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Research shows positive effects of CBD in Parkinson’s patients

Parkinson’s disease is a neurodegenerative disease that affects 15,000 Coloradans. From feeling fatigued, depressed and anxious, to experiencing uncontrollable muscle spasms and tremors, symptoms can interrupt every aspect of daily life. Maureen Leehey, MD, has worked with Parkinson’s patients for over 30 years and is looking to the booming world of cannabis for a potential treatment.

‘Let’s do the research’

Leehey, a neurology professor and director of the Movement Disorders Division in the CU School of Medicine, believes cannbidiol, most commonly known as CBD, may provide some relief for patients. CBD is a chemical component of cannabis that has anti-inflammatory properties and does not produce the high associated with marijuana.

“There is a lot of literature that suggests CBD might slow down Parkinson’s disease,” she explained. “This research is in basic science and in animal studies. We really wanted to look at how it could potentially benefit our patients. So we thought let’s do the research.”

‘Jumping through regulatory hoops’

Maureen Leehey
Maureen Leehey, MD, director of the Movement Disorders Division in the CU School of Medicine.

Studying cannabis in a rigorous, scientific manner is incredibly difficult. Due to its schedule I rating from the Drug Enforcement Administration (DEA), a prospective researcher must navigate a complicated regulatory pathway to administer it to study participants. However, this didn’t stop Leehey.

“Once marijuana became legalized recreationally in Colorado, our patients started asking about how it could help them,” she said. “There was a lot of interest, and we wanted to look at how we could help our patients make informed decisions about it.”

After almost two years of attaining compliance to a seemingly endless amount of governing bodies, Leehey’s tenacity paid off.

“We were fortunate in that CU Anschutz provided us with the resources we needed to overcome obstacles and really make this study possible,” she said. A special ventilated room was created for the study participants to consume the marijuana-type study drugs on site, and a storage site for these products was bolted to the ground under the protection of a dual-key lock.

Following regulatory approval, Leehey then received the funds from a grant from the Colorado Department of Public Health and Environment (CDPHE) to start her study.

‘Less irritability and improved nighttime sleep’

Leehey was finally set to administer and monitor the effects of a CBD pharmaceutical on Parkinson’s patients. Thirteen patients entered the study and each was given approximately 400 mg of CBD to start; dosing was increased as appropriate.

Overall, the participants reported they felt less irritable and that they were sleeping better, Leehey said. They even saw that some of their motor symptoms, including stiffness and slowness, improved.

Although the participants experienced some mild side effects, the benefits were clear. These results, along with more anecdotal evidence from her patients outside of the study, encouraged Leehey to run another study. This time, she wants to look at the potential benefits of a small amount of THC combined with CBD in patients with Parkinson’s. She is actively recruiting for this study.

‘Support for other researchers interested in cannabis’

Leehey wants other researchers at CU Anschutz who are interested in cannabis to have support in their endeavors.

“CDPHE gave out a few grants for cannabis research,” she said. “We came together and navigated this research path.”

The awardees have since created a group called the Colorado Cannabis Research Consortium, the C2RC.

“Anyone who is really into cannabis research can be a part of this group,” said Leehey. “A lot of researchers get started and then run into problems. We have been there. We want to use this experience to mentor others and really get this research going.”

If you are interested in participating in Leehey’s study, please contact Ying Liu at 303-724-8288 or ying.3.liu@CUAnschutz.edu.

If you are interested in joining the Colorado Cannabis Research Consortium (C2RC), please contact Kirk Hohsfield at kirk.hohsfield@CUAnschutz.edu.

Guest contributor: Blair Ilsley

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CU Movement Disorders Center named a Center of Excellence

The University of Colorado Movement Disorders Center is now one of now 48 International Centers of Excellence designated by the Parkinson’s Foundation.

CU Motion Disorders Center group photo.
Faculty and staff of the University of Colorado Motion Disorders Center. Center co-directors are Dr. Maureen Leehey, bottom row, far left, and Dr. Lauren Seeberger, bottom row, center.

