News

Oscine Therapeutics -- a biotechnology company that is developing cell-based therapies for neurological disorders based on discoveries made at the University of Rochester Medical Center (URMC) -- has been acquired by Sana Biotechnology for undisclosed terms.

The research behind Oscine is based on decades of work in the lab of Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience and co-director of the URMC Center for Translational Neuromedicine. Goldman's research has focused on understanding the basic biology and molecular function of the glial support cells in the central nervous system, devising new techniques to precisely manipulate and sort these cells, and studying how cell replacement could impact the course of neurological diseases. Goldman, who was Oscine's president and scientific founder, joins Sana as senior vice-president and head of Central Nervous System Therapy. He will also remain on the URMC faculty.

Sana Biotechnology, which has operations in Washington, Massachusetts, and California, was created in 2018 with a focus on developing and delivering engineered cells as medicines for patients. The company is led by a team of biotechnology industry veterans and supported by more than $700 million in investment. Last year, the company invested in Oscine's R&D in neurological disorders, in what remains the University of Rochester's largest-ever commercial spin-off.

The exclusive licenses for the portfolio of technologies and equity stake that the University of Rochester held with Oscine have been acquired by Sana. The University and Goldman may continue to receive significant licensing, milestone, and royalty payments from Sana going forward.

"The University of Rochester has been working closely with Dr. Goldman's lab and the Oscine team from its inception," said Scott Catlin, director of UR Ventures, the University's technology transfer office. "We are thrilled with the company's impressive progress and its acquisition by Sana and look forward to continue supporting the commercialization of Dr. Goldman's technologies."

Goldman's research focuses on support cells in the brain called glia. In many neurological diseases -- such as multiple sclerosis, Huntington's, and neuropsychiatric disorders -- these cells either disappear or malfunction. This ultimately leads to the motor, cognitive, and behavioral symptoms of these disorders. Goldman's lab has shown that replacing these sick cells with healthy ones can slow and even reverse disease progression in animal models of these diseases.

The Center for Translational Neuromedicine maintains labs in Rochester and at the University of Copenhagen in Denmark. Goldman's research for cell-based therapies has received relevant support from the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Lundbeck Foundation, the Novo Nordisk Foundation, CHDI, and NYSTEM.

Maiken Nedergaard, M.D., D.M.Sc. has been awarded the International Prize for Translational Neuroscience of the Gertrud Reemtsma Foundation for her research in the glymphatic system, the brain's unique waste removal process.

Nedergaard's research was recognized by the Foundation for findings that "offer new approaches for treatments and preventive measures for Alzheimer's and other neurodegenerative diseases."

First discovered by researchers in the URMC Center for Translational Neuromedicine in 2012, the glymphatic system piggybacks on blood vessels and pumps cerebrospinal fluid, washing waste from the brain. The accumulation of toxic proteins like beta amyloid are linked neurological disorders, including Alzheimer's disease. Nedergaard's lab has since gone on to show how sleep disruption, age, and injury can impair the brain's ability to effectively remove waste.

Nedergaard was presented the award at a ceremony at the Max Plank Society in Cologne, Germany on September 10.

New research details how the complex set of molecular and fluid dynamics that comprise the glymphatic system -- the brain's unique process of waste removal -- are synchronized with the master internal clock that regulates the sleep-wake cycle. These findings suggest that people who rely on sleeping during daytime hours are at greater risk for developing neurological disorders.

"These findings show that glymphatic system function is not solely based on sleep or wakefulness, but by the daily rhythms dictated by our biological clock," said neuroscientist Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and senior author of the study, which appears in the journal Nature Communications.

The findings add to a growing understanding of the operation and function of glymphatic system, the brain's self-contained waste removal process which was first discovered in 2012 by researchers in the Nedergaard's lab. The system consists of a network of plumbing that follows the path of blood vessels and pumps cerebrospinal fluid (CSF) through brain tissue, washing away waste. Research a few years later showed that the glymphatic system primarily functions while we sleep.

Since those initial discoveries, Nedergaard's lab and others have shown the role that blood pressure, heart rate, circadian timing, and depth of sleep play in the glymphatic system's function and the chemical signaling that occurs in the brain to turn the system on and off. They have also shown how disrupted sleep or trauma can cause the system to break down and allow toxic proteins to accumulate in the brain, potentially giving rise to a number of neurodegenerative diseases, such as Alzheimer's.

