Other Things Lewy Bodies Might Do to Our Brains

 NOVEMBER 2, 2018    BY JEAN MELLANO

Pivotal events in my life have piqued my interest in Lewy bodies. The first event was on March 15, 2015, when my life partner, Steve, killed himself. The second was my diagnosis of Parkinson’s disease in November 2015.

My fascination with Lewy bodies (I’ll define them in a bit) began in August 2016 when I watched a documentary called “Autopsy: The Last Hours of Robin Williams.” In this film, forensic pathologist  Richard Shepherd, MD investigated what might have driven Robin to suicide in August 2014. A few months before he died, the beloved comedian and actor had been diagnosed with Parkinson’s.

What might Steve and Robin have in common?

Both Steve and Robin suffered from depression, yet both were supremely talented men with the ability to make so many people happy. To many, it appeared as if they both had lives full of promise ahead of them. According to the documentary, Robin was at a crossroads in his career. Steve also was at a crossroads in his life, trying to sell the business he had built and grown for more than 20 years. The film implied that Robin may have turned to drugs and alcohol to feel better and mask his depression. I believe Steve turned to endurance sports much of his life to accomplish the same. Steve was an 18-time Ironman triathlete finisher, which entails 2.4 miles of swimming, 112 miles of cycling, and 26.2 miles of running.

In my mind, their lives and tragic endings have so much in common.

What are Lewy bodies?

Lewy bodies are abnormal deposits of a protein called alpha-synuclein. These deposits can change how a person feels, thinks, moves, and acts. Lewy bodies can be found in an area of the brain stem where they deplete dopamine, causing Parkinson’s symptoms. There also is a disease called Lewy body dementia, in which these abnormal proteins spread to other areas of the brain. An affected person may become anxious and paranoid. Their decision-making can become impaired. Lewy body dementia can be definitively diagnosed only by a postmortem autopsy.

What was the result of Robin’s autopsy?

According to Shepherd, Robin’s autopsy confirmed the presence of Lewy bodies throughout his brain. Shepherd interviewed the Williams family in an effort to determine Robin’s state of mind prior to his suicide. Robin’s loved ones said he showed signs of paranoia. Shepherd concluded that Robin had undiagnosed Lewy body dementia and that it was this disease that drove him to take his own life.

Steve did not have an autopsy. In many states, if the cause of death is apparent, as it was with Steve, an autopsy is not automatically performed. Steve, like Robin, suffered from depression, and he spiraled downward quickly starting in 2014. A few weeks before he died, Steve expressed to me that he was afraid, but he could not, or would not, articulate why. He was my rock, my Ironman, and he never had been afraid of anything before.

I am not a medical professional, and I wrote this column to inspire conversation about undiagnosed Lewy body dementia as a possible cause of suicide, as Shepherd concluded in the case of Robin Williams.

What can we learn from Robin’s death?

I often wonder if brain autopsies should be routinely performed and analyzed for the presence of Lewy bodies in cases of suicide. Obviously, there are emotional considerations for the families and costs involved, but perhaps the knowledge learned from these autopsies may help others.

Maybe undiagnosed Lewy body dementia is more prevalent than we think, especially when suicide is the obvious cause of death.

If you or anyone you know is experiencing suicidal thoughts or needs someone to talk to, please call the National Suicide Prevention Line at 800-273-8255 or visit suicidepreventionlifeline.org.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/11/02/parkinsons-lewy-bodies-dementia-suicide-robin-williams/

The Grouch and T.O.O.T.S.: Dealing with Irritability

NOVEMBER 2, 2018 DR. C'S JOURNEY WITH PD 

Years ago when I was first diagnosed, my partner asked the neurologist, “Is there something we can do about his irritability?” The doctor responded, “I wish I had a dollar for every time a partner made this request.”

It seems this is a prevalent issue. In past columns I have addressed scenario looping breakdowns, exaggerated emotions, deep fatigue, bad days, and ugly days. All of these contribute to the occurrence of irritability. Add to this “off-periods,” which also increase irritability.

The grouch rears its growling snout, and to keep the relationship protected, T.O.O.T.S. is the necessary muzzle. T.O.O.T.S. stands for Time Out On The Spot. It means that you “time yourself out” — zip the lip and take a trip. Walk away and return when calmer moods prevail.

