Alzheimer's beginnings prove to be a sticky situation

September 12, 2016 by Layne Cameron , Lisa Lapidus

MSU's Lisa Lapidus uses lasers to reveal a common trait of Alzheimer's beginnings. Credit: G.L. Kohuth

Laser technology has revealed a common trait of Alzheimer's disease - a sticky situation that could lead to new targets for medicinal treatments.

Alzheimer's statistics are always staggering. The neurodegenerative disease affects an estimated 5 million Americans, one in three seniors dies with Alzheimer's or a form of dementia, it claims more lives than breast and prostate cancers combined, and its incidence is rising.

To help fight this deadly disease, Lisa Lapidus, Michigan State University professor of physics and astronomy, has found that peptides, or strings of amino acids, related to Alzheimer's wiggle at dangerous speeds prior to clumping or forming the plaques commonly associated with Alzheimer's.

"Strings of 40 amino acids are the ones most-commonly found in healthy individuals, but strings of 42 are much more likely to clump," said Lapidus, who published the results in the current issue of ChemPhysChem. "We found that the peptides' wiggle speeds, the step before aggregation, was five times slower for the longer strings, which leaves plenty of time to stick together rather than wiggle out of the way."

This so-called "wiggle" precedes clumping, or aggregating, which is the first step of neurological disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Lapidus pioneered the use of lasers to study the speed of protein reconfiguration before aggregation.

If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow. If reconfiguration is the same speed, however, aggregation is fast. She calls the telltale wiggle that she discovered the "dangerous middle."

"The dangerous middle is the speed in which clumping happens fastest," Lapidus said. "But we were able to identify some ways that we can bump that speed into a safer zone."

Lapidus and her team of MSU scientists, including Srabasti Acharya, Kinshuk Srivastava and Sureshbabu Nagarajan, found that increasing pH levels kept the amino acids wiggling at fast, safe speeds. Also, a naturally occurring molecule, curcumin (from the spice turmeric), kept the peptide out of the dangerous middle.

While this is not a viable drug candidate because it does not easily cross the blood-brain barrier, the filter that controls what chemicals reach the brain, they do provide strong leads that could lead to medicinal breakthroughs.

Along with new drug targets, Lapidus' research provides a potential model of early detection. By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains. Policing amino acids for wiggling at dangerous speeds could tip off doctors long before the patient begins to suffer from the disease.

Journal reference: ChemPhysChem

Provided by: Michigan State University

http://medicalxpress.com/news/2016-09-alzheimer-sticky-situation.html

Dolly Parton rallies behind fellow singer’s Parkinson’s battle

September 12, 2016

You might remember the trio of magical voices that was Dolly Parton, Emmylou Harris and Linda Ronstadt.

Now the trio have reunited but the tragic reason behind is absolutely heartbreaking.

Dolly and EmmyLou are rallying behind Linda Ronstadt as she battles Parkinson’s Disease.

Speaking on the Sunday Night program last night, Dolly revealed she is one of Linda’s biggest fans.

“Linda is such a voice she can sing anything I personally think Linda’s one of the greatest singers ever including Streisand or anybody,” she said.

“I mean Linda probably has the most stunningly beautiful voice of our generation.

“When I first heard her when I was knocking around the clubs in New York, I didn’t meet her then. But I saw her, and I was incredibly jealous.”

She also spoke about how proud she was about being part of the famed Trio.

“I have to honestly say that there are some things in your life that you pick out and think that is one of the greatest things that I was ever a part of,” she said.

“Linda Ronstadt, who’s unbelievably great, and Emmylou who’s spectacular and I’m just I just feel so proud to be part of that trio.”

Linda’s health has been in decline for several years and unfortunately, she’ll never be able to sing again.

She opened up to the program about how Parkinson’s is taking it’s toll on her life.

“There’s a lot of things I can’t do, I can still read, but it’s, sometimes hard to keep the book steady, that’s what I mostly do, I read and talk to people. I can’t walk very well, you know,” she said.

“From the minute I get up I have a hard time brushing my teeth, washing my hair, standing in the shower… I have a hard time standing or sitting, I can’t sit up straight in a chair like I can’t sit up at the table and eat.”

You might remember Linda’s big hit Blue Bayou in the ’70s?

Well, it turns out she’s critical of her biggest track.

“I never like to hear myself,” she said.

“Blue bayou is a hard song to sing as it’s too low and too high, at the same time you’ve got to pick out whether you’ve got to be too low or too high always picked out too low.”

The Trio of EmmyLou, Dolly and Linda came together in 1974 and recorded their first album in 1987 and another in 1999 – winning three Grammy’s and selling millions of albums along the way.
Like family, Dolly and EmmyLou have been supporting Linda since her health declined after their second album together.

“I knew something organic was wrong with my voice, I knew it wasn’t nerves, or, and I kept going to the doctor and he’d go, oh, I don’t see anything wrong with your vocal cords, must be in your mind, and I’m going, no, it’s not in my mind, I knew something was really major wrong,” Linda said.

“I listen to other people sing now… I can still sing in my mind.”

As their final project together, the Trio have released a digitally remastered album with some unreleased material from their original sessions.

