some people with schizophrenia and Huntington's disease, and just received funding to scan patients with Alzheimer's disease.
They hope their work will help fuel pharmaceutical companies developing epigenetic drugs and also better characterise diseases.