MedStar Georgetown Specialist Leads Targeting of Huntington’s Disease Symptoms Through New Guidelines

An international group of experts, led by MedStar Georgetown University Hospital’s Karen Anderson, MD, recently published new clinical guidelines focusing on the treatment of behavioral symptoms seen in patients with Huntington’s disease.

Huntington’s disease is a fatal genetic disorder that impairs physical and mental abilities as movement-controlling cells die in the brain. It’s estimated that 70% of American patients with the disease do not receive specialist care; instead seeking treatment from general practitioners, general neurologists, and psychiatrists.

“These guidelines convey the important message that we have treatments available now for many neuropsychiatric symptoms of HD. This should encourage patients to seek care. They also help non-specialist clinicians understand that HD is a not a hopeless condition,” explains Dr. Anderson, director of the Huntington’s Disease Care, Education, and Research Center (HDCERC), a joint program between MedStar Georgetown University Hospital and Georgetown University Medical Center.

The guidelines, published in the Journal of Huntington’s Disease, provide primary caregivers with a stronger set of tools and specialist-led strategies to treat five behavioral symptoms of the disease: agitation, anxiety, apathy, psychosis, and sleep disorders.

Before publication, Dr. Anderson and the panel of nine others submitted ideas to Huntington’s disease experts around the world to reach consensus. Clinical Practice Guidelines (CPG) like these can be relied on in the absence of randomized clinical trial evidence, which is harder to obtain when studying rarer diseases.

“We encourage patients and families to use these guidelines to partner with their clinicians when seeking care since these symptoms often have a huge impact on patients’ wellbeing and their relationships with individuals close to them,” advised Dr. Anderson.

Currently, there is no treatment available to slow, stop, or reverse the course of Huntington’s disease, according to the Centers for Disease Control.

For more on the newly published guidelines, visit: https://www.iospress.nl/ios_news/expert-based-clinical-guidelines-focus-on-behavioral-symptoms-in-huntingtons-disease/

 

 

 

 

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MedStar Georgetown First in the Washington, D.C. Area to Perform Minimally Invasive Adult Brain Surgery Using a Robot

(Washington, D.C.) - Epilepsy patients looking for a minimally invasive alternative for brain surgery have a new option thanks to a novel tool that lets surgeons perform brain surgery with the help of a robot.

MedStar Georgetown is the first and only center in the Washington, D.C. area to offer this new option for adults with epilepsy.

ROSA Brain™ is a surgical navigation and positioning system using robotic technology that allows surgeons, through a tiny three millimeter opening in the skull, to place electrodes, which detect seizures in the brain.  Traditional methods require a more invasive craniotomy and shaving a patient’s head.

“About 30 percent of patients with epilepsy don’t respond to medication,” says Christopher Kalhorn, M.D., FACS, neurosurgeon and surgical director of the Movement Disorders Program and the Epilepsy Program at MedStar Georgetown University Hospital.

“For this group of people who don’t respond to medicine and for whom debilitating seizures are a daily threat, surgery can be a good option for eliminating their seizures.”

The surgeon uses ROSA Brain and its planning software to create a 3D map of the patient’s brain and plan out the pathways needed to carry out the procedure. ROSA Brain is aligned to the trajectories outlined by the surgical plan, and the surgeon carries out the surgery using the robot as a guide. ROSA Brain provides robotic alignment of the planned pathway which allows the surgeon to access deep brain targets for the placement of electrodes, all without a craniotomy.

“Conventional brain surgery for epilepsy requires a craniotomy, which is the surgical removal of part of the bone from the skull to expose the brain,” says Dr. Kalhorn.

This common surgery is invasive and can lead to long recovery times.

“Using Rosa Brain through a tiny opening in the skull, I can offer a much less invasive option for my patients who recover quicker and with less pain than before.”

ROSA RobotAccording to the U.S. Centers for Disease Control and Prevention 3.4 million Americans either take medication to try to control seizures, or have had at least one seizure in the past year.

Minimally invasive surgery using ROSA Brain may allow surgeons to lower operating time and eliminate the need of traditional craniotomies.

“The beauty of this technology is while it’s mainly used for epilepsy surgery, it can also be used for other brain surgeries like biopsies, endoscopic brain surgeries as well as Deep Brain Stimulation (DBS) for Parkinson’s disease and other movement disorders,” says Dr. Kalhorn.

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Georgetown Study Investigates Memory Improvement Through Nicotine Dosing

WASHINGTON --  Can nicotine slow or stop memory loss in people experiencing mild memory problems, or mild cognitive impairment (MCI)? A new study being conducted at Georgetown University Medical Center aims to find out.