As a therapist and professor, I have lots of practice monitoring my internal emotive state and taking actions to prevent it from affecting my ability to help others. But with Parkinson’s, it became more difficult. The first time the grouch barked back to a student in class and “put her in her place,” it happened on one of those bad days that overlapped with high irritability. But it was a shock to me that it happened, and I went to the department chair to explain it. He shrugged it off.

I told my neurologist that it was as if the normal filters I use to screen my emotions were not working properly. The emotions just spilled out and this grouch took over. Now further along with the disease, not a day goes by when I don’t have to muzzle the grouch.

PD irritability can bring other exaggerated emotions. Every little thing becomes blown out of proportion. Example: I’ve asked my partner not to smoke in the house and even hung a no-smoking sign. (Yes, inside the house!) Yet, a cigarette still gets lit indoors prior to my partner walking outside. The smoke makes me nauseous and triggers the grouch.

How many little things occur in a relationship that are annoying? With the grouch, it is not like a-fly-in-the-room annoying, but more like someone stole-your-lunch-money annoying. Smelling smoke in the house after numerous reminders is sickening and close to infuriating. I put T.O.O.T.S. into action, calmed down, and later planted a gentle reminder — again. Doing it this way prevents an argument or fight and saves the quality of the relationship. Zip the lip — save the relationship.

Dealing with the irritable grouch not only requires T.O.O.T.S., but also the following

– The 1-to-10 rating system of how bad the day is, which can be a grouch warning.

– Exercise, which can decrease grouch problems.

– Realizing that deep fatigue, if not attended to, will increase grouch problems.

– Understanding that ruminating on something annoying makes it worse; the key is to find a way to move past it.

– Telling people what you want from them. If you wait for them to read your mind, you will be disappointed — and annoyed.

Stress, lack of sleep, not eating or hydrating properly, and disruptions in the daily routine all can act as triggers for the grouch. Self-monitoring all of this as a way of keeping the grouch muzzled is not something that happens with perfection. The grouch still barks at family and partner, but the rehab plan decreases the frequency.

Even more than that, the plan gives reassurance to those who love you that you are doing all you can. Zip the lip — save the relationship.

Does the grouch arrive at your home?

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/11/02/parkinsons-disease-grouch-toots-dealing-irritability-stress/

Benefits of Exercise for Parkinson’s Patients Linked to Increased Dopamine Release, Study Suggests

NOVEMBER 2, 2018 BY PATRICIA INACIO, PHD IN NEWS.

Engaging in regular exercise can help preserve the motor and non-motor function of Parkinson’s disease patients, most likely as a result of an increased release of dopamine in the brain, a small study suggests.

The study, “Habitual Exercisers Versus Sedentary Subjects With Parkinson’s Disease: Multimodal PET and fMRI Study,” was published in the journal Movement Disorders.

Exercise has been shown to ease both motor and non-motor symptoms of Parkinson’s disease, including bradykinesia (slowness of movement) and balance, as well as cognition and mood.

While the mechanisms underlying these benefits are largely unknown, researchers hypothesize that exercise may enhance dopamine release. The progressive degeneration and death of nerve cells in the brain that produce dopamine, called dopaminergic neurons, is one of the underlying causes of Parkinson’s disease.

In this study, researchers investigated how dopamine release and other clinical features of Parkinson’s disease differ between patients who exercise and those who remain sedentary.

A total of 17 patients with mild to moderate Parkinson’s disease were recruited, eight of whom engaged in regular exercise at least three times a week for more than three hours total, while nine were sedentary.

All patients underwent two positron emission tomography (PET) scans, one before and one after exercising on a stationary cycle, to determine whether exercise affects the release of natural dopamine in the dorsal striatum — a region of the brain involved in the control of movement. PET scans were performed after overnight withdrawal from dopaminergic medication.

Additionally, participants underwent functional magnetic resonance imaging (MRI) of the brain during a monetary reward task that required randomly selecting one of four cards.

“Subjects were explicitly informed about the probability of obtaining a monetary reward ($0.50) for selecting a winning card during each block. Subjects were also instructed that the task was purely chance (analogous to a slot machine), and there was no pattern to learn that could improve odds,” the researchers wrote.

