Parkinson's study patients reach 42 weeks post NTCELL implant

10/27/2015 |

In all four patients NTCELL treatment has stopped the progression of Parkinson’s disease as measured by globally accepted and validated neurological rating scales.

In all four patients the 42 week post-implant data show there is a clinically and statistically significant improvement in the patients’ neurological score from their pre-implant baseline. That improvement is equivalent to approximately 5 years of Parkinson’s disease remission and is maintained 74 weeks after NTCELL transplant in the first patient.

Data from the ongoing monitoring of the four patients was measured by validated neurological rating scales and questionnaires, including the Unified Parkinson’s Disease Rating Scale (UPDRS), the Unified Dyskinesia Rating Scale (UDysRS) and the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39). These scales and questionnaires are used to assess improvements in patients’ movement abnormalities, other physical symptoms, well-being and ability to perform everyday tasks.

Dr Ken Taylor, Chief Executive, says the continued improvement of the patients is pleasing.

“We are delighted with the continued positive outcome of the study to date. It certainly adds anticipation and motivation to the planned Phase IIb study. The Phase IIb study will confirm the effective dose of NTCELL, define any placebo component of the response and further identify the Parkinson’s disease patient sub group we would initially target.”

http://health.einnews.com/article/293664031/ckkx6lDGYRvT31WR

8 Things Every Parkinson’s Disease Caregiver Should Know October 26, 2015

October 26, 2015

If someone you love has been diagnosed with Parkinson’s disease, the best thing you can do — for yourself and for your loved one — is to get educated.

Feeling overwhelmed and confused by a Parkinson’s disease diagnosis is not only common for the person with the disease, but also for the primary caretaker. To help build your understanding, we asked experts who treat Parkinson’s every day: What should caregivers know about Parkinson’s disease? Here are their top eight frequently asked questions:

1. What is Parkinson’s disease? Parkinson’s is a progressive disorder that affects the nervous system and leads to problems with movement that worsen over time. “Parkinson’s disease results from a loss of cells in the brain that make dopamine, which is a critical chemical for coordinating movement,” says Ariane Park, MD, a neurologist at Ohio State University’s Wexner Medical Center who specializes in treating people with movement disorders, including Parkinson’s.

2. What causes Parkinson’s disease? Scientists aren’t sure exactly what causes Parkinson’s, but they have identified a couple of factors that may play a role: genetics and the environment, or a combination of both.

Most of the time, the disease occurs sporadically, meaning no other family members are affected. However, “a small group of patients do have familial Parkinson’s disease, which is caused by a mutation in one of their genes,” says Eugene Lai, MD, a neurologist with Houston Methodist Neurological Institute who specializes in neurodegenerative diseases.

Researchers are also studying whether environmental toxins, such as pesticides, may play a role, according to the National Institutes of Health (NIH), though the risk is believed to be small.

The biggest known risk factor for Parkinson’s? Aging. The majority of people who start to develop Parkinson’s disease are 60 or older.

3. What are the common symptoms of Parkinson’s disease? “Most people think there must be tremors for it to be Parkinson’s disease, but that’s not always the case,” says Adena Leder, DO, a neurologist with the Adele Smithers Parkinson’s Disease Treatment Center at NYIT College of Osteopathic Medicine in Old Westbury, New York. While each patient’s experience is unique, the most common Parkinson’s symptoms include:

• Tremors
• Slowness and stiffness
• Memory difficulties
• Mood changes
• Swallowing issues
• Balance problems
• Sleep difficulties
• Erratic changes in blood pressure

Other symptoms may include constipation, fatigue, rapid eye movement (REM) sleep behavior disorder, depression, and anxiety.

Sometimes, the earliest Parkinson’s symptoms can show up more than a decade before a diagnosis, Dr. Leder says. Those may include a loss of sense of smell and acting out dreams during sleep.

4. How will Parkinson’s disease progress? Because Parkinson’s is neurodegenerative, symptoms get worse over time. “The progression varies from person to person, and we unfortunately have no way of knowing how fast or slowly a person will progress,” Dr. Park says. Leder notes that progression can occur over two decades or as quickly as within two or three years

People with Parkinson’s need not feel helpless when it comes to how their condition will develop, however. “Patients who are more active — and are engaged in meaningful exercise, including physical therapy — tend to progress more slowly and have a better quality of life,” Leder says.