Designations this year were focused on medical centers that focus on underserved populations. “Other criteria included the ability to provide the highest level of evidence-based patient-centered care, conduct relevant clinical research that serves patient priorities, demonstrate leadership in professional training and conduct impactful patient education and community outreach.”

Here is a link to the Parkinson’s Foundation news release.

The Center of Excellence network is an important part of the Parkinson’s Foundation goal to ensure everyone living with Parkinson’s has access to expert care so they can live better lives. Every center must recertify after five years to ensure the required standards of care.

The center is located within the CU School of Medicine. Dr. Lauren Seeberger and Dr. Maureen Leehey will serve as co-directors of the CU Movement Disorder Center.

Guest contributor: Nicole Leith, Movement Disorders Center Coordinator and Marketing Specialist.

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Research suggests why exercise slows Parkinson’s

Freed and Zhou
Curt Freed, MD, and Wenbo Zhou, PhD

While vigorous exercise on a treadmill has been shown to slow the progression of Parkinson’s disease in patients, the molecular reasons behind it have remained a mystery.

But now scientists at the University of Colorado Anschutz Medical Campus might have an answer.

For the first time in a progressive, age-related mouse model of Parkinson’s, researchers have shown that exercise on a running wheel can stop the accumulation of the neuronal protein alpha-synuclein in brain cells.

The work, published Friday in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate professor of medicine, and Curt Freed, MD, professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.

Exercise in mice boosts protective gene

The researchers said clumps of alpha-synuclein are believed to play a central role in the brain cell death associated with Parkinson’s disease. The mice in the study, like humans, started to get Parkinson’s symptoms in mid-life.  At 12 months of age, running wheels were put in their cages.

“After three months,” Zhou said, “the running animals showed much better movement and cognitive function compared to control transgenic animals, which had locked running wheels.”

Zhou and Freed found that in the running mice, exercise increased brain and muscle expression of a key protective gene called DJ-1.  Those rare humans born with a mutation in their DJ-1 gene are guaranteed to get severe Parkinson’s at a relatively young age.

The researchers tested mice that were missing the DJ-1 gene and discovered that their ability to run had severely declined, suggesting that the DJ-1 protein is required for normal movement.

Study suggests positive human implications

“Our results indicate that exercise may slow the progression of Parkinson’s disease by turning on the protective gene DJ-1 and thereby preventing abnormal protein accumulation in brain,” Freed said.

He explained that his animal experiments had very real implications for humans.

“Our experiments show that exercise can get to the heart of the problem in Parkinson’s disease,” Freed said. “People with Parkinson’s who exercise are likely able to keep their brain cells from dying.”

Parkinson’s is a disease caused by the death of brain cells that make a critical chemical called dopamine.  Without dopamine, voluntary movement is impossible.  Most people with Parkinson’s disease take a drug called L-DOPA to treat their symptoms.  The oral drug is converted into dopamine in the brain allowing patients to get up and move.

In 1988, Freed and his colleague Robert Breeze, MD, performed the first transplant of human fetal dopamine cells into a Parkinson’s patient in the United States. His lab is currently working to convert human embryonic stem cells to dopamine neurons. These techniques should make it possible to produce unlimited quantities of dopamine cells for transplant.

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CU Anschutz hosts student research forum

Why can a rhythmic tune halt the tremors and walking struggles in people with Parkinson’s disease, allowing them to dance with fluidity and box with precision? And why do some teenagers storm sobbing out of clinic doors when their providers broach the subject of weight control?

Those were two of 62 questions University of Colorado Anschutz Medical Campus students tackled as part of the 32nd Annual Student Research Forum. Posters stretched across the north and south towers of the Education 2 building, as the students presented their projects to about 400 of their instructors and peers.

“We’ve been told that the half-life of medical information is approximately seven years, so something that we are taught at the beginning of our first year of medical school may or may not be relevant at the end of our residency,” said David Nguyen, a third-year medical student, explaining the importance of the event. “Especially if we want to go into academic medicine, research is our bread and butter, and we need to stay informed.”

While learning research skills, students also benefit from networking, connecting with mentors, honing presentation skills, boosting resumes and delving into something new by taking part in research forums, said Will Dewispelaere, a second-year medical student. “We all have this inherent scientific desire to find out new things,” he said.