However, for each selected card, subjects were provided visual (happy or sad face) and auditory (cheers or sighs) feedback, which could alter the card selection process, even though the success of each trial was by chance.

This test allowed researchers to evaluate possible behavioral differences in card selection between groups. Specifically, researchers measured the response of the brain’s ventral striatum, a region involved in the evaluation of rewards.

Participants also completed other tests to evaluate motor and non-motor function, including the Beck Depression Inventory to assess depression and the Starkstein Apathy Scale to measure apathy.

Results showed that habitual exercisers had an increased release of dopamine compared with sedentary patients. They also had greater activation of ventral striatum during the MRI reward task. Their apathy and bradykinesia scores were also lower than sedentary patients.

These results suggest that exercise is associated with improved motor and non-motor functions in Parkinson’s patients, which is likely linked to exercise-enhanced dopamine release.

“Although it appears that exercise plays a role in the clinical outcome of subjects with PD, future randomized control trials are needed to determine the cause-effect relationship between exercise and enhanced DA [dopamine] release, response to anticipation of reward, and clinical outcomes,” the researchers wrote.

“Future studies should also investigate other potential mechanisms of benefit from exercise,” they added.

https://parkinsonsnewstoday.com/2018/11/02/exercise-benefits-parkinsons-linked-dopamine-release-study/

Singing helps Communication and Confidence

Thursday, 1 November 2018    Therapy Professionals

The Cantabrainers Choir is a choir for people with neurological conditions, such as Stroke and Parkinson’s Disease. Its purpose is not so much to create sweet music, but to provide a safe environment in which members can rediscover their voice through singing and socialising.

Established by Therapy Professionals Ltd in 2012, with a small grant from Music Therapy NZ, it was a perfect fit for this private community practice of Therapists, who since 1985 have worked with people of all ages with disabilities. 

The Choir differs from other community choirs in that you don’t have to be a ‘singer’; it’s about learning to use the voice effectively, in a fun way; it suits a wide range of abilities; the pace is slower; the repertoire is chosen to target specific difficulties; it’s not as challenging; and practice is in the morning when people are fresh.

The limited ability to communicate can lead to social isolation and depression. As our voice comprises about 38% of our communication, it is not surprising it can be badly affected by many neurological conditions. For example, in Parkinson’s disease, 90% of people have difficulty with speech or voice; the voice may become very quiet, rapid, flat and monotonous. 

Following a stroke, one in three have difficulty communicating. They may experience complete or partial inability to form spoken words; lack of muscle coordination making words sound slurred and incomprehensible; and problems with speech due to memory impairment or word finding difficulties. 

The rationale behind the choir can be found in research, which shows after trauma the brain may recover some abilities, given effort and the right stimulation. Like getting fit, rewiring the brain or neural plasticity requires intensive exercise to be done accurately and regularly. 

Also choral singing releases chemicals responsible for happiness; relaxation; connection; boosting our immune system; helping us handle pain. Unlike speech, music activates a number of areas on both sides of the brain. If one area is damaged then another can compensate, given the right stimulation.

Music and speech share many characteristics: pitch, pace, rhythm, tone and volume, which is why the Cantabrainers Choir is run by Music and Speech Language Therapists.

The Music Therapist’s expertise is in using music and singing to promote positive change with the voice. She arranges the music, leads and accompanies the choir. 

The Speech Language Therapist’s expertise is in understanding the relationship between disability and how it affects our voice and strategies to compensate.

During the session she focuses on individuals, by using exaggerated modeling, while repetitive songs give immediate practice.

The choir’s effectiveness has been measured through initial outcome measures, research and satisfaction surveys. All show an improvement in the voice, confidence and happiness of the members. Anecdotally members express improved confidence and engagement in life. To quote a choir member 

Lois James, “The music has been a real uplift and meeting new people has been wonderful and so much fun. I have a lot more confidence than I had. It’s got me out of my cage”.

Therapy Professionals has largely funded the choir with help from the $10 fee per session, concerts, raffles and some grants and donations. Evan under the auspices of the New Zealand Brain Research Institute the choir couldn’t raise enough funds to cover the choir’s running cost.

Therapy Professionals is pleased to announce “The Cantabrainers Therapeutic Choir Charitable Trust”, established this year, will take over the running of the choir form the beginning of 2019.