5. What Parkinson’s disease treatments are available? “Although there is no cure for Parkinson’s disease, it’s important to know that it is a treatable condition,” Dr. Lai says. “There are many treatments for Parkinson’s disease, and they can be divided into pharmacological, non-pharmacological, and surgical.”

Physicians usually try to treat Parkinson’s with medications first, specifically those that increase dopamine in the brain.

“Non-drug treatments include physical therapy, daily exercise, adequate rest, balanced diet, and socialization,” Lai says.

In more advanced disease, when medications are not controlling the symptoms well, a form of surgery called deep brain stimulation may be an option.

6. What can I do as a caregiver to help my loved one? You can’t stop the condition, but you can facilitate some parts of treatment. You can encourage your loved one to exercise regularly, sleep well, and stay hydrated, says Park.

“Caregivers also play a critical role in observing mood and can provide important insight into the patient as a whole, helping the physician to best tailor care,” she adds.

7. What are some warning signs that Parkinson’s disease is progressing? “If a person has increased difficulty with swallowing, that can indicate the disease is progressing,” Leder says. “It may also indicate that there needs to be a dietary change.”

A decline in gait can also signal the disease is getting worse. “If the person isn’t already in physical therapy,” she says, “this is a good time to start.”

8. What can I do to avoid caregiver burnout? Parkinson’s disease is a chronic illness, and the burden on caregivers can be overwhelming. “As a caregiver, it’s important to have good insight and regularly evaluate your physical, financial, and emotional strain before you experience burnout,” Park says. It’s also important to have an aide or another family member who can offer you periodic “time off.”

Your physician or a clinical social worker can offer additional suggestions and resources to help you as a caregiver. You can also find support through local support groups and chapters of the National Parkinson Foundation.

http://healthcaresolutionsplus.org/8-things-every-parkinsons-disease-caregiver-should-know/

Brain surgery live: Meet the patient, Greg Grindley

OCTOBER 25, 2015

WASHINGTON —An Ohio man will undergo brain surgery Sunday night – live on national television.

Brain Surgery Live with Mental Floss will air Sunday at 9 p.m. on the National Geographic Channel. It’s the first time for a brain surgery to be broadcast live in the U.S.

The patient is a 49-year-old Ohio electrician named Greg Grindley. The procedure, known as deep brain stimulation, is intended to ease the symptoms of Parkinson’s disease, which freezes his face and makes his hands tremble.

Grindley will be awake during the surgery, and his reactions will help guide the surgeons as they thread four electrodes deep into his brain.

The doctors involved say the surgery is a common one, and televising it won’t pose any extra risk.

They say it will help raise awareness about the procedure and hopefully help patients who are suffering.

Doctors will answer questions from viewers during the broadcast.

You can join in on the discussion using the hashtag #brainsurgerylive on Twitter.

http://healthpassion.info/parkinsons-brain-surgery-to-broadcast-on-live-t-v/

Gene therapy prevents neuronal death, disease effects in experimental model of PD

October 9, 2015

An estimated seven to ten million people worldwide are living with Parkinson's disease (PD), which is an incurable and progressive disease of the nervous system affecting movement and cognitive function. More than half of PD patients develop progressive disease showing signs of dementia similar to Alzheimer's disease. A research team at University of Copenhagen, Denmark, has discovered that non-inheritable PD may be caused by functional changes in the immune regulating gene Interferon-beta (IFNβ). Treatment with IFNβ-gene therapy successfully prevented neuronal death and disease effects in an experimental model of PD. The results have just been published in prestigious scientific journal Cell.

Protein regulates waste management in nerve cells

The human brain consists of approximately 100 billion neurons, which coordinate activities in all parts of the body. At Biotech Research and Innovation Centre (BRIC), University of Copenhagen, the group of Professor Shohreh Issazadeh-Navikas has discovered that the immune gene IFNβ plays a vital role in keeping neurons healthy.

this, the waste proteins accumulate in disease-associated structures called Lewy bodies and with time the neurons die, explains assistant professor Patrick Ejlerskov, the first author of this report.

