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The Huntington Study Group, which was founded in 1993, is a research organization that is devoted to finding new treatments for Huntington's disease. The group includes more than 400 investigators and coordinators from over 100 research sites. Amy has been Instrumentally involved with our Huntington's disease program for more than twenty years. Her commitment to the Huntington's disease community is unparalleled. She is compassionate, knowledgeable, reliable and engaged at all levels of care for patients and families: local, regional, national and international. It is an honor to continue to work with and learn from her. Congratulations, Amy!

The Clinical Materials Services Unit (CMSU) has been awarded the contract to provide drug supply and distribution services to the for a new clinical research initiative that seeks to rapidly evaluate new drug candidates for Amyotrophic Lateral Sclerosis (ALS).

The HEALEY ALS Platform Trial -- which will be conducted by the Sean M. Healey & AMG Center at Massachusetts General Hospital -- is a new clinical trial initiative in which studies of investigational ALS treatments are tested and evaluated simultaneously. New treatments can be added to the study as they become available. This approach has already proven successful in the cancer field and will greatly accelerate therapy development by allowing investigators to test more drugs, increase patient access to trials, and reduce the cost by quickly and efficiently evaluating the effectiveness of multiple therapies.

Three drugs developed by Biohaven Pharmaceuticals, RA Pharma, and Clene Nanomedicine will be the first to participate in the platform trial. CMSU will be responsible for providing clinical supply chain management, packaging, labeling, distribution, and return services for all the drugs used in the platform study.

CMSU is led by senior research associate Cornelia Kamp, M.B.A., and director of Clinical and Business Affairs Patrick Bolger, R.Ph., M.B.A., and is a core research unit of the Center for Health + Technology (CHeT). Over the past 11 years CMSU has provided clinical supply services to 60 multi-center clinical trials conducted in the US, Canada, New Zealand and Australia supported with funding from the NINDS, NCCAMS, NICHD, NEI, Michael J. Fox Foundation, DOD, FDA, and numerous pharmaceutical and biotech companies. At any given time, CMSU supports between 15-20 clinical trials. CMSU recently moved to its new location at 150 Metro Park in Rochester.

Living microglia, genetically marked to glow green, in the cerebral cortex with magenta colored blood vessels from a mouse treated with URMC-099.

A new study published in the Journal of Neuroinflammation found that prophylactic treatment with URMC-099 -- a "broad spectrum" mixed-lineage kinase 3 inhibitor -- prevents neuroinflammation-associated cognitive impairment in a mouse model of orthopedic surgery-induced perioperative neurocognitive disorders (PND).

PND, a new term that encompasses postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, is the most common complication after routine surgical procedures, particularly in the elderly. Following surgery, such as hip replacement or fracture repair, up to 50 percent of patients experience cognitive disturbances like anxiety, irritability, hallucinations, or panic attacks, which can lead to more serious complications down the line. Currently, there are no FDA-approved therapies to treat it.

Developed in the laboratory of Harris A. "Handy" Gelbard, M.D., Ph.D., director of the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center, URMC-099 inhibits damaging innate immune responses that lead to inflammation in the brain and accompanying cognitive problems. Using animal models of diseases like HIV-1-associated neurocognitive disorders, Alzheimer's disease and multiple sclerosis, Gelbard has shown that the compound blocks enzymes called kinases (such as mixed lineage kinase type 3, or MLK3) that respond to inflammatory stressors inside and outside cells.

Gelbard and Niccolò Terrando, Ph.D., director of the Neuroinflammation and Cognitive Outcomes laboratory in the Department of Anesthesiology at Duke University Medical Center, used an orthopedic surgery mouse model that recapitulates features of clinical procedures such as a fracture repair or hip replacement, which are often associated with PND in frail subjects. In a pilot experiment, they treated one group of these mice with URMC-099 before and after surgery, and another group prior to surgery only. Gelbard and Terrando's teams, including first author Patrick Miller-Rhodes, a senior pre-doctoral student in the Neuroscience Graduate Program working in the Gelbard lab at URMC, measured the following:

• How the surgery affected the central nervous system and the immune cells (microglia) that reside there was evaluated using stereology and microscopy.
• Surgery-induced memory impairment was assessed using the "What-Where-When" and Memory Load Object Discrimination tasks.
• The acute peripheral immune response to surgery was assessed by cytokine/chemokine profiling and flow cytometry.
• Long-term fracture healing was assessed in fracture callouses using micro-computerized tomography and histomorphometry analyses.
• For additional details see the "Materials and Methods" section of the study

The team found that the surgery disrupted the blood brain barrier and activated microglia (a first line immune responder present in the inflamed brain), which led to impaired object place and identity discrimination when the mice were subject to the "What-Where-When" and Memory Load Object Discrimination tasks. Both URMC-099 dosing methods prevented the surgery-induced microgliosis (increase in the number of activated microglia) and cognitive impairment without affecting fracture healing.