The choir runs 10 - 11.45 am every Wednesday in school terms at Mary Potter Community Centre, 442 Durham Street North. All are welcome to come along either to view or join. 

http://www.scoop.co.nz/stories/GE1811/S00001/singing-helps-communication-and-confidence.htm

Phase 2 Trial Testing Anavex 2-73 Recruiting Parkinson’s Patients With Dementia in Spain

 NOVEMBER 1, 2018 BY ALICE MELÃO

The first patient has been enrolled in Anavex Life Sciences‘ Phase 2 clinical trial to evaluate the potential and safety of Anavex 2-73 as a treatment for Parkinson’s disease dementia.

Now actively recruiting, the study (2017-004335-36) is expected to enroll approximately 120 Parkinson’s patients ages 50 or older with a dementia diagnosis. It is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.

Anavex has been developing Anavex 2-73 as a potential disease-modifying therapy for Alzheimer’s disease. It is a small molecule that activates the sigma-1 receptor located in a cellular structure called the endoplasmic reticulum, which is critical for several cellular regulatory mechanisms.

“We are very pleased to initiate our first patient enrollment into the Parkinson’s disease dementia Phase 2 study of Anavex 2-73,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release. “This is an important step toward achieving clinical data for the second indication initiating this year for Anavex 2-73 also incorporating genomic precision medicine biomarkers.”

Trial participants will be randomly assigned to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks.

Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as on patients’ motor function and sleep quality.

During the study, researchers will also assess genomic precision medicine biomarkers associated with Anavex 2-73 that were identified in another Phase 2 trial (NCT02244541) in Alzheimer’s disease.

Additional information (in Spanish) on the trial can be found here. Patients and caregivers interested in taking part in the study can download and fill out a simple screening questionnaire that is available on the website to assist in discussions with their physician.

“Parkinson’s disease is an already prevalent disease among older individuals that is poised to become a much greater public health problem around the globe in the coming decades and is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes,” Jaime Kulisevsky, MD, PhD, principle investigator of the Phase 2 trial, as well as a professor at the Autonomous University of Barcelona and director of the Movement Disorders Unit of the Sant Pau Hospital in Barcelona.

Results from preclinical studies have shown that Anavex 2-73 has the potential to restore function to damaged nerve cells in mouse models of Parkinson’s disease. The compound was also found to target faulty proteins and poorly working mitochondria — the cells’ powerhouses — preventing oxidative stress and inflammation.

As of now, only one medication, Nuplazid (pimavanserin) is approved by the U.S. Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/11/01/anavex-recruiting-parkinsons-dementia-patients-spain-anavex-2-73-trial/

Middle-Onset Parkinson’s Linked to Impaired Ability to Detect Emotions, Study Finds

NOVEMBER 1, 2018 BY MARTA FIGUEIREDO 

Patients with middle-onset Parkinson’s disease have difficulties recognizing negative and neutral emotions, deficits that appear to be even stronger in female patients, a study shows.

The study, “Emotion-Specific Affective Theory of Mind Impairment in Parkinson’s Disease,” was published in the journal Scientific Reports.

Parkinson’s disease is known to affect the frontal-subcortical circuit, an area responsible for motor and behavioral processes.

This region is also responsible for processing the theory of mind (ToM), a complex function that enables the detection and recognition of cognitive and emotional states (thoughts, feelings, beliefs, intentions, or desires) of other people, and thus the anticipation and interpretation of their behaviors. These abilities are crucial in a social situation for successful communication.

ToM can be divided into cognitive ToM, involved in reading the cognitive beliefs of other people, and affective ToM, involved in recognizing and interpreting the emotional states of others.

While Parkinson’s disease is known to impair cognitive ToM, whether it influences affective ToM remains controversial, with several studies reaching varying conclusions.

Researchers in Taiwan evaluated whether affective ToM is affected in Parkinson’s patients with either young-onset (YOPD) or middle-onset (MOPD) disease, and whether impaired affective ToM is associated with Parkinson’s motor symptoms.

Researchers first recruited 30 people with middle-onset Parkinson’s, 30 young-onset Parkinson’s patients, and 30 healthy participants. Young-onset was defined as developing the disease at 49 years of age or younger, while middle-onset was classified as developing the disease between 50 and 70 years old.