The research team found that mice missing IFNβ developed Lewy bodies in parts of the brain, which control body movement and restoration of memory, and as a result they developed disease and clinical signs similar to patients with PD and dementia with Lewy bodies (DLB).

New understanding of non-familial Parkinson's disease 

While hereditary gene mutations have long been known to play a role in familial PD, the study from BRIC offers one of the first models for so-called non-familial PD, which comprises the majority (90-95%) of patients suffering from PD. According to professor Shohreh Issazadeh-Navikas the new knowledge opens new therapeutic possibilities:

-This is one of the first genes found to cause pathology and clinical features of non-familial PD and DLB, through accumulation of disease-causing proteins. It is independent of gene mutations known from familial PD and when we introduced IFNβ-gene therapy, we could prevent neuronal death and disease development. Our hope is that this knowledge will enable development of more effective treatment of PD, says professor Shohreh Issazadeh-Navikas.

Current treatments are effective at improving the early motor symptoms of the disease, however, as the disease progress, the treatment effect is lost. The next step for the research team will be to gain a better understanding of the molecular mechanisms by which IFN? protects neurons and thereby prevents movement disorders and dementia.

http://www.news-medical.net/news/20151009/Gene-therapy-prevents-neuronal-death-disease-effects-in-experimental-model-of-PD.aspx

Scientists can now use skin samples from older patients to grow brain cells

 October 9, 2015

For the first time, scientists can use skin samples from older patients to create brain cells without rolling back the youthfulness clock in the cells first. The new technique, which yields cells resembling those found in older people's brains, will be a boon to scientists studying age-related diseases like Alzheimer's and Parkinson's.

"This lets us keep age-related signatures in the cells so that we can more easily study the effects of aging on the brain," says Rusty Gage, a professor in the Salk Institute's Laboratory of Genetics and senior author of the paper, published October 8, 2015 in Cell Stem Cell.

"By using this powerful approach, we can begin to answer many questions about the physiology and molecular machinery of human nerve cells—not just around healthy aging but pathological aging as well," says Martin Hetzer, a Salk professor also involved in the work.

Historically, animal models—from fruit flies to mice—have been the go-to technique to study the biological consequences of aging, especially in tissues that can't be easily sampled from living humans, like the brain. Over the past few years, researchers have increasingly turned to stem cells to study various diseases in humans. For example, scientists can take patients' skin cells and turn them into induced pluripotent stem cells, which have the ability to become any cell in the body. From there, researchers can prompt the stem cells to turn into brain cells for further study. But this process—even when taking skin cells from an older human—doesn't guarantee stem cells with 'older' properties.

"As researchers started using these cells more, it became clear that during the process of reprogramming to create stem cells the cell was also rejuvenated in other ways," says Jerome Mertens, a postdoctoral research fellow and first author of the new paper.

Epigenetic signatures in older cells—patterns of chemical marks on DNA that dictate what genes are expressed when—were reset to match younger signatures in the process. This made studying the aging of the human brain difficult, since researchers couldn't create 'old' brain cells with the approach.Gage, Hetzer, Mertens and colleagues decided to try another approach, turning to an even newer technique that lets them directly convert skin cells to neurons, creating what's called an induced neuron. "A few years ago, researchers showed that it's possible to do this, completely bypassing the stem cell precursor state," says Mertens.The scientists collected skin cells from 19 people, aged from birth to 89, and prompted them to turn into brain cells using both the induced pluripotent stem cell technique and the direct conversion approach. Then, they compared the patterns of gene expression in the resulting neurons with cells taken from autopsied brains.

When the induced pluripotent stem cell method was used, as expected, the patterns in the neurons were indistinguishable between young and old derived samples. But brain cells that had been created using the direct conversion technique had different patterns of gene expression depending on whether they were created from young donors or older adults.

"The neurons we derived showed differences depending on donor age," says Mertens. "And they actually show changes in gene expression that have been previously implicated in brain aging." For instance, levels of a nuclear pore protein called RanBP17—whose decline is linked to nuclear transport defects that play a role in neurodegenerative diseases—were lower in the neurons derived from older patients.