Will Dewispelaere
Will Dewispelaere, a volunteer presenter at the student research forum, studied the effect of rhythm on Parkinson’s patients’ brains.

Probing the Parkinson’s brain

Dewispelaere, whose undergraduate degree is in neuroscience, has had a long interest in disorders such as Parkinson’s disease (PD), a progressive neurodegenerative disease that leads to severe tremors, limb rigidity, slowness of movement and gait and balance problems.

“I’ve been involved with Parkinson’s research since my junior year in college,” he said. “For some time, we have known that if you ask some people with PD to walk, they’ll have trouble getting started. But if you ask them to snap their fingers or listen to music and then walk to the beat, they tend to have fewer problems.”

Research has linked the sound of rhythm to improvement of gait, velocity and postural stability, Dewispelaere said. “Preliminary findings showed music therapy could ease these common Parkinson’s symptoms, including depression and anxiety,” he said, noting the popularity of dancing and boxing classes for PD patients. “But no one really knew why.”

In his study, researchers compared the brains of 23 PD patients with 21 age-matched, healthy patients (HC), using a special imaging technique (magnetoencephalography). The participants tapped a button with their right fingers to rhythmic cues played in their left ears.

While both groups had similar activation in some areas of the brain, the PD group had increased activation in two right areas, one responsible for sound recognition and processing (superior temporal gyri), and the other important to the integration of sensory information, including hearing and self-motion (supramarginal).

“Our conclusion was that increased activity in these two regions of the brain allows for those with Parkinson’s disease to bypass some of their abnormal neural circuitry to generate regular movements,” Dewispelaere said.

Casillas and Vukovic
Paola Casillas and Nemanja Vukovic questioned the quality of weight-control communication between teens and health providers surrounding obesity for their project.

Closing a provider-teenager gap

Four-year medical student Paola Casillas and second-year medical student Nemanja Vukovic focused their project on improving provider and teenage patient communication regarding a top health issue of today: obesity.

“It started about six years ago with a medical student here who saw a lot of these conversations go downhill really quickly, with the teens leaving feeling very discouraged or crying or worse,” Vukovic said. “Feeling like these conversations were super counterproductive, she wanted to know what was turning these kids off,” he said.

With the help of a teenage advisory board, the students devised questions and formed focus groups, using 47 volunteers from Denver-area high schools. The most consistent finding revolved around providers’ use of the Body Mass Index (BMI) chart when initiating conversations about patients’ weight.

Most focus-group members said they disliked the tactic, Casillas said. “They said: ‘I’m not a dot on a screen. This isn’t getting to know me and finding out what I struggle with,” Casillas recounted.

Cultural and gender differences surrounding what family and peers considered appropriate weight also placed pressure on some teens. “The biggest thing we ultimately learned was that they really want the provider to get to know who they are, what their family is like, and their goals and motivations for wanting to lose weight,” Vukovic said.

The project also involved sending surveys to local providers who served teens. Nearly 70 percent of the providers reported almost always starting weight conversations with a BMI chart, with the majority also indicating that their weight-control counseling with teens was not very effective.

The good news: Both providers and teens want to see change. “I was surprised by how much they cared,” Casillas said of the high-school students. “They want to have these conversations with their providers, and they understand the importance of the issue.”

With most providers indicating interest in learning the results of the project and incorporating the findings into their practices, the student researchers aim to expand the study and develop a provider plan for tailoring weight conversations to individual patients, Vukovic said. “We found some areas of disconnect, and we are hoping to bridge those gaps.”

 

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Researchers win National Science Foundation grant to study brain

Researchers from the University of Colorado Anschutz Medical Campus and the University of Colorado Boulder have won an $800,000 grant from the National Science Foundation to try and reconnect neural communication between parts of the brain where it has been severed.

If successful, this could have major implications for those suffering brain injury, stroke, Parkinson’s disease and other neurological problems.

Diego Restrepo, director of the Center for NeuroScience at CU Anschutz.

The team of neuroscientists and engineers will use a special lightweight microscope, which they designed, to peer into and control the living brain of a mouse as they try to reconnect parts of the brain that no longer communicate with each other.

