Devastating brain diseases like Frontotemporal Dementia and Alzheimer’s have been painfully slow to give up their secrets. But behavioral neurologist Brad Dickerson, MD, and his Mass General research team are tracking an important protein that has long eluded measurement in the living brain. Their work may mark a turning point in how such now-incurable conditions are understood and treated.
When it turns toxic, tau is a known culprit in a cascade of biological events that kill brain cells.
The researchers are using ultra high-resolution imaging techniques to measure signals and abnormalities related to a protein called tau. When it turns toxic, tau is a known culprit in a cascade of biological events that kill brain cells. Until recently, tau was only visible under the microscope after death. “We can now see tau in a living brain and measure it,” says Dr. Dickerson, director of Mass General’s Frontotemporal Disorders (FTD) Unit. “We’re closer than ever before to pinpointing exactly what’s going wrong in the brain of a person with dementia early in the illness, which is the foundation we need to develop targeted treatments.”
Dr. Dickerson describes tau as being like railroad tracks that need to stay straight to transport nutrients and other “supplies” within the brain. When tau starts to have problems, he says, “it essentially rusts, twists and tangles, clogging up the machinery of brain cells so they eventually die.”
Tracking Brain Disease Progression
Dr. Dickerson has a background in biomedical engineering. At the MGH Martinos Center for Biomedical Imaging, he is using brain scans and other techniques to quantify the differences between normal and abnormal aging in the brain. These measurements can help diagnose and monitor the progression of brain disease. They may also be used to test new treatments.
Because such disorders are relatively uncommon, many neurologists and psychiatrists may only see one person with FTD in their entire careers. Since Dr. Dickerson founded the FTD Unit eight years ago, he and the multidisciplinary team have cared for about 400 people with FTD and their families.
Dr. Dickerson can often tell just by interacting with someone whether he or she is at the beginning of FTD or not. That diagnostic skill is then backed by the tests his team has devised to more precisely identify and quantify the severity of FTD.
The neurologist says he is inspired by Katie Brandt and others whose loved ones suffer through these cruel, dementia-related diseases of the brain. “FTD robs people of their core essence, the personality that makes us who we are, very early in the disease,“ Dr. Dickerson explains.
Personalizing Stem Cells
In the past, hopes about exciting treatments have been repeatedly dashed when something that worked in a mouse model didn’t help people. Working together, the Mass General laboratories of Dr. Dickerson and Stephen Haggarty, PhD, are pursuing a new strategy. There, researchers are exploring the use of personalized stem cells to better model the human brain and test potential new treatments.
Treatments they are investigating include new drugs and ways to stimulate the brain with electrical, magnetic or light energy.
“Now we have this amazing technology that allows us to take a little sample of skin from a person’s arm and reprogram the skin cells into stem cells that have that person’s own genetic make-up,” Dr. Dickerson explains. They then turn the stem cells into brain cells. These cells actually start making connections with each other in a petri dish, simulating what happens in the brain.
Treatments they are investigating include new drugs and ways to stimulate the brain with electrical, magnetic or light energy. Through collaborations with Mass General experts in genetics, molecular biology and pathology, “we are trying to come up with new ideas like these that we can try in people for the first time,” he says.
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