Now that the direct conversion of skin cells to neurons has been shown to retain these signatures of age, Gage expects the technique to become a valuable tool for studying aging. And, while the current work only tested its effectiveness in creating brain cells, he suspects a similar method will let researchers create aged heart and liver cells as well.

http://www.news-medical.net/news/20151009/Scientists-can-now-use-skin-samples-from-older-patients-to-grow-brain-cells.aspx

Support for enteric nervous system pathology in prodromal PD

 October 22, 2015

By Lucy Piper, Senior medwireNews Reporter

Researchers have found positive immunostaining of α-synuclein in the enteric nervous system (ENS) of patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), suggesting it may have a possible role as a biomarker for prodromal Parkinson’s disease (PD).

iRBD is one of the conditions most representative of the PD prodrome, occurring in up to 80% of patients who go on to develop the disease, Werner Poewe (Medical University of Innsbruck, Austria) and co-researchers explain.

They report that four of 17 patients with this condition stained positive with a serine 129-phosphorylated α-synuclein (pSyn) antibody in the nerve fibres or ganglia of the colonic submucosa, along with one of 19 patients with PD. By contrast, immunostaining was negative for all of the 14 healthy individuals included in the study.

“Therefore, the present findings raise the possibility that ENS pSyn immunohistochemistry could help to identify those participants with iRBD who will go on to develop clinical PD and in whom RBD could be considered a prodromal manifestation of the disease”, the researchers comment in Neurology.

They add that their findings are “broadly consistent” with the theory that the ENS may be a site of initiation for α-synuclein pathology, a major component of Lewy bodies, that subsequently spreads via the vagal nerve to the brain.They point out, however, that the fact that only a single PD patient was positive for the marker does not fit with their suggestions and is “difficult to understand”. They speculate that once α-synuclein pathology is initiated in the ENS, rostral transmission or transport may be associated with the clearance of aggregated α-synuclein.

Studies on α-synuclein in the ENS to date have been inconsistent and Poewe and team suggest that this may be due to methodological factors.

Indeed, they found that positive immunostaining was specific to the pSyn antibody. The 15G7 α-synuclein antibody, which non-specifically binds to native α-synuclein, did not discriminate between patients and controls.

Also, depth of biopsies was critical, with pSyn immunopositivity seen in submucosal but not mucosal tissue.

In a related editorial, Marcus Unger (Saarland University, Saarbrücken, Germany) and Ryuji Sakakibara (Toho University, Sakura, Japan) say that the findings are “of notable importance”.

Despite colonic biopsies not being readily available as a diagnostic biomarker for prodromal PD, the results endorse the link between iRBD and PD and support the notion of a common pathology, they write.

“The results are compatible with current concepts of an early pathology in the ENS in PD (and iRBD) and imply that PD-related pathology might be detectable in vivo at a prodromal stage”, the editorialists conclude.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

http://www.news-medical.net/news/20151022/Support-for-enteric-nervous-system-pathology-in-prodromal-PD.aspx

Breakthrough advancements on new molecular mechanism may lead to Parkinson's treatments

Published on October 19, 2015

Posted Oct.26,2015

More than one million people in the United States are afflicted with Parkinson's disease, a progressive disorder of the brain that affects movement and coordination. The cause is typically unknown, and presently there is no cure for the disease.

Scientists have discovered that the hallmark sign of Parkinson's disease is the intraneuronal accumulation and progressive spreading of clumps in certain areas of the brain, known as Lewy bodies. These Lewy body inclusions are formed mainly through the accumulation of a protein, called alpha-synuclein. Because of a correlation between the extent of Lewy body clumps and the severity of the Parkinson's clinical symptoms, it has been largely accepted that these inclusions accelerate the disease process. Therefore, identifying molecules and conditions which decrease or halt the formation of alpha-synuclein-containing toxic inclusions may be beneficial for Parkinson's disease patients.

A research team led by Assia Shisheva, Ph.D., professor of physiology in Wayne State University's School of Medicine, has made breakthrough advancements on a new molecular mechanism that may provide a means to "melt" these pathological clumps.