Recent studies have suggested that one of the causes of memory disorders may be a reduction in a particular chemical substance in the brain. This chemical substance, known as acetylcholine, is thought to act on certain brain cells in a specific way, helping us to remember and use memories as well as affect our mood.

In people with MCI (and Alzheimer’s disease), the level of acetylcholine may be changed, and this may impair brain functioning. Preliminary studies have suggested that shorter-term administration of nicotine appears to improve memory in patients with mild memory loss and early Alzheimer’s disease (AD). It has been known for years that nicotine imitates many of the actions of acetylcholine.

To expand on this finding, a clinical trial led by Georgetown’s principal investigator, R. Scott Turner, MD, PhD, will explore whether nicotine may act to improve memory loss symptoms over the longer term and whether it may help to delay the progression of memory loss symptoms.

“We are increasingly able to detect those at risk for future Alzheimer's disease in order to perhaps slow or stop their progression to dementia,” says Turner. “About 10-15% of those diagnosed with mild cognitive impairment (MCI) will advance to dementia each year most commonly due to Alzheimer's disease – with a total risk of greater than 50% after 5 years. This new study is seeking volunteers with MCI to test whether treatment with a daily Nicotine skin patch can slow or stop further cognitive decline.”

This phase 2 randomized clinical trial is being conducted at approximately 30 to 40 clinical trial sites across the United States and will enroll 300 participants. Participants will wear a skin patch, containing either nicotine or placebo, for approximately 16 hours per day for two years.

Half of the participants will receive transdermal nicotine (nicotine by skin patch) called a “nicotine patch” with a dose of 7 mg per day increasing to 21 mg per day. The other half (the control group) will receive an identical patch, which does not contain an active dose of nicotine, called a “placebo patch.” The placebo patch contains a small amount of nicotine that cannot pass into the skin or be absorbed by the body.

Given that this is a randomized trial, neither the investigator nor the participant will know which group they are in.

During the first visit, participants will undergo standard physical and cognitive testing with the addition of an electrocardiogram (ECG). They will also be given a memory and thinking skills test that will be written as well as administered on an electronic device.

Some side effects could include sleepiness, diarrhea, stomach ache, muscle pain or joint pain  (reported by 3-9 percent of patients using the nicotine patch) and reddening or irritation of the skin where the patch is applied (reported by 17 percent of patients using the patch).

“Since we don't know all the possible risks and benefits as yet of Nicotine patch treatment in individuals with MCI, we advise against taking the drug for this purpose outside of the study,” says Turner.

Study participants must be between the ages of 55-90 and have a study partner who can accompany them to all appointments.

Full study criteria are available at ClinicalTrials.gov.

To learn more about this or other clinical trials, please contact Carolyn Ward, program coordinator of the Memory Disorders Program at (202) 784-6671, [email protected].

The study is sponsored by the National Institute on Aging and is being conducted by the

Alzheimer’s Therapeutic Research Institute (ATRI) with Vanderbilt University through a grant from the National Institute on Aging (NIA).  Turner conducts additional clinical research supported by funding to Georgetown University from Lilly, Biogen, Merck, Acadia, and Toyama as well as the National Institutes of Health and Department of Defense.

 

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A Better Brain Tumor Cure is Right Under Your Nose at MedStar Georgetown University Hospital

When D.C. resident Dawn Goodloe started having trouble reading road signs and licenses plates in the middle of last year, her brain jumped to the most logical conclusion.

“I hadn’t been to the eye doctor for a couple of years, so I just figured I needed a new prescription,” says the 47-year-old legal assistant.

However, after vision correction failed to clear things up, an MRI revealed the shocking truth: her brain was the problem all along. Those MRI images showed a meningioma – a usually benign tumor – pushing into her optic nerve.

"I had absolutely no idea that I was walking around with a brain tumor, other than the fact that my vision was really blurry,” Goodloe says. "I wasn't having headaches, I wasn't having dizziness. Nothing.”

Plans to buy a new pair of glasses suddenly jumped to a potentially life-changing brain surgery.

“I was beyond fearful because I’ve never been in the hospital for anything, other than to have my daughter. All I could think about were worst case scenarios,” Goodloe says.

Just a few days later at MedStar Georgetown University Hospital, Neurosurgeon Amjad Anaizi, MD, recommended a newly developed surgical procedure for meningioma: the expanded endoscopic endonasal approach. That means using advanced instruments to remove the entire tumor through Goodloe’s nose.

Not only is it possible but, with the right training and expertise, doctors say the operation is better for the patient’s overall recovery.

"MedStar Georgetown is one of the few places in the country that offers an endonasal treatment for this particular kind of tumor," says Anaizi. “It avoids incision of the head, avoids the pain associated with that, and avoids any manipulation of the normal brain."