"A major concern regarding the use of anti-inflammatory drugs for PND is whether they will affect fracture healing. We found that our preventive, time-limited treatment with URMC-099 didn't influence bone healing or long-term bone repair," said Gelbard and Terrando, professor of Neurology, Neuroscience, Microbiology and Immunology, and Pediatrics at URMC and associate professor of Anesthesiology at Duke University Medical Center, respectively. "These findings of improvement in cognition and normal fracture healing provide compelling evidence for the advancement of URMC-099 as a therapeutic option for PND."

"Right now we have nothing to treat this condition," said Mark A. Oldham, M.D., assistant professor in the department of Psychiatry at URMC who treats patients with PND. "We work hard to provide good medical care, including helping people sleep at night and making sure they are walking, eating and drinking, but it isn't clear that these efforts have any meaningful long-term impact."

According to Oldham, recent studies that track patients following an episode of PND show that many of them don't resolve completely, and that they have a new cognitive baseline after delirium.

"It is increasingly an accepted fact that after delirium, people have suffered some kind of neurological insult, which leaves them cognitively or functionally worse off than before the incident," he noted.

Next steps for the research include identifying definitive mechanisms for pain modulation, immune cell trafficking and neuro-immune characterization in PND. Gelbard and Terrando are tackling some of these questions with funds from the National Institutes of Health (RO1 AG057525). The current study was also funded by multiple grants from the NIH (P01MH64570, RO1 MH104147, RO1 AG057525 and F31 MH113504). The University of Rochester has four issued U.S. patents and multiple issued patents in foreign countries covering URMC-099.

The URMC Clinical Materials Services Unit (CMSU) has relocated to a newly renovated space at 150 Metro Park in Rochester. CMSU is a unique academic-based organization that provides consulting and supply chain logistics to small and large multi-center clinical trials.

The CMSU will hold an open house at the new facility on Tuesday, September 10 from 3:00 to 6:00pm.

CMSU was founded in 2008 when clinical researchers at URMC determined the need for a dedicated, on-site facility to manage entire supply chains in support of clinical trials. The CMSU is a core research unit of the Center for Health + Technology (CHeT) which is directed by Ray Dorsey, M.D.

CHeT faculty have been involved in the conduct of clinical research for more than 30 years and have conducted 133 clinical trials, involving 48 different sponsors, 43,000 study participants, and have played a leading role in bringing seven new drugs to market -- five for Parkinson's disease and two in Huntington's disease.

CMSU provides a full array of investigational drug and device packaging, labeling, distribution, and accountability services that support academic medical centers, pharmaceutical and biotech companies, and contract research organizations. CMSU, which is led by executive director Cornelia Kamp, M.B.A, is staffed by 8 dedicated full time employees with more than 150 years of collective pharmaceutical industry experience.

Over the past 11 years CMSU has provided clinical supply services to 60 multi-center clinical trials conducted in the US, Canada, New Zealand and Australia supported with funding from the NINDS, NCCAMS, NICHD, NEI, Michael J. Fox Foundation, DOD, FDA, and numerous pharmaceutical and biotech companies. At any given time, CMSU supports between 15-20 clinical trials.

CMSU also manages the logistical drug supply operations of NeuroNEXT, a NINDS-funded national network of academic medical centers dedicated to accelerating clinical research for neurological disorders. To date, CMSU has been involved in determining the drug supply requirements for 36 of the 67 proposals approved for clinical trials.

The CMSU was previously located in the BioVenture Center in Henrietta. The new 8,800+ square foot facility operates under current Good Manufacturing Practices (cGMP) and is licensed by the New York State Board of Pharmacy. The new location consolidates warehouse, office, and processing space and allows for the more efficient coordination and distribution of research materials.

The UR Medicine Mobile Stroke Unit (MSU) is now being dispatched to provide stroke care to patients throughout Monroe County. The MSU had been operating on a pilot basis in the City of Rochester since its launch in October 2018.

The MSU, which is operated in partnership with American Medical Response (AMR) and is the only unit of its kind in upstate New York, serves as an "emergency department on wheels" and brings the medical expertise and technology necessary to diagnose and treat stroke directly to the patient. Immediate care is essential during a stroke, during which millions of brain cells die every minute. However, if caught early, many stroke victims can make a full recovery.