The miniature microscope, using a unique electrowetting lens, is mounted on the head of a mouse and with its high-powered, fiber-optic light can actually view and control neural activity as it happens.

Emily Gibson, assistant professor of bioengineering at CU Anschutz

“Adaptive optical devices that are included in a miniature microscope are a game changer,” said grant co-investigators Juliet Gopinath, assistant professor in electrical, computer and energy engineering and Victor Bright, professor of mechanical engineering, both at CU Boulder.  “They enable truly miniature 3D imaging devices without mechanically moving parts.”

According to Gopinath and Bright, the electrowetting lens is compact, low power and has good optical quality making it ideal for this kind of research. The liquid lens can change shape when voltage is applied.

The team will use an optic fiber to disrupt the signals between the olfactory bulb of a mouse, which receives information on odors, and the olfactory cortex, the part of the brain that allows it to smell. In essence, they will shut down its ability to smell and then try to restore it by activating the olfactory cortex using the miniature microscope.

The mouse will be awake and behaving normally throughout this while the team views and controls what is happening in the brain with the electrowetting fiber-coupled microscope. They can stimulate the animal’s brain activity using powerful laser light that flows through the microscope’s fiber-optic bundle.

“One major problem with the brain is that with certain diseases or injuries, one part of the brain stops talking to another,” said co-investigator Diego Restrepo, professor of cell and developmental biology and director of the Center for NeuroScience at the University of Colorado School of Medicine. “If someone has a stroke they may no longer be able to speak.”

Once connections between brain areas are lost, it is difficult to get them communicating again.

Restrepo said if researchers are successful reestablishing brain connections in a mouse, they may be able do the same in humans with brain injury or disease.

 

“For example, if there is loss of connection between the retina that detects the image in the eyes and the visual cortex, in the back of the brain the patient has a problem detecting images that in the worst case leads to blindness,” Restrepo said.  “That loss of connection between the retina and visual cortex can be due to neural problems such as stroke, neuro-immune disease or traumatic brain injury.”

If this experiment is successful, he said, this microscope could eventually be modified to activate neurons in the visual cortex based on the visual input. In other words, creating a bridge between two parts of the brain where communication has stopped.

“This is an interdisciplinary grant which combines bioengineering with neurological applications,” said Emily Gibson, assistant professor of bioengineering at CU Anschutz. “The idea is to use this device which can image individual neurons and stimulate those individual neurons in that 3D volume.”

She also noted that two of the principal investigators on the grant are women, a rarity in the field of engineering.

“This particular grant is for high risk, high payoff approaches,” she said. “And this is a very high risk project. We are pushing the technology farther and seeing if we can use these optical tools to ultimately make an impact on humans.”

The grant is funded under a program from the National Science Foundation known as the “Integrative Strategies for Understanding Neural and Cognitive Systems (NSF-NCS).”

It is one element of NSF’s broader effort directed at Understanding the Brain, (http://www.nsf.gov/brain/) a multi-year activity that includes NSF’s participation in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

The team also won a second NSF grant of $200,000 to be used in the dissemination and commercialization of its microscope.

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Innovative program puts the punch on Parkinson’s

Power Punch Parkinsons program in Denver

Anthony Mora, left, who was lightweight alternate to the U.S. Boxing Team for the 2000 Olympics, challenges PPP participants to give him their best combination of punches. “I want to make it fun,” he says. “I want to get their confidence up and let them pop off some steam, some stress. I help them believe they can do it.”

With a glint in her eye and clenched jaw, Tina Schoenherr rears back a gloved fist and swings at the target held up by Anthony Mora.

Thuds of fists on punching bags and Mora’s rapid-fire instructions inside the ring – “One-two, Tina! C’mon, one-two!” – fill the basement gym that could easily double as a set for an old-school boxing film, a la “Rocky.” The room pulses with music and motion – mostly middle-aged folks who are strenuously exercising both in and outside the ropes.

It’s another sweat-soaked Saturday of Power Punch Parkinson’s (PPP), but the acronym’s last ‘P’– Parkinson’s – is currently the furthest thing from the participants’ minds.