According to Anaizi, meningioma is traditionally removed by craniotomy, or surgery through the top of the head. The endoscopic endonasal approach gets to the tumor from underneath by navigating the nasal cavity and sinuses. It’s a more direct route and often leaves the patient looking like they didn’t have surgery at all. At MedStar Georgetown, Anaizi tag-teams the operations with Otolaryngologist Timothy DeKlotz, MD.

“I think having two sets of eyes on a complicated problem is always helpful,” says DeKlotz. “The combination of two endoscopic trained skull-base surgeons who work together on these is very uncommon.”

DeKlotz and Anaizi in SurgeryThe roughly six and a half hour procedure begins with DeKlotz opening up the nose and sinuses. Then, Anaizi carefully removes the tumor from beneath the membrane on which it sits. The operation relies on longer tools that can reach the tumor from outside the head, and a high quality camera piloted by Dr. DeKlotz.

“It gives us access to tumors and the ability to manage certain diseases that were not able to be effectively treated at all.” DeKlotz says. “A lot of it comes from the experience of working together, knowing the limits, and continuing to push those limits as we learn more about what can be done safely and effectively.”

Goodloe’s tumor was not cancerous, but her eyesight continued to get worse at it grew. She had a big decision to make. Any surgery could potentially damage her optic nerve, carotid artery and other complex blood vessels. However, she was determined to get better.

"I was really scared because I was facing the threat of not being able to watch my daughter grow up, or grow old with my husband and I didn’t know what was going to happen."

In the end, she leaned on confidence in her two new specialists and elected to have the endoscopic endonasal operation.

It was the right decision.

Goodloe was placed under anesthesia throughout the procedure and later woke to a much clearer image of her recovery room. The tumor was gone. Her vision had improved drastically. The operation was a success.

Dawn Goodloe with her daughter"I opened my eyes and I could see. It was amazing. I'll never forget that feeling," she says.

In recovery, Goodloe remained in the hospital for four days as her nose was packed with gauze. There, her nasal cavity began to heal. For a week, she only breathed out of her mouth and avoided blowing her nose. Those brief adjustments ended up paying off in the end and after only two months she returned to work.

“When I came back to work, I think everyone was expecting me to have a shaved head and a big scar on the side,” she says. “I didn’t look like I had surgery. They could not tell.”

 “We get people home more quickly with the endoscopic endonasal approach,” DeKlotz says. “The healing process involves fewer complications and it happens a lot faster.”

“It’s dramatic,” says Dr. Anaizi. “There’s more recent evidence that shows clear advantages. The visual outcomes are better and the seizure rates are lower.”

For Goodloe, it meant getting back the one precious thing her tumor was slowly taking away: the clear sight of her husband and 10-year-old daughter.

 “It gets better every day. I feel myself getting stronger every day. I’m just happy to be alive and here and have amazing doctors who helped me,” she says.

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MedStar Georgetown First Hospital in Washington, D.C. Metropolitan Area to Use New Deep Brain Stimulation System for Parkinson’s Disease

MedStar Georgetown University Hospital is the first center in the Washington, D.C. metropolitan area to treat a Parkinson’s disease patient with a new and recently FDA-approved Deep Brain Stimulation (DBS) system that allows for more precision and more patient convenience.

DBS technology has been used in the United States for about 15 years and treats the symptoms of Parkinson’s by stimulating a targeted region of the brain through surgically implanted leads that are powered by a device called an implantable pulse generator (IPG).

Vercise SystemThe new DBS system called Vercise™ is made by Boston Scientific and is completely wireless.

“The patient we just implanted with this new system has severe advanced Parkinson’s so for him this technology means he should be able to greatly reduce the amount of medication he’s taking to control his PD symptoms,” says Neurosurgeon Chris Kalhorn, MD, director of the Movement Disorders Surgical Program at MedStar Georgetown.

Dr. Kalhorn implanted the device during a five-hour surgery in early March.

“Additionally, this new wireless system is the smallest rechargeable DBS device available in the United States and the battery doesn’t have to be replaced for at least 15 years, instead of five years with most traditional DBS systems,” says Dr. Kalhorn.

Vercise DBS versus Traditional DBS

 Unlike traditional DBS systems that are built from pacemaker technology, the Vercise DBS System was developed from a foundation of cochlear implant technology and the precise stimulation of auditory nerves it uses to replicate hearing. This innovative approach and proprietary technology allows for greater control and enables physicians to deliver a prescribed amount of stimulation.