It is estimated that 3,000 people in Monroe County suffer from a stroke every year. Stroke is the fifth leading cause of death and the number one cause of long-term disability in the U.S.

The MSU is equipped with a portable CT scanner that scans the patient's brain to determine the type of stroke they are experiencing. These scans and results from a mobile lab on the unit are transmitted to stroke experts at UR Medicine's Comprehensive Stroke Center at Strong Memorial Hospital, who consult via an on board teleconferencing system with the EMS personnel and determine if treatment -- in the form of the clot busting drug tissue plasminogen activator (tPA) -- can be administered immediately on scene.

"The ability to diagnose and start care in a patient's driveway is a game changer for our region," said Tarun Bhalla, M.D., Ph.D., Chief of Stroke and Cerebrovascular Surgery at the UR Medicine Comprehensive Stroke Center and director of the Mobile Stroke Unit initiative. "We are grateful to our partners in the EMS community for their cooperation in making this lifesaving technology available to stroke patients across Monroe County."

"The sooner patients receive care, the more likely they are to return to their lives," said Curtis Benesch, M.D., M.P.H., Chief of Stroke and Medical Director of the UR Medicine Comprehensive Stroke Center. "The time saved by delivering care directly to a stroke patient on scene can mean the difference between recovery of function or a lifetime of disability."

The MSU is dispatched by the City of Rochester/Monroe County 9-1-1 Emergency Communications Center in coordination with the following EMS agencies:

• Brighton Volunteer Ambulance
• Churchville Fire Department Rescue Squad
• CHS Mobile Integrated Health Care (Chili, Henrietta, Scottsville, Caledonia)
• Gates Volunteer Ambulance
• Greece Volunteer Ambulance
• Hilton Fire Department Ambulance
• Honeoye Falls-Mendon Volunteer Ambulance
• Irondequoit Ambulance
• Monroe Ambulance
• Northeast Quadrant Advanced Life Support
• Penfield Volunteer Emergency Ambulance Service
• Perinton Ambulance
• Pittsford Volunteer Ambulance
• Point Pleasant Fire Department Ambulance
• Rush Fire Department Ambulance
• RIT Ambulance
• Seabreeze Fire Department Ambulance
• Union Hill Volunteer Ambulance
• Webster Emergency Medical Services

"AMR is proud to partner with the University of Rochester and Monroe County to expand the available care options in Monroe County," said Tim Frost, regional director for AMR Western New York. "We are focused on providing the best possible care for the communities we serve, and bringing this new technology to the area is a testament to that."

An article appearing in Neurology Today, a publication of the American Academy of Neurology, describes how University of Rochester Medical Center (URMC) researchers have painstakingly compiled decades of patient data and developed a highly sensitive rating scale that has provided a detailed picture of Batten disease. This tool, which was developed 17 years ago, has set a standard for how to conduct natural history research in rare childhood neurodegenerative diseases.

A common challenge in the treatment and study of neurological disorders is that these diseases are often poorly understood. The complex manifestation of these conditions -- in which the appearance, severity, and progression of symptoms can vary widely -- combined with the difficulty in recruiting study participants with rare neurological disorders often conspire to hamper efforts to precisely define the disease. This is a major problem when it comes to clinical trials, where rigorously defined outcome measures are required to determine if an experimental treatment is effective.

CLN3 disease is such an example. The disorder is one of a family of conditions called neuronal ceroid lipofuscinoses (NCL), more commonly referred to as Batten disease, which are characterized by vision loss, movement disorders, seizures, and dementia. It is estimated 2 to 4 out of every 100,000 children in the U.S. have NCL. CLN3 disease, a juvenile onset form of NCL, is the most prevalent form of the disease.

Initiated in 2001 by URMC neurologists Frederick Marshall, M.D. and Jonathan Mink, M.D., the Unified Batten Disease Rating Scale (UBDRS) includes physical, seizure, behavioral, and vision assessments. Over time, the scale has been refined based on clinical observations. To date, University of Rochester Batten Disease researchers have used the UBDRS to perform almost 500 evaluations in more than 200 patients in the U.S. and around the world.

The development of the UBDRS was followed by the creation of a registry of known cases and the formation of the University of Rochester Batten Center in 2005. The center is co-directed by Mink and Erika Augustine, M.D. and includes Heather Adams, Ph.D. and Amy Vierhile, D.N.P on the leadership team and has become a leading center internationally for clinical research on all forms of Batten disease.

Read more about the development of the UBDRS in Neurology Today.