For nearly 15 years, Shisheva's laboratory has studied the cellular functions of two enzymes, PIKfyve and Sac3, and one accessory protein ArPIKfyve - the three proteins originally discovered by her group from 1999 to 2007 - and the role these proteins play in disease mechanisms. Previous work by Shisheva's team revealed that if the Sac3 enzyme is not bound and protected by ArPIKfyve, it is prone to a quick demise inside the cell. In addition, they found that this double ArPIKfyve-Sac3 protein complex is a part of a bigger, triple assembly incorporating the PIKfyve enzyme as well. The triple complex controls the production and turnover of one rare phospholipid molecule that controls the traffic of membranes towards the digestive system of the cell.

It has remained a mystery why the Sac3 mutations are associated with neurodegeneration in humans, whereas the human mutations in PIKfyve are currently linked only to a relatively benign disease of the cornea. This led Shisheva's team to believe that the double ArPIKfyve-Sac3 complex has separate functions in the brain. Shisheva's group sought to identify brain-specific proteins that physically interact only with the double complex ArPIKfyve-Sac3.

neurodegeneration-related phosphoinositide phosphatase Sac3 and ArPIKfyve binds the Lewy-body-associated Synphilin-1 preventing its aggregation," published online in the Journal of Biological Chemistry, Shisheva and her research team characterized a novel interaction partner of the ArPIKfyve-Sac3 complex in the brain. The Journal of Biological Chemistry is the world's largest and most cited journal based on PageRank algorithm.

"We uncovered that the ArPIKfyve-Sac3 complex binds Synphilin-1, a protein already implicated in the pathogenesis of Parkinson's disease through its interaction with alpha-synuclein," said Shisheva. "As alpha-synuclein, Synphilin-1 is also entrapped in the abnormal Lewy body deposits. Our study revealed that the ArPIKfyve-Sac3 complex is an effective inhibitor of aggregate formation by Synphilin-1."

In addition, Shisheva's team found that excessive levels of Sac3 cause protein self-aggregation and further facilitate the clumping by Synphilin-1. Not surprisingly, researchers in Japan have recently found that excessive Sac3 accumulates in Lewy bodies. Therefore, the ArPIKfyve-Sac3 complex may precipitate Parkinson's disease manifestation in two ways: when it is too low and when Sac3 is disproportionally high. These observations raise the possibility that increasing the levels of the ArPIKfyve-Sac3 complex may have a beneficial effect in Parkinson's disease.

According to Shisheva, the ArPIKfyve-Sac3 complex could shift Synphilin-1 distribution from a form of multiple aggregates towards the soluble form. Future attempts to block aggregate formation or to break down formed aggregates of Synphilin-1 and, possibly, of alpha-synuclein, based on the ArPIKfyve-Sac3 complex may prove beneficial as a therapeutic approach in reducing neurodegeneration in Parkinson's disease. The current study provides new insights into the neurodegeneration mechanisms and important clues about novel molecular means for reducing cytoplasmic aggregates in Parkinson's diseases.

http://www.news-medical.net/news/20151019/Breakthrough-advancements-on-new-molecular-mechanism-may-lead-to-Parkinsons-treatments.aspx

Cognitive decline common and rapid in Parkinson’s patients

October 9, 2015 

Posted Oct.26,2015

Researchers report that nearly half of patients with Parkinson’s disease (PD) develop cognitive impairment within about a decade, and progress rapidly to dementia.

The 141 patients in the study had normal cognition at baseline and an average disease duration of 5.0 years. After 6 years of follow-up, the estimated cumulative rate of any cognitive impairment was 47.4%, with a mild cognitive impairment (MCI) rate of 43.0%.

And all patients diagnosed with MCI during the course of the study progressed to dementia within the next 5 years.

“These findings are in contrast to those reported for MCI in the general population, in which the majority of patients will not progress to dementia even after 10 years of follow-up”, say Daniel Weintraub (Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA) and study co-authors.

Naming Test, and the Hopkins Verbal Learning Test–Revised total recall and recognition discrimination were the best predictors of later cognitive impairment.