“The Vercise DBS System helps me provide better outcomes for my patients with this debilitating disease. It has the ability to adapt therapy to address fluctuations in symptoms and the progressive nature of the condition for patient-specific programming and provides me with more precision than ever before,” says Dr. Kalhorn.

The Vercise DBS System has been approved in Europe since 2012.

Deep Brain Stimulation is for patients with moderate to advanced Parkinson’s that responds to levodopa (L-DOPA) but whose symptoms are no longer well controlled with medication.

What is Parkinson’s disease?

Parkinson’s disease is a progressive, neurological condition that affects nearly one million people in the U.S. and 10 million people worldwide. It is the second most common neurodegenerative condition after Alzheimer’s disease. Most people with PD are diagnosed after age 60 and the condition is more common in men than women.

 What Causes Parkinson’s?

The exact cause of PD is unknown, but researchers believe it may be due to a combination of genetic and environmental factors. PD results in a deficiency of dopamine-producing cells in the substantia nigra region of the brain. This shortage of dopamine, a chemical used to transmit signals in the motor regions, reduces the brain’s ability to control or initiate movement. Its progressive nature and slow onset makes the condition difficult to diagnose.

PD Symptoms

The motor symptoms of Parkinson’s disease may include resting tremor, muscle rigidity, slow movements known as bradykinesia and postural instability. Non-motor symptoms can include depression and anxiety, problems sleeping, low blood pressure when standing, speech and swallowing problems and loss of smell.

 

 

 

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MedStar Georgetown Awarded Advanced Certification as a Comprehensive Stroke Center

Comprehensive-Stroke-Center-The-Joint-Commission-Certification-BadgeMedStar Georgetown University Hospital recently earned The Joint Commission’s Gold Seal of Approval® and the American Heart Association/American Stroke Association’s Heart-Check mark for Advanced Certification for Comprehensive Stroke Centers.

MedStar Georgetown is now one of only 156 healthcare organizations in the United States to have earned this certification in highly-specialized stroke care. To be eligible for certification, hospitals must demonstrate compliance with stroke-related standards as a Primary Stroke Center and meet additional requirements, including those related to advanced imaging capabilities, 24/7 availability of specialized treatments, and providing staff with the unique education and competencies to care for complex stroke patients. 

“We have a superb multi-disciplinary team of providers, nurses, scientists and educators who are dedicated to providing the highest level of care for patients with cerebrovascular disease,” said Dr. Andrew Stemer, director of Stroke Neurology at MedStar Georgetown. “The Joint Commission recognizing MedStar Georgetown as a Comprehensive Stroke Center confirms that we are one of the elite programs in the nation.”

Achieving certification as a Comprehensive Stroke Center was the culmination of years of hard work by a multidisciplinary team, including stroke care experts from: Neurology, Neurosurgery, Neuro Critical Care, Emergency Medicine, Neuroradiology, Neuro Interventional Radiology, Case Management, Physical Medicine and Rehabilitation, Regulatory Readiness, and Physiatry. MedStar Georgetown’s stroke team is anchored by Dr. Stemer and the Hospital’s specially-trained stroke neurologists, as well as a dedicated nurse practitioner, nurse navigator, and program coordinator. The Hospital’s stroke team collaborated to evaluate and enhance the care received by stroke patients, which included implementing new policies and providing additional training for associates, as well as expanding the collection and review of key data elements critical to the care of stroke patients.

“This certification shows our commitment to a higher standard of service and quality of care for our patients,” said MedStar Georgetown’s Stroke Program Coordinator Amanda Lantzy, MSN, RN. “Our expanded services ensure that we can treat and provide excellent quality of care to the most complex stroke patients around the clock. We have dedicated, specially-trained clinicians available at any time of day or night, including board-certified vascular neurologists. Having their expertise readily available ensures our patients are receiving the care they need which provides better long term outcomes for stroke survivors.”

"By achieving this advanced certification, MedStar Georgetown University Hospital has thoroughly demonstrated the greatest level of commitment to the care of its patients with a complex stroke condition,” said Dr. Mark R. Chassin, president and CEO of The Joint Commission. “Certification is a voluntary process and The Joint Commission commends MedStar Georgetown for successfully undertaking this challenge to elevate the standard of its care for the community it serves.”

Nancy Brown, chief executive officer of the American Heart Association/American Stroke Association remarked, “The American Heart Association/American Stroke Association congratulates MedStar Georgetown University Hospital on achieving Comprehensive Stroke Center certification. Meeting the standards for Comprehensive Stroke Center certification represents a commitment to deliver high quality care to all patients affected by stroke.”