Affective ToM was assessed through the validated Reading the Mind in the Eyes Test (RMET), which comprises 36 black-and-white photographs of pairs of eyes that each depict a particular emotion. These photographs are shown to the participant, who must pick the adjective that best fits the emotion.

Results showed that while young-onset Parkinson’s patients and healthy individuals appeared to have comparable abilities to infer emotions in others (similar RMET scores), patients with middle-onset Parkinson’s had significant difficulties recognizing emotions — particularly negative and neutral emotions.

Researchers also found that these deficits were only present in women in the middle-onset group.

“This finding may imply that female patients with MOPD have a vulnerable emotional recognition ability; thus, early detection and appropriate treatment are needed for the female MOPD population,” the researchers wrote.

They noted that these results may explain the variability of previous studies, since Parkinson’s patients with particular disease onsets or genders showed distinct differences in affective ToM.

Next, the team analyzed the data of 107 middle-onset Parkinson’s patients, which included the initial 30 patients, plus an additional 77 participants, to better understand the potential associations between deficits in affective ToM and Parkinson’s motor and non-motor symptoms in these patients.

In this Parkinson’s population, the ability to accurately interpret the emotional state of others decreased with disease duration and with the presence of specific motor symptoms, such as slowness of movement, walking and posture instability, and impaired speech and facial expression.

Additional analysis showed that impaired ability to recognize others’ emotions in these patients was associated with the development of motor symptoms, but not of non-motor symptoms. The same was true for women in this group of patients.

The team noted that the data support an association between affective ToM and motor symptoms, and that additional studies are required to clarify the underlying mechanisms of this link, and to more thoroughly evaluate the potential link between affective ToM and cognitive function.

They also believe the use of a test with both verbal and nonverbal information to assess affective ToM may “provide more comprehensive context that mimics real-life situations.”

“Whether the affective ToM can be used as a biomarker to detect or diagnose PD [Parkinson’s disease] is a noteworthy issue, and the development of a useful diagnostic tool is therefore needed,” they concluded.

https://parkinsonsnewstoday.com/2018/11/01/middle-onset-parkinsons-disease-linked-impaired-detection-emotions-study/

Road to cell death more clearly identified for Parkinson's disease

November 1, 2018, Johns Hopkins University School of Medicine

Dopamine neurons are the primary cell type targeted by Parthanatos in Parkinson's disease. Credit: The Dawson Lab

In experiments performed in mice, Johns Hopkins researchers report they have identified the cascade of cell death events leading to the physical and intellectual degeneration associated with Parkinson's disease.

Results of the study, published Nov. 2 in Science, suggest promising new targets for drugs that could interrupt Parkinson's disease progression.

The study, the researchers say, focused on Parthanatos, a specialized "programmed" pathway toward cellular death named for Thanatos, the ancient Greek personification of death, as a key driver of nerve cell degradation that is a marker of Parkinson's disease. It is distinct from other known forms of programmed cell death such as apoptosis (a normal part of growth and development) and necroptosis (generally cell death due to disease or injury). 

The first step down Parthanatos in Parkinson's disease is the accumulation of misfolded proteins in brain neurons. These proteins, known as alpha synuclein, have long been linked to Parkinson's disease progression, but it was unclear how they specifically affected brain cells.

"Nailing down how cells die in this disease increases our hope that someday we will be able to treat and possibly cure Parkinson's disease," says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

To find out more about which "road" to cell death Parkinson's cells travel, the research team treated lab-grown mouse brain cells with preformed clumps of alpha synuclein and observed their response over the course of 14 days. As the brain cells began to die off, the researchers observed that they had "turned on" a protein called PARP1, a gateway to cell death via Parthanatos.

They then tested whether blocking PARP1 could rescue the cells from certain death. In an additional experiment, the researchers again added alpha synuclein clumps to healthy mouse brain cells and then treated the cells with one of three drugs that block PARP1's function: veliparib (ABT-888), rucaparib (AG-014699) or talazoparib (BMN 673), all currently used by oncologists to treat breast and ovarian cancers. The researchers found that the cells treated with these drugs were protected from death at 14 days.