However, editorialists Linda Hershey (University of Oklahoma Health Sciences Center, Oklahoma City, USA) and Guerry Peavy (University of California, San Diego, USA) note that baseline global cognitive performance on the Dementia Rating Scale–2 also predicted cognitive decline.

“This may be particularly helpful in settings in which comprehensive cognitive evaluations and lengthy problem-solving discussions are not possible”, they say.

Hershey and Peavy highlight the importance of early recognition of cognitive decline, when it is potentially amenable to pharmacological intervention.

“In addition, strong evidence of early cognitive decline in PD underscores the importance of acknowledging and accurately labeling deficits in order to guide patients and caregivers with respect to their expectations and their ability to develop strategies to improve daily functioning.”

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

http://www.news-medical.net/news/20151009/Cognitive-decline-common-and-rapid-in-Parkinsone28099s-patients.aspx

Parkinson's Disease: Symptoms and Treatment (Physical Therapy)

Friday’s roundup: Cespedes gets cortisone shot

October 23, 2015

New York — Mets outfielder Yoenis Cespedes received a cortisone injection in his sore left shoulder, and the team expects him to be ready for the World Series next week.

Cespedes left Wednesday night’s National League Championship Series finale at Chicago in the second inning. The slugger had the injection Thursday and was told not to participate in baseball activities for 24 hours, Mets spokesman Jay Horwitz said. Cespedes did not attend Friday’s workout at Citi Field.

“We’ve got it taken care of,” Mets manager Terry Collins said. “The doctors, they said, look, he’ll be OK, and so tomorrow we’ll find out.”

Collins said he didn’t ask how Cespedes got hurt. Hitting coach Kevin Long said Cespedes thought he did it doing push-ups.

“He didn’t do it playing golf. He didn’t have a bad sand shot or didn’t get stuck in the side of a bunker,” Collins said.

Cespedes was traded to the Mets from the Tigers at the trade deadline in July.

Mariners hire manager

The Mariners hired former big league catcher Scott Servais as their manager, giving the job to someone with ties to the new front office but no experience running a team.

Servais, 48, replaces Lloyd McClendon, a former Tigers coach who was fired this month after Seattle went 76-86.

Servais will be formally introduced by the team next week.

He has worked the past five seasons as an assistant general manager for the Angels and worked alongside

Jerry Dipoto for most of that time. Dipoto resigned as Angels general manager July 1.

Around the horn

Ten weeks after being diagnosed with cancer, Red Sox manager John Farrell was given a clean bill of health by his doctors and was cleared to resume regular activities to the extent his body will allow.

“The news … is a huge relief to me,” Farrell said during a conference call with reporters one day after Red Sox officials announced his cancer was in remission. “It beat me up a little bit physically, but right now I’m feeling pretty darn good.”

Farrell, 53, was diagnosed with non-Hodgkin’s lymphoma on Aug. 14 and immediately took a leave of absence from the team. Bench coach Torey Lovullo took over in his absence, managing the team to a 28-20 record the rest of the way.

President of baseball operations Dave Dombrowski announced on the final day of the season Farrell would be back next year. Lovullo was convinced to forgo a chance to manage elsewhere to remain as bench coach.

“It says a lot about Torey’s commitment here,” Farrell said.

... The Phillies finished the season in the cellar. But that didn’t keep the Phanatic from engaging in some rooftop shenanigans.

The beloved team mascot rappelled 31 stories down the face of a skyscraper. That’s a 418-foot drop.

The event was a fundraiser for the Outward Bound School, which offers outdoor programs aimed at building character and leadership skills.

Organizers say the goal was for 100 people to rappel during the all-day event.

Four rope lines dangled from the One Logan Square office building as a small crowd cheered in a courtyard.

... The Marlins have considerable interest in hiring former Yankees star Don Mattingly as their next manager, and Mattingly has interest in the Marlins after parting ways with the Dodgers this week, multiple sources told The Miami Herald.

Mattingly, 54, has emerged as the front-runner and the Marlins are expected to initiate discussions in the next few days. It's premature to say Mattingly-to-the-Marlins definitely will happen, because the sides haven't had a meeting yet and it's unclear if Mattingly will have other options.

http://health.einnews.com/article/293236819/hKvH7HsC0pAia4Jk