This certification provides validation for the public that MedStar Georgetown maintains a consistently high level of quality, using effective, data-driven performance improvement practices. Above all, patients who receive stroke care at MedStar Georgetown know that they are being cared for by nationally-recognized experts who are part of a well-coordinated and highly-specialized team.

MedStar Georgetown Stoke Team

 

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Protein Associated with Parkinson’s Disease Linked to Human Upper GI Tract Infections

WASHINGTON  —Acute and chronic infections in a person’s upper gastrointestinal tract appear to be linked to Parkinson’s disease, say scientists at Georgetown University Medical Center and their collaborators at the National Institutes of Health and other institutions.

Their study, published in the Journal of Innate Immunity, finds that alpha-Synuclein (αS), the protein implicated in Parkinson’s disease and other forms of neurodegenerative diseases, is released when an infection occurs in the upper GI tract (the esophagus, stomach and duodenum) inducing an immune response as part of the body’s innate immune system. The researchers say that these findings suggest that frequent or chronic upper GI infections could overwhelm the body’s capacity to clear αS, leading to disease.

image-of-brainThis largely federally-funded study helps clarify the function of αS, which is poorly understood, says the study’s senior investigator, Michael Zasloff, MD, PhD, professor of surgery and pediatrics at Georgetown University School of Medicine and scientific director of the MedStar Georgetown Transplant Institute.

This research builds upon prior studies that showed in autopsied material from individuals at very early as well as later stages of Parkinson’s, that the buildup of αS actually begins in the enteric nervous system (nerves in the GI tract). Animal studies have further shown that microbes in the GI tract can induce formation of toxic aggregates in the enteric nervous system, which can then travel up to the brain.

Zasloff and his colleagues studied biopsy samples, collected at the University of Oklahoma Health Sciences Center, from 42 children with upper GI distress. They also looked at another population of 14 MedStar Georgetown University Hospital patients who received an intestinal transplant. This second group had documented cases of infection by Norovirus, a common cause of upper GI infection.

The biopsies showed that expression of αS in enteric nerves of the upper GI tract in these children positively correlated with the degree of acute and chronic inflammation in the intestinal wall. Some highly monitored transplant patients expressed αS as Norovirus was infecting them.

Researchers also showed that human αS could potently attract human immune cells such as macrophages and neutrophils and could “turn on” dendritic cells to alert the immune system of the specific pathogen encountered.

As Zasloff explains, “When expressed in normal amounts following an infection of the upper GI tract, αS is a good molecule. It is protective. The nervous system within the wall of the GI tract detects the presence of a pathogen and responds by releasing αS. αS then attracts white blood cells to the site where it has been released. In addition, αS produced in one nerve can spread to others with which it communicates thereby protecting a large field. By this means, the nervous system can protect both itself as well as the GI tract as a whole in the setting of an infection.”

He adds, “It is well known from animal studies that αS produced in the enteric nervous system can use the nerves connecting the GI tract to the brainstem as an escalator, trafficking αS from the gut to the brain and spreading to centers within the central nervous system.

“But too much αS — such as from multiple or chronic infections — becomes toxic because the system that disposes of αS is overwhelmed, nerves are damaged by the toxic aggregates that form and chronic inflammation ensues. Damage occurs both within the nervous system of the GI tract and the brain.”

Zasloff says the new findings “make sense” of observations made in Parkinson’s disease patients, such as the presence of chronic constipation from damage to the enteric nervous system that develops decades before brain symptoms become apparent and that chronic upper GI distress is relatively common in people who develop Parkinson’s.

Zasloff adds that the publication of this study coincides with the start of a clinical trial targeting the accumulation of αS in the enteric nervous system. The phase 1/2a study is examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of an oral drug, ENT-01, a synthetic version of squalamine, a natural steroid made by the dogfish shark, to relieve constipation associated with Parkinson's disease. Research recently published by Zasloff and collaborators demonstrated that squalamine both reduced the formation of toxic αS clumps and their toxicity, in animal experiments. The clinical trial, being conducted in the US, is sponsored by Enterin, Inc.


The study’s lead author was Ethan Stolzenberg MD, PhD, from the University of Oklahoma and its co-senior author was Denise Barbut, MD, FRCP, Enterin, Inc.

Other scientists contributing to the study include De Yang MD, PhD, Joost J. Oppenheim, MD, and Ad Bax, PhD from the National Institutes of Health, E.Y. Lee, and Gerard C. L. Wong, PhD, from the University of California, Los Angeles. Collaborators from Georgetown are Deborah Berry, PhD, Alexander Kroemer, MD, Supti Sen, Stuart Kaufman, MD, Thomas M. Fishbein, MD, and Brent Harris, MD, PhD.