To test this principle in living mammals, the research team injected alpha synuclein clumps into the brains of normal mice and mice genetically engineered to lack the PARP gene. The researchers found that the normal mice began to show muscle weakness, loss of coordination and decreased movement, as seen in tests of the mice's grip strength and the ability to climb down a vertical pole, three months after treatment. However, both the mice lacking PARP and normal mice treated with PARP blockers showed no decline.

"Showing that blocking this key step in the Parthanatos pathway protected the cells against death is evidence that Parkinson's disease kills cells through this mechanism," says Tae-In Kam, Ph.D., lead author on the study and postdoctoral fellow in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.

Past studies showed that PARP causes neurons to create a sugar called PAR, which binds to alpha synuclein and increases the rate at which the alpha synuclein proteins clump together. Kam wondered whether the increase in PARP1 he observed in Parkinson's cells could be causing a similar effect.

To test this hypothesis, the researchers added PAR along with the preformed alpha synuclein clumps to lab-grown mouse brain cells. They found that the combination of PAR and alpha synuclein formed a different, more neurotoxic strain of the alpha synuclein clump. The cells treated with this combination died off 25 times faster than their counterparts receiving alpha synuclein alone.

To validate this observation, the research team repeated the experiment in normal mice. The researchers administered the preformed alpha synuclein clumps or the more toxic PAR/alpha synuclein combination to the mice's brains and again observed them for six months. The mice who received only alpha synuclein clumps began to show signs of degeneration six months after treatment.

 However, the mice that received the combination treatment experienced degeneration twice as fast, exhibiting significant degeneration at just three months.

"The PAR/alpha synuclein combination is not only faster at killing neurons, it's a more potent toxin," says Kam.

To gauge whether this mechanism could be in play in human Parkinson's disease, the researchers collected cerebrospinal fluid from 21 Parkinson's disease patients in various stages of the disease, and fluid samples from 33 healthy people. The team then measured the amount of PAR in each sample. What they found was that there was approximately twice the amount of PAR in the samples from people with Parkinson's disease.

"Additionally, one out of four of our samples showed a correlation between PAR concentration and the disease's progression," says Kam.

The researchers emphasized that much more research needs to be done before their findings can be applied to humans, but if further experiments support their results, the researchers hope to work on clinical trials with drug companies that currently produce drugs targeting PARP to test the ability of these drugs to slow, or even stop, Parkinson's disease in humans.

"If PARP inhibitors work in human Parkinson's disease patients as they have in mice, they could be protective of cells already affected by Parkinson's disease, but also slow the transmission of these harmful proteins to new cells," says Valina Dawson, Ph.D., professor of neurology at the Johns Hopkins University School of Medicine.

Parkinson's disease is a progressive disorder of the nervous system that affects approximately 1 million people in the U.S., according to the Parkinson's Foundation. Early symptoms include tremors, trouble sleeping, constipation and trouble moving or walking, which ultimately give way to more severe symptoms such as loss of motor function and the ability to speak, and dementia. Most people begin showing symptoms in their 60s, but cases have been reported in patients as young as 2 years old.

More information: "Poly(ADP-ribose) drives pathologic a-synuclein neurodegeneration in Parkinson's disease" Science (2018). science.sciencemag.org/cgi/doi … 1126/science.aat8407

Journal reference: Science

Provided by: Johns Hopkins University School of Medicine 

https://medicalxpress.com/news/2018-11-road-cell-death-parkinson-disease.html

Twenty years on, measuring the impact of human stem cells

November 1, 2018 by Terry Devitt, University of Wisconsin-Madison

In November 1998, the world was introduced to human embryonic stem cells, the blank slate cells that arise at the earliest stages of development and that go on to become any of the scores of cell types that make up a human.

In a succinct paper published in the journal Science and heralded around the world, University of Wisconsin-Madison developmental biologist James Thomson described the first successful derivation and culturing of the master cells of life. With a capacity to replicate endlessly under the right laboratory conditions, the prospect of an inexhaustible supply of replacement cells for ailments such as Parkinson's, diabetes, heart disease, spinal cord injury and a host of other dire conditions catapulted the cells into the biomedical spotlight and the public imagination.

