Transforming Technologies into Treatments at the 3rd Annual Neuroscience Day

Mass General Neuroscience, part of Massachusetts General Hospital, recently held the 3^rd Annual Neuroscience Day. Experts from the Departments of Neurology, Neurosurgery, Psychiatry and Anesthesia, Critical Care and Pain Medicine gathered to present on their advances in neuroscience and medical breakthroughs.

Developing Neurotechnologies to Understand the Human Brain

The co-directors of Mass General Neuroscience, William Curry, MD, Joshua Roffman, MD and Jonathan Rosand, MD invited John Ngai, PhD, the National Institutes of Health’s (NIH) inaugural director of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which is a program that aims to revolutionize the understanding of the brain and its disorders.

During his virtual keynote address, Dr. Ngai focused on the creation of technologies to push the boundaries of neuroscience research. He noted that the initial NIH investment to the BRAIN Initiative was $46 million during its first year in 2013, and that it has greatly expanded to nearly $500 million, a third of the way toward the $5.2 billion projected through 2026. Of the nearly 600 awards that have been awarded across the United States, 18 of the BRAIN Initiative awards have been granted to research projects at Mass General.

“It's the time to consider launching some large projects that could potentially transform the way we conduct neuroscience research and apply that knowledge toward human neuroscience,” noted Dr. Ngai, as he outlined the next phase of the BRAIN Initiative, which he referred to as the “brain 2.0 transformative projects.”

One such project is the Brain Initiative Cell Census Network (BICCN), which aims to develop a comprehensive mouse brain cell atlas of cell types by 2021. The data and technology created with the BICCN will be used to catalogue cellular types in the human brain; in turn, this will be used to diagram neural-circuits  and their activity -- all with the ultimate goal of advancing human neuroscience and human neurological disease treatments. 

In developing new technologies, the BRAIN Initiative will aid in the dissemination and democratization of newly developed technologies and data resources. Dr. Ngai highlighted projects funded by the BRAIN Initiative that showcase such technological breakthroughs. Examples included the development of a machine-brain interface that can translate speech from brain activity and creation of a sensory motor neural prosthesis that helps Parkinson’s disease patients regain motor control.

Neuroscience Panelists Discuss Transformative Technologies

Susan A. Slaugenhaupt, PhD, scientific director of the Mass General Research Institute, moderated the Neuroscience Day panel discussion: High Risk, High Reward: Neuroscience and the Pursuit of Transformative Advances in Medicine.

In introducing the panelists, Dr. Slaugenhaupt noted the strength of neuroscience at Mass General, “Neuroscience research at Mass General brings in over $300 million in funding every year. And it takes place across 14 different departments at the institution. The Mass General Research Institute is built on a culture of excellence, compassion and groundbreaking scientific achievement. And our panel today certainly demonstrates those qualities.”

The panel included Brian Edlow, MD, and Sonia Vallabh, PhD, of the Department of Neurology, Mark Richardson, MD, PhD from the Department of Neurosurgery, Emery N. Brown, MD, PhD, from the Anesthesia, Critical Care & Pain Medicine and Jodi Gilman, PhD, of the Department of Psychiatry. 

Dr. Edlow, associate director of the Center for Neurotechnology and Neurorecovery, studies brain networks in comatose patients. He told the story of a young patient who was hit by a car. Before coming to see Dr. Edlow, this patient's parents were told that he would likely die or end up in a vegetative state. However, the patient made a full recovery. The brain imaging technology at the time was incapable of providing detailed information about the injury to the brain tracts suffered by Dr. Edlow’s patient. Now Dr. Edlow advances these technologies to study conscious arousal.

Dr. Edlow summarized the type of research conducted in his lab: “My lab at Mass General focuses on mapping the brainstem arousal network in patients with traumatic coma to identify preserved connections that could support this recovery. We use imaging techniques that map the three-dimensional connectivity of brain networks that are essential for consciousness.”

Dr. Vallabh shared her remarkable quest for a disease-modifying therapy for genetic prion disease, which causes an aggressive neurodegenerative disease. Her mother died of prion disease and Dr. Vallabh herself inherited the causal variant of the gene.

“This makes me nearly certain to die the same way unless we develop a treatment in my lifetime.This was motivating,” said Dr. Vallabh.

She has worked in creating a therapeutic to reduce the fatal prion protein in animal models of the disease and a human version of the drug is in development. However, her vision is much larger.

“We've also learned that we can't predict age of onset in this disease. It appears to strike randomly at some point in adulthood... we want to treat preventively [by] engaging with patients, physicians, regulators, payers, but my hope is if we get this right, we'll be providing an example of what genetically informed primary prevention of brain disease can look like,” said Dr. Vallabh.

Dr. Richardson, director of the Functional Neurosurgery Center, is a neurosurgeon and neuroscientist who treats patients with movement disorders, obsessive compulsive disorder and epilepsy using electrode implantation into the brain. He noted that the advancement of technology will drive treatment of these disorders. 

“Use of a patient's own brain signals eventually will confer the ability to outdo what medications alone can accomplish for many of these brain diseases by orders of magnitude,” said Dr. Richardson. “We have an ambitious goal of creating a real-time, AI-guided platform; personalized therapy for each patient.”

Dr. Brown, director of the Neuroscience Statistic Research Lab, studies the effects of general anesthesia using mathematical modeling, brain imaging and neurophysiology. 

“General anesthesia is about turning the brain off and turning it back on. If we can learn to precisely control how, and by how much we turn the brain off and on in physiological principled ways, we can revolutionize anesthesia care and treat certain neuropsychiatric disorders,” said Dr. Brown.

During his presentation, Dr. Brown outlined the many ways that his research could lend insight into sleep disorders, epilepsy, depression and the aging brain.

He noted, “anesthesiology and neuroscience open an untrodden pathway for using discoveries and innovation from molecular neuroscience and behavioral neuroscience to devise new paradigms for clinical care.”

Dr. Gilman, director of neuroscience in the Center for Addiction Medicine, uses neuroimaging and behavioral testing in humans to understand how drugs and alcohol affect the brain. She spoke to the recent policy shifts across the United States towards legalization and commercialization of both medical and recreational cannabis. She is currently conducting a National Institute on Drug Abuse - funded clinical trial on medical cannabis disorders, including depression, anxiety, pain and insomnia.

“I'm also looking at cannabis use disorder and addiction to cannabis, cognitive changes and brain-based changes,” said Dr. Gilman. “Cannabis is the only example that I can think of where we've basically voted it into existence instead of tested it.” 

The neuroscience research conveying the development of new technologies speak to the incredible research conducted at Mass General. In line with the Brain Initiative, Mass General Neuroscience is part of a critical movement in the development of neurotechnologies that push the boundaries of our understanding of the brain in health and in brain diseases. These presentations represent some of the many projects that will seed the future in combining technology to drive new therapies, a crucial goal of the NIH Brain Initiative.