Zasloff is founder, chairman and CEO of Enterin and Barbut is co-founder of Enterin, president and chief medical officer of the company.

The study was funded by the Intramural Research Program of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK029047), the University of Oklahoma, and UCLA training grants from the National Institute of General Medical Sciences (T32GM008185, T32GM008042).

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Study: Cancer Drug Restores Important Brain Dopamine in Parkinson’s Patients

WASHINGTON — A small phase I study provides molecular evidence that an FDA-approved drug for leukemia significantly increased brain dopamine and reduced toxic proteins linked to disease progression in patients with Parkinson’s disease or dementia with Lewy bodies. Dopamine is the brain chemical (neurotransmitter) lost as a result of death of dopamine-producing neurons in these neurodegenerative diseases. 

Researchers from Georgetown University Medical Center (GUMC), say the findings, described in the Journal of Parkinson’s Disease, support improved clinical outcomes observed and first reported at the Society for Neuroscience annual meeting in October 2015.

The study tested nilotinib taken daily for six months. A much smaller dose of nilotinib (150 or 300 mg once daily) was used compared to the dose for chronic myelogenous leukemia (300-400 mg twice daily). Twelve patients were enrolled in the clinical trial — one patient withdrew due to an adverse event. Researchers say the drug appears to be safe and well tolerated in the remaining 11 participants who completed the study.

In addition to safety, the researchers also examined biological markers in the blood and cerebral spinal fluid as well as cognitive, motor and non-motor improvement. They found significant signs that nilotinib may provide benefit for patients with these neurodegenerative diseases.

“These results need to be viewed with caution and further validated in larger placebo controlled trials, because this study was small, the patients were very different from each other, and there was no placebo,” says the study’s senior investigator, Charbel Moussa, MD, PhD, scientific and clinical research director of the GUMC Translational Neurotherpeutics Program.

Among the biomarker findings were that:

  • The level of the dopamine metabolite homovanillic acid — an indicator that dopamine is being produced — steadily doubled, even with the loss of most dopamine neurons. Most study participants were able to stop using, or reduce their use of, dopamine replacement therapies;
  • The level of the Parkinson's related oxidative stress marker DJ-1 — an indicator that dopamine-producing neurons are dying — was reduced more than 50 percent after niltonib treatment; and
  • The levels of cell death markers (NSE, S100B and tau) were significantly reduced in cerebrospinal fluid (CSF) suggesting reduced neuronal cell death.

In addition, Moussa adds that it appears nilotinib attenuated the loss of CSF alpha-synuclein, a toxic protein that accumulates within neurons, resulting in reduced CSF levels in both Parkinson’s disease and dementia with Lewy bodies.

The researchers also said that all 11 patients who tolerated the drug reported meaningful clinical improvements. All patients were at mid-advanced stages of Parkinsonism and they all had mild to severe cognitive impairment.

“Patients progressively improved in motor and cognitive functions as long as they were on the drug — despite the decreased use of dopamine replacement therapies in those participants with Parkinson’s and dementia with Lewy bodies,” says the study’s lead author, Fernando Pagan, MD, medical director of the GUMC Translational Neurotherpeutics Program and director of the Movement Disorders Program at MedStar Georgetown University Hospital.

But three months after withdrawal of the drug, participants returned to the same reduced cognitive and motor state they had before the study began, Pagan adds.

Some serious side effects were reported including one patient who withdrew at week four of treatment due to heart attack and three incidents of urinary tract infection or pneumonia. The researchers say these incidents are not uncommon in this patient population, and additional studies are needed to determine if the adverse events are related to use of nilotinib.

“Long term safety of nilotinib is a priority, so it is important that further studies be conducted to determine the safest and most effective dose in Parkinson’s, says Pagan.

The researchers designed the clinical trial to translate several notable observations in the laboratory. The preclinical studies, led by Moussa, showed that nilotinib, a tyrosine kinase inhibitor, effectively penetrates the blood-brain barrier and destroys toxic proteins that build up in Parkinson’s disease and dementia by turning on the “garbage disposal machinery” inside neurons.

Their published studies also showed nilotinib increases the levels of the dopamine neurotransmitter — the chemical lost as a result of neuronal destruction due to toxic protein accumulation — and improves motor and cognitive outcomes in Parkinson’s and Alzheimer’s disease animal models.

“Our hope is to clarify the benefits of nilotinib to patients in a much larger and well controlled study. This was a very promising start,” Moussa says. “If these data hold out in further studies, nilotinib would be the most important treatment for Parkinsonism since the discovery of Levodopa almost 50 years ago.”  

He adds, “Additionally, if we can validate nilotinib effects on cognition in upcoming larger and placebo controlled trials, this drug could become one of the first treatments for dementia with Lewy bodies, which has no cure, and possibly other dementias.”