"When human embryonic stem cells were discovered 20 years ago, researchers and the public were quick to realize the tantalizing promise that these cells provided for therapeutic applications," notes Tim Kamp, a professor of medicine in the UW School of Medicine and Public Health and the director of the University of Wisconsin-Madison's Stem Cell and Regenerative Medicine Center. "There was now a potential pathway to generate essentially any human cell type in the body in the laboratory and then use it to replace damaged or destroyed cells by disease such as beta cells in the pancreas in diabetes, dopaminergic neurons in Parkinson's disease, and heart muscle cells after a heart attack."

Beginning with just five cell lines derived from surplus embryos donated by patients who had finished undergoing fertility treatments, human stem cell science has mushroomed from just a few isolated labs to a burgeoning global industry and launched the new field of regenerative medicine.

Today, proven therapies based on trading out diseased cells for healthy lab grown cells remains a clinical aspiration. But a growing number of clinical trials, the widespread use of the cells in industry, and a swelling list of basic findings attributable to the Swiss Army knife of cells is contributing to a measured, steady realization of the promise that came with the first lab-grown cells two decades ago.

"What is surprising is how far we've come and how fast we've gotten there," says Tenneille Ludwig, director of the Stem Cell Bank at WiCell, a non-profit affiliate of UW-Madison that studies, distributes and characterizes stem cells for research. Ludwig is the senior author of a paper published today (Nov. 1, 2018) in the journal Cell Stem Cell describing the global scope and economic impact of stem cell science, including the clinical, industrial and research use of the cells.

Not surprisingly, the potential of clinical applications for stem cells has garnered the most attention over time, and while unproven treatments to treat everything from arthritis to Alzheimer's have surfaced in clinics in the United States and abroad, there has yet to be an effective stem cell treatment that has successfully navigated the gamut of clinical trials required for FDA approval.

"If you're looking for a proven embryonic or induced stem cell therapy, there isn't one quite yet," Ludwig explains, noting the timeline from the lab to the clinic is seldom speedy or direct. "We know it takes a long time to go from a basic scientific discovery to the clinic."

Ludwig, who worked as a post-doctoral fellow in Thomson's lab developing and refining the culture media required to grow and nurture the cells in the lab dish, says her survey of the field reveals 29 clinical trials in 10 countries. Twenty-seven of those trials involve cells derived from human embryonic stem cell lines, including some of the original stem cell lines derived in 1998. "We expect the number of clinical trials to balloon over the next five to ten years."

Less publicized is the use of stem cells to develop high-throughput drug screens. Nearly every major pharmaceutical company now has a stem cell program where the cells are used to assess promising new drug candidates for safety and efficacy.

Also flying under the public's radar is the growing scientific contribution of stem cells, both embryonic and induced pluripotent cells. (Induced pluripotent cells are adult cells such as skin that have been genetically reprogrammed to mimic the qualities of embryonic stem cells.) Although the science for embryonic stem cells was slowed by early controversies and limited funding during the Bush administration, the field has taken off as public funding has become more readily available and now nearly 400 embryonic stem cell lines are eligible for public funding through the National Institutes of Health (NIH) Stem Cell Registry.

Drawing on data from NIH, Ludwig and her study co-authors, estimate as much as $1.43 billion has been spent by the agency on research on embryonic and induced stem cells over the past 20 years.

As a result of greater access to stem cell lines and more robust public funding, the science of stem cells has advanced significantly. Scientists, for example, are able to direct the blank slate cells to become many of the cells found in the body. From beating heart cells and insulin-producing beta cells to motor and dopaminergic neurons, scientists are making large quantities of pure cells for research, in many cases creating cells that could not otherwise be accessed for science.

"In the first several years, there were only about 80 papers in the whole field," notes Ludwig. "Now, twenty years in, there are tens of thousands. It is pretty remarkable."

Says Kamp: "Now, after 20 years of ongoing research and development, we are seeing clinical trials emerging that are testing cellular products derived from embryonic stem cells for a variety of diseases including diabetes, ischemic heart disease, age-related macular degeneration, and more. Most of these trials are just the beginning safety studies, but the remarkable new regenerative medicine applications of human embryonic stem cells and their more recent cousins induced pluripotent stem cells are beginning to realize the promise for revolutionary new therapies first identified 20 years ago."

Journal reference: Science     Cell Stem Cell 

Provided by: University of Wisconsin-Madison

https://medicalxpress.com/news/2018-11-twenty-years-impact-human-stem.html