Each of us carts around a 3-lb. universe that orchestrates everything we do: directing our conscious actions of moving, thinking and sensing, while also managing body functions we take for granted, like breathing, keeping our hearts beating and digesting our food. It makes sense that such a bustling world of activity would need rest. Which is what, for decades, doctors thought sleep was all about. Slumber was when all the intricate connections and signals involved in the business of shuttling critical brain chemicals around went off duty, taking time to recharge. We're all familiar with this restorative role of sleep for the brain--pulling an all-nighter or staying awake during a red-eye flight can not only change our mood, but also affect our ability to think clearly until, at some point, it practically shuts down on its own. When we don't get enough sleep, we're simply not ourselves.

Yet exactly what goes on in the sleeping brain has been a biological black box. Do neurons stop functioning altogether, putting up the cellular equivalent of a Do Not Disturb sign? And what if a sleeping brain is not just taking some well-deserved time off but also using the downtime to make sense of the world, by storing away memories and captured emotions? And how, precisely, is it doing that?

A year later, a biological explanation for why poor sleep might be linked to Alzheimer's emerged. Dr. Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester, identified a previously ignored army of cells that is called to duty during sleep in the brains of mice and acts as a massive pump for sloshing fluid into and out of the brain. This plumbing system, which she dubbed the "glymphatic system" (it works in parallel to the lymph system that drains fluid from other tissues in the body), seemed to perform a neural rinsing of the brain, swishing out the toxic proteins generated by active neurons (including those amyloid fragments) and clearing the way for another busy daily cycle of connecting and networking.

Taken together with Holtzman's discovery that levels of amyloid spiked during the day and dropped during sleep, Nedergaard's findings gave further credence to the theory that sleep might perform a housekeeping function critical for warding off diseases like Alzheimer's. "These results very much support the notion that one of the roles of sleep is to actually accelerate the clearance of beta amyloid from the brain," says Nora Volkow, director of the U.S. National Institute on Drug Abuse.

A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function. The study provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

"These findings demonstrate that through the transplantation of human glial cells, we can effectively achieve remyelination in the adult brain, " Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience at the University of Rochester Medical Center (URMC), co-director of the Center for Translational Neuromedicine, and lead author of the study. "These findings have significant therapeutics implications and represent a proof-of-concept for future clinical trials for multiple sclerosis and potential other neurodegenerative diseases."

The findings, which appear in the journal Cell Reports, are the culmination of more than 15 years of research at URMC understanding support cells found in the brain called glia, how the cells develop and function, and their role in neurological disorders.

Goldman's lab has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create glia. A subtype of these, called glial progenitor cells, gives rise to the brain's main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells.

Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine, professor in the Departments of Neurology, Neuroscience and Neurosurgery, received the Thomas Willis Lecture Award from the American Stroke Association. The award honors Nedergaard's career of significant contributions to the basic science of stroke research.

The Nedergaard lab is dedicated to deciphering the role of neuroglia, cell types that constitute half of the entire cell population of the brain and spinal cord.

Last month, the lab published research showing that during a stroke the glymphatic system goes awry, triggers edema and drowns brain cells. In 2012, Nedergaard and her colleagues first described the glymphatic system, a network that piggybacks on the brain's blood circulation system and is comprised of layers of plumbing, with the inner blood vessel encased by a 'tube' that transports cerebrospinal fluid (CSF). The system pumps CSF through brain tissue, primarily while we sleep, washing away toxic proteins and other waste.

The Thomas Willis Award honors the prominent British physician credited with providing the first detailed description of the brain stem, the cerebellum and the ventricles, with extensive hypothesis about the functions of these brain parts. The award recognizes contributions to the investigation and management of stroke basic science.

Nedergaard was one of eleven leading scientists honored for their work by the American Stroke Association. The awards were given during the American Stroke Association's International Stroke Conference in Los Angeles.

Oscine Therapeutics, a new biotechnology company based on discoveries made and developed at the University of Rochester Medical Center (URMC) has received a significant multi-year investment to support both research and development of cell-based therapies for neurological disorders. The funding represents the largest-ever investment in a URMC start-up company.

The new venture is based on decades of research in the lab of Steve Goldman, M.D., Ph.D., co-director of the URMC Center for Translational Neuromedicine. Goldman's work has focused on understanding the basic biology and molecular function of support cells in the central nervous system, devising new techniques to precisely manipulate and sort these cells, and studying how cell replacement could impact the course of neurological diseases.