Two randomized, placebo-controlled phase II clinical trials are planned for summer/fall in Parkinson’s and Alzheimer’s diseases. The Translational Neurotherpeutics Program is also planning a small trial in ALS (Lou Gherig’s disease).

According to Novartis, the cost (as of Oct. 2015) of nilotinib for the treatment of CML was about $10,360 a month for 800 mg daily. The dose used in this study was lower —  150 and 300 mg daily.

The phase I study received philanthropic funding and was supported by the Georgetown-Howard Universities Center for Clinical and Translational Science.

Moussa is listed as an inventor on a patent application that Georgetown University filed related to the use of nilotinib and other tyrosine kinase inhibitors for the treatment of neurodegenerative diseases. 

Study co-authors include Ellen H. Valadez, MD; Yasar Tores-Yaghi, MD; Reversa R. Mills, MD; Barbara M., Wilmarth, NP; Hellen Howard, RN; Connell Dunn; Alexis Carlson; Sean L. Rogers, MD, PhD;  and Ramsey (Drew) Falconer, MD; from the National Parkinson’s Foundation Center for Excellence, the Translational Neurotherapeutics Program, and the Movement Disorders Program at the MedStar Georgetown University Hospital; Michaeline Hebron, and Xu Huang, and Jaeil Ahn, PhD, Georgetown University Medical Center.

The researchers represent the MedStar Georgetown Movement Disorders Program, GUMC’s Translational Neurotherapeutics Program, the Laboratory for Dementia and Parkinsonism, the Georgetown-Howard Universities Center for Clinical and Translational Science Clinical Research and the department of biostatistics.

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Charbel Moussa, MD, PhD and Fernando Pagan, MD
Charbel Moussa, MD, PhD and Fernando Pagan, MD

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Meet Dr. Pagan

Georgetown Seeks Volunteers for New Immunotherapy Clinical Trial for Alzheimer’s

WASHINGTON — The Memory Disorders Program at Georgetown University is seeking volunteers to participate in an international clinical trial of a drug that, in an early phase study, has demonstrated promise in slowing mental decline in Alzheimer’s disease. Georgetown is the only institution in the greater Washington, DC, area offering access to the phase 3 study of the investigational immunotherapy drug aducanumab.

The multicenter clinical trial is designed to evaluate the benefit and safety of the drug in patients with mild Alzheimer’s disease, says Georgetown’s principal investigator, R. Scott Turner, MD, PhD., who sees patients at MedStar Georgetown University Hospital.

“We are excited to offer this clinical trial to our patients. It is the only study to date that has shown some benefit in early Alzheimer’s disease, both in terms of symptom management and disease modification,” he says. “This advanced study is needed to confirm if and how well the drug works, and at what dose.”

The study is sponsored by Biogen Idec, which manufactures aducanumab, an immunotherapy designed to reduce beta amyloid plaque in the brain. Progressive accumulation of the protein is one of the hallmarks of Alzheimer’s disease.

In data presented at the Alzheimer’s Association International Conference in July, Biogen announced interim analysis of an early phase study that found a significant reduction of beta amyloid plaque build up in the brain. It also showed a slowing of clinical impairment in patients with mild disease who were treated for nearly a year with a monthly dose of aducanumab.

The only side effect of concern seen in previous studies was inflammation of the brain, found in a small fraction of patients, Turner says. “However, this was detected by brain imaging only — there were no symptoms — and was transient and reversible. During our study, participants will be carefully monitored by frequent examinations and brain MRI scans.”

The primary objective of the new study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment in participants with mild Alzheimer’s disease as compared with a placebo. A high dose and low dose will be tested, and the drug is administered intravenously.

Some participants will be randomly assigned to a group that is given a low dose, or another group given a higher dose, or to a group given a placebo drug (a process known as randomization). The study will also be “blinded” — neither individuals nor researchers will know which group participants belong to.

To enter the study, patients must have evidence of beta amyloid accumulation (confirmed by a PET scan) and meet clinical criteria for mild Alzheimer’s disease. Participants must be between the ages of 50-85 and have a study partner who can accompany them to all appointments.

Full study criteria are available at ClinicalTrials.gov.  

To learn more about this or other clinical trials, please contact Carolyn Ward, program coordinator of the Memory Disorders Program at (202) 784-6671 or [email protected].

Research support to Georgetown University has been provided by Eli Lilly and Co., Biogen, Toyama Chemical Co., AstraZeneca, Novartis and the National Institutes of Health.

About Georgetown University Medical Center
Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award (UL1TR001409-01) from the National Institutes of Health.