PPP, a program that gives Parkinson’s patients intensive, non-contact workouts, was co-founded by Mora, former Major League Baseball pitcher Rick Schwartz and Lee Chow, PT, DPT, a 2015 alumnus of the University of Colorado School of Medicine’s Physical Therapy Program. All three men are instructors in the non-profit program, which is sponsored by the Parkinson Association of the Rockies.

While the ground-breaking program they devised may look like boxing, nobody actually gets punched.

CU Anschutz connection

Here at Red Shield Community Center in the Five Points neighborhood, the program is run by Mora and volunteers from the CU and Regis University’s physical therapy programs. Since PPP launched in November 2014, about 100 Parkinson’s patients have participated in the heart of Denver – plus scores more at PPP locations in Boulder, Fort Collins and Colorado Springs – enjoying the fitness and social interaction offered by the weekly classes.

“It’s just been amazing – it’s a fabulous program,” Schoenherr says. “The volunteers from CU and Anthony work with you individually. Now I’ve got stability, I’ve got energy, and my balance is 100 percent better.”

Sammi Stolper of CU Anschutz

Sammi Stolper, left, a second-year physical therapy student at CU Anschutz, assists a participant with a workout station at Power Punch Parkinson’s.

Sammi Stolper, a second-year physical therapy student at CU Anschutz, got hooked on being a volunteer a year ago. “It’s really the people here that keep you coming back,” she says. “You see incredible changes in the participants. They open up, they punch harder and it carries over to hope for them.”

When she graduates, Stolper would like to replicate the PPP model in her home of Arizona, where no similar program exists.

‘A social outlet’

Schwartz, who pitched for the Cleveland Indians from 1968-71, was diagnosed with Parkinson’s 16 years ago. Three years ago, he got the idea that a fitness program centered on boxing – a sport that demands mobility, strength, coordination and balance – could help Parkinson’s patients. He met Mora, a former professional boxer, at the gym one day and then Cheryl Seifert, executive director of the Parkinson Association of the Rockies, connected the two athletes to Chow, who was working on a business-plan project for one of his physical therapy classes at CU.

“There’s nothing like this program in Colorado,” says Chow, now a physical therapist at Platte Valley Medical Center in Brighton. “It gives people with Parkinson’s a social outlet.”

Lee Chow, alumnus of CU Anschutz

Lee Chow, an alumnus of the CU Physical Therapy Program, co-founded the Power Punch Parkinson’s program.

Intense aerobic activity has been found, in animal studies, to release protein compounds that make the brain more “plastic” and better able to resist degeneration, Chow says. “Parkinson’s is a progressive disease,” he says, “so a good outcome is to slow or reach a plateau with your symptoms.”

Participants at the basement gym extol the program for giving them confidence, strength and camaraderie.

‘Treats us as athletes’

Hal Pottle comes to the classes twice a week and loves the adrenalized feel of being a boxer. “Everyone here treats us as athletes, not as someone who has Parkinson’s, which is a pretty high honor,” he says.

Valerie Leonard watches her husband, Bob, go through the various workout stations as a peppy Madonna song blares from the speakers. “There’s a lot of camaraderie here,” she says. “It’s almost like a support group, but instead of sitting and talking, they’re working out together.”

Anthony Mora teaches boxing in Denver

Anthony Mora, right, gives a Power Punch Parkinson’s participant targets to punch at during a recent class in Denver.

Schwartz says the key to PPP’s success – the program has sights to expand to Vail, Grand Junction and Greeley – is the volunteer assistance from the CU Physical Therapy Program. “They’re really dedicated and they make the difference in getting everybody through the system. CU should be proud of them,” he says.

With Parkinson’s, Schwartz says, people aren’t necessarily supposed to get better. But he sees PPP participants gain mental confidence and physical strength all the time. “I’ve seen miracles … I’ve seen people get better, which is the miracle.”

People like Nick Peterson, 65, who learned he had Parkinson’s 41 years ago. “I found out I have a helluva right (hook),” Peterson says with a smile. “This program gives me a feeling of power that I haven’t had in a long time.”

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