Two new grants from the National Institute of Neurological Disorders and Stroke (NINDS) will pave the way for new treatments for neuronal ceroid lipofuscinoses and Charcot Marie Tooth diseases, two groups of rare neurological disorders. The funding, which totals $10 million, will support new research programs led by University of Rochester Medical Center (URMC) neurologists Erika Augustine, M.D., and David Herrmann, M.B.B.Ch., and involve an international team of scientists and clinicians.

The funding comes from the NINDS Clinical Trial Readiness for Rare Neurological and Neuromuscular Diseases program, which was created to support studies that lay the groundwork for the next generation of treatments -- including gene replacement therapies -- currently under development. URMC researchers play leading roles in three of the five NINDS clinical trial readiness programs. URMC neurologist Rabi Tawil, M.D., is a co-director of an existing program that focuses on facioscapulohumeral muscular dystrophy.

"For many neurological diseases, there is a lack of preparedness to run the highest quality clinical trials," said Herrmann. "This includes making sure that you have teams in place and ways to effectively measure the effect of a new drug. And because you're dealing with a rare disease, getting enough patients into a trial is often a challenge."

"As the pipeline of potential new treatments expands, we have to be ready," said Augustine. "This means not just understanding the natural history of these disease, but to have clinical trial tools that are fit for purpose, both to meet regulatory requirements and to measure what is important to patients and families."

The research program led by Augustine will focus on Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) -- the most prevalent form of a family of neurological disorders commonly referred to as Batten diseases. The symptoms of CLN3 disease emerge in early childhood and involve vision loss, seizures, and impaired cognitive and motor function, all of which worsen as the disease progresses and youth typically die of disease complications by their twenties or thirties. There are currently no therapies available to modify the course of the disease.

The new funding will support a partnership between the University of Rochester Batten Center and the University of Hamburg in Germany to validate clinical outcomes and neuroimaging biomarkers that will precisely measure the symptoms and progression of CLN3 Disease and enable researchers to determine if new experimental therapies are effective. This funding builds upon more than 15-years of leading research by the Batten Center, which is directed by Jonathan Mink, M.D., Ph.D., in collaboration with Heather Adams, Ph.D. Frederick Marshall, M.D., Amy Vierhile, P.N.P., and Christopher Beck, Ph.D.

The program headed by Herrmann, who heads the URMC Neuromuscular Disease Program, will focus on Charcot Marie Tooth disease (CMT), a family of rare inherited peripheral neuropathies that is characterized by progressive weakness, imbalance, sensory loss, and gait abnormalities. While physical and occupational therapy, braces and other orthopedic devices, and surgery can help individuals cope with the disabling symptoms of the disease, there is currently no disease modifying treatment for CMT.

The project will involve researchers from URMC, the University of Iowa, the University of Pennsylvania, the University of Sydney in Australia, University College of London, and the C. Besta Neurological Institute in Milan, Italy. The team will be validating a clinical outcomes tool and new imaging technologies that measure the integrity and density of muscle tissue and nerve endings. The goal of the program is to generate a set of biomarkers and patient-centered measures of meaningful functional improvement that can ultimately be used in future clinical trials.

Gretchen L. Birbeck, MD, MPH, Professor, Department of Neurology, University of Rochester Medical Center, has dedicated much of her career to improving care for neurological disorders in sub-Saharan Africa. Her work in Zambia initially focused on understanding the burden of epilepsy and barriers to care for patients with epilepsy, and this early work led to studies addressing the pathophysiology and determinants of outcomes of pediatric cerebral malaria in both Malawi and Zambia. She has also contributed to our understanding of neurological complications of HIV and the overall burden of neurological diseases in sub-Saharan Africa.

Dr. Birbeck has worked to improve the neurologic training of healthcare workers and to develop research capacity in both Zambia and Malawi. Moreover, she has been a true pioneer in the field of global neurology as the first to demonstrate how one could have a viable academic neurology career while working in a low-resourced setting. In fact, she has maintained continuous NIH funding for her work in sub-Saharan Africa for the past 16 years. For her work, she has been named Fellow of the American Academy of Neurology, the American Neurologic Association, and the Royal Society of Tropical Medicine & Hygiene; and has received numerous awards. She is a U.S. Paul Rogers Society Ambassador for Global Health Research and was recognized by the International League Against Epilepsy as an Ambassador for Epilepsy.

Her trailblazing work serves as the foundation for the field of global neurology, and she has mentored the majority of neurologists in academic global neurology today. Birbeck's dedication to improving neurological care in sub-Saharan Africa and building the careers of junior African and U.S. neurologists and scientists is unparalleled.