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Alzheimer's

Huntington Disease Center at Georgetown Designated As Center of Excellence

WASHINGTON (Feb. 22, 2016) — The Huntington’s Disease Society of America (HDSA) has designated the Huntington Disease Care, Education and Research Center at Georgetown as an HDSA Center of Excellence for 2016. The designation comes with a grant to support services for Huntington disease patients and their families at the center, a collaboration between Georgetown University Medical Center (GUMC) and MedStar Georgetown University Hospital with generous support from the Griffin Foundation.

The Huntington Disease Care, Education and Research Center opened in 2012, making it the first comprehensive, multidisciplinary center in the Washington area to focus on treatment, patient education and research for Huntington disease. Karen E. Anderson, MD, was named director of the center in 2013.

“We are thrilled to be designated a Center of Excellence. This designation will promote our high quality of care and research to Huntington Disease families in the region, since the HDSA is so widely recognized in the community,” says Anderson, a neuropsychiatrist with dual appointments in the departments of psychiatry and neurology.

Huntington disease is a hereditary, progressively degenerative brain disorder for which there is no cure. Symptoms include involuntary movements, cognitive decline and emotional disturbances that slowly diminish the ability to walk, talk and reason. Treating people with Huntington disease requires a skilled clinical team to make an accurate diagnosis and provide comprehensive care.

According to the HDSA, the goal of the Center of Excellence program is to increase access to the best possible multidisciplinary clinical care and services for individuals affected by Huntington disease. In addition to clinical and social services, the centers provide professional and lay education in the geographic areas they serve, and are involved in clinical research and work with HDSA locally and nationally in its efforts to continually improve the lives of patients and families affected by Huntington disease.

“Our Georgetown Huntington disease center expanded quickly outside of Washington, so we could offer comprehensive services for patients and their families in Maryland and Virginia, too,” says Carlo Tornatore, MD, chair of neurology at MedStar Georgetown and professor of neurology at Georgetown School of Medicine. “All three centers host multiple services provided by a social worker, neurologist, neuropsychiatrist, neuropsychologist, genetic counselor, speech therapist and occupational therapist. Patients also have access to clinical trials for emerging therapies.”

The vast array of expertise is fostered by the collaboration between the hospital and the university.

“Early on, we wanted the center to be built on a foundation bridging two major care needs of families coping with Huntington disease — psychiatric and neurologic,” explains Steven A. Epstein, MD, chair of psychiatry at MedStar Georgetown and professor of psychiatry at Georgetown’s School of Medicine. “The team has done that, and with added additional support services, our center is an exceptional model for Huntington disease centers across the nation. We are proud to have the HDSA designation.”

Clinical research and access to the latest therapies are additional strengths of the center.

“Our center is a clear example of how patients benefit directly from a strong collaboration between a research enterprise, like the medical center, and the hospital,” says Edward Healton, MD, MPH, Georgetown University’s Executive Vice President for Health Sciences and Executive Dean of the medical school. “Our families have access to the latest therapies being studied to treat Huntington disease, in addition to a tremendously experienced support team.”

Recognizing that Huntington’s is a family disease, the Huntington Disease Care, Education and Research Center focuses on providing care for patients and support for their families. As an extension of Georgetown University Medical Center’s dedication to cura personalis — care of the whole person — the center strives to provide cura familia, or care of the whole family.

“All this is possible because of the initial generous gift from the Griffin Foundation to establish the Center,” Anderson says.

"Experts have noted that better patient outcomes are linked to coordinated patient care and clinical research, which can result in better treatments,” Griffin says. “The Huntington Disease Center of Excellence at MedStar Georgetown will help in finding better treatments while delivering needed and better care for patients and families in our region today.”

To learn more about the Huntington Disease Care, Education and Research Center at Georgetown, please call (202) 444-0816 or email [email protected].

MedStar Georgetown University Hospital is a not-for-profit, acute-care teaching and research hospital with 609 beds located in Northwest Washington, D.C. Founded in the Jesuit principle of cura personalis—caring for the whole person—MedStar Georgetown is committed to offering a variety of innovative diagnostic and treatment options within a trusting and compassionate environment.

MedStar Georgetown’s centers of excellence include neurosciences, transplant, cancer and gastroenterology. Along with Magnet® nurses, internationally recognized physicians, advanced research and cutting-edge technologies, MedStar Georgetown’s healthcare professionals have a reputation for medical excellence and leadership.

Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health).  GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person."  The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.

Media Contact

Marianne Worley

Director of Media Relations
Office: 703-558-1287
Pager: 202-405-2824
[email protected]

 

Learn More

Huntington's Disease Center