Goldman has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create the brain's support cells, called glia. A subtype of these, called glial progenitor cells, gives rise to the brain's main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells.

"Neurological disorders are complex diseases, but in many instances it appears that faulty support cells of the brain are driving the disease process," said Goldman, the URMC Distinguished Professor of Neuroscience and Neurology. "These diseases represent promising targets for cell-replacement therapies because we know a great deal about the role these cells play, how to create them, and how to get them to the areas of the brain where they are needed."

The investment in Oscine is being made by Sana Biotechnology, a new company focused on creating and delivering engineered cells as medicines for patients. The company is led by a team of biotechnology industry veterans with extensive experience in cell therapy, gene therapy, and gene editing. The company is backed by visionary investors including Arch Venture Partners, Flagship Pioneering, and F-Prime Capital Partners.

Deep sleep allows the brain to wash away waste and toxic proteins more efficiently, according to a new mouse study published in the journal Science Advances. The new findings shed light on previous evidence linking Alzheimer's disease with aging and sleep deprivation.

"Sleep is critical to the function of the brain's waste removal system and this study shows that the deeper the sleep, the better," said Maiken Nedergaard, MD, DMSc, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.

"These findings also add to the increasingly clear evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer's and dementia."

The study suggests that the slow and steady brain and cardiopulmonary activity linked to deep non-REM sleep are optimal for the function of the glymphatic system, the brain's waste removal system. The findings may also explain why some forms of anesthesia can result in cognitive dysfunction in older adults.

New research shows how the depth of sleep can impact our brain's ability to efficiently wash away waste and toxic proteins. Because sleep often becomes increasingly lighter and more disrupted as we become older, the study reinforces and potentially explains the links between aging, sleep deprivation, and heightened risk for Alzheimer's disease.

"Sleep is critical to the function of the brain's waste removal system and this study shows that the deeper the sleep the better," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicineat the University of Rochester Medical Center (URMC) and lead author of the study. "These findings also add to the increasingly clear evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer's and dementia."

The study, which appears in the journal Science Advances, indicates that the slow and steady brain and cardiopulmonary activity associated with deep non-REM sleep are optimal for the function of the glymphatic system, the brain's unique process of removing waste. The findings may also explain why some forms of anesthesia can lead to cognitive impairment in older adults.

The brain's system for removing waste is driven primarily by the pulsations of adjoining arteries, University of Rochester neuroscientists and mechanical engineers report in a new study. They also show that changes in the pulsations caused by high blood pressure slow the removal of waste, reducing its efficiency.

This might explain the association between high blood pressure and Alzheimer' disease, the researchers say. Alzheimer's, the most common cause of dementia among older adults, is characterized by abnormal clumps and tangled bundles of fibers in the brain.

The study, reported in Nature Communications, builds upon groundbreaking discoveries about the brain's waste removal system by Maiken Nedergaard, co-director of the University's Center for Translational Neuromedicine. Nedergaard and her colleagues were the first to describe how cerebrospinal fluid is pumped into brain tissue and flushes away waste. Subsequent research by her team has shown that this glymphatic waste removal system is more active while we sleep and can be damaged by stroke and trauma.

This latest research shows "in much greater depth and much greater precision than before" how the glymphatic system functions in the perivascular spaces that surround arteries in the outer brain membrane, says Douglas Kelley, an assistant professor of mechanical engineering and an expert in fluid dynamics. His lab is collaborating with Nedergaard's team as part of a $3.2 million National Institute on Aging grant.

For this study, Humberto Mestre, a PhD student in Nedergaard's lab, injected minute particles in the cerebrospinal fluid of mice, and then used two-photon microscopy to create videos showing the particles as they moved through the perivascular spaces.

What really happens when you sleep? You may be taking a break from consciousness when you snooze, but not all of your neurons are resting, Veasey says. While you rest, your brain solidifies the synapses involved in the important memories you want to keep (like the name of your new dentist) while pruning the synapses involved in less important memories (such as where you put your keys two nights ago).

Sleep also gives your brain a chance to clear out debris that accumulated during the day. In 2014, a team of scientists led by Maiken Nedergaard at the University of Rochester Medical Center published research suggesting that the brain rids itself of metabolic waste through a kind of plumbing system that works mainly while we sleep. Just as the lymphatic system clears unwanted waste from the rest of the body, what's called the glymphatic system eliminates debris and toxins from the brain and the central nervous system. Skimp on sleep, and this janitorial service can't keep up, so the rubbish starts to accumulate in your noggin.