To see other video:

https://startsat60.com/stories/news/dolly-parton-rallies-behind-fellow-singers-parkinsons-battle

The Basic Psychiatric Symptoms Associated with Parkinson Disease

by admin | Sep 12, 2016 

It is understandable that a patient goes through a lot of mental disturbance the moment he is diagnosed with any sort of illness. The Parkinson’s disease is one of the most dangerous brain diseases, widely spreading and affecting more than 2 million of the total population of America.

However, there is no definite cure for the disease found yet, but there is hope with the use of medication and certain precautions. There are a few defined psychiatric symptoms in the patient of this disease, which can be easily identified during the initial stages of the disease.

Anxiety and Depression:

When the probable patient of the Parkinson disease is facing the diagnosis procedure of the Parkinson’s disease, the patient would be anxious, like all other patients of other illnesses. It is logical if one feels insecure with their health, but a mood disorder is the basic symptom which is not found in all of the other diseases. The disorders of anxiety and depression are clinical in the regard of this disease, which would likely promote and provoke rigidity, shiver, and shock. These symptoms of depression are found in about 40 percent of the Parkinson’s patient.

Clinical depression is highly dangerous for the patient, and it can have long-term effects on the patient. The symptoms of anxiety and depression also include social anxiety problems, which can further lead to the mismanagement of exercising for potential motor symptoms and a lethargic manner of dealing with medication and care. Therefore, these symptoms of depression can be treated with the use of proper medication, or counseling, etc. The patient requires encouragement, motivation and constant support in order to recover efficiently.

Cognitive Impairment:

Another troublesome form of psychiatric illness closely linked to the Parkinson’s disease, which is the cognitive impairment. This illness mostly tends to affect the people with the Parkinson’s disease, which spontaneously lead to the motor symptoms, which can result in the slow processing of memory and also effects the patient’s thinking skills. Other than that, stress, and depression can also contribute to these subtle changes, and thus, it is important to identify what is the actual cause of these symptoms.

It should be acknowledged that cognitive impairment can be completely opposite from dementia, which is a much more severe loss to the intellectual abilities of the patient. However, cognition is quite difficult and vast to define, mostly for the reason that it covers various mental capabilities and activities. Overall it refers to the working process of the brain, specifically the sense of perception of the world around us, the ability to store and retrieve memories, problem solving, triumphing insights, concept formation, and other activities linked to the working of the brain.

Coming to the conclusion, the medication associated with the depression, linked to the Parkinson disease, depends upon the overall condition of the patient, and his specific needs. This is essential because there are certain medicines which can worsen the disease symptoms of the probable patient.

http://www.alifewithparkinsons.com

The 4th World Parkinson Congress Announces Its 12 Hot Topics In Research

September 12, 2016 - PORTLAND, OREGON

Promising, Rising-Star Researchers and Clinicians Present New Study Findings in Parkinson’s Disease

4th World Parkinson Congress Steering Committee Co-Chairs Serge Przedborski, MD, PhD and A. Jon Stoessl, CM, MD, FRCPC

The 4th World Parkinson Congress (WPC 2016), through the organization the World Parkinson Coalition®, announces today its 12 Hot Topics presentations, which highlight emerging areas of study in Parkinson’s research and patient disease management. The hot topic categories include basic science, clinical science, clinical therapeutics, and complementary care. The World Parkinson Coalition leadership, which includes more than 50 reviewers, assessed over 600 submissions and whittled them down to the final 12 abstracts. 

Authors of the selected abstracts are presenting their findings orally to the broader audience, just before the opening plenary each morning, four per day. WPC 2016 is being held in Portland, Ore., September 20 – 23. 

“We are pleased to announce this year’s most exciting, cutting-edge 12 hot topics in science by up and coming researchers and clinicians whose work adds great value to the Parkinson’s community,” states Elizabeth (Eli) Pollard, executive director, World Parkinson Coalition, the nonprofit, international organization behind the Congress. “The vast array of research, from genetics to improving day-to-day living, is further evidence how the global Parkinson’s community is working toward the common goal of improving disease management and in finding a cure.” 

The aim of the WPC 2016 is to unite the worldwide Parkinson community for a high-level scientific and educational program organized into four days of pre-congress courses, plenary sessions, workshops, and discussions on the most recent science and clinical research as well as advances in treatments designed to improve care and quality of life for people living with Parkinson’s disease. 

The WPC 2016 committee chairs and co-chairs, such as Serge Przedborski, MD, PhD; A. Jon Stoessl, CM, MD, FRCPC; Marie-Francoise Chesselet, MD, PhD; Peter LeWitt, MD and Peter Fletcher, MSc, FRCP, are among the highly prominent experts in Parkinson’s who reviewed the submitted abstracts that were chosen for the 12 Hot Topics presentations.

WPC 2016 12 Hot Topics presentations include: 

•     Early detection: How sleep disorders may be associated with Parkinson’s years before telltale signs of the disease appear and how early intervention may help stave off disease onset;
•     Genetics: The genetic connections between cognitive impairment and Parkinson’s and the implications for best practices in disease management; how inhibiting the enzyme that causes breakdown of certain neurotransmitters in the brain may slow down the causes of Parkinson’s disease in some people; further understanding of the underpinnings of how Parkinson’s develops to ultimately find a targeted approach for treating Parkinson’s; and other factors that affect dopamine neurons;
•     Traumatic brain injury and Parkinson’s – finding a connection;
•     How to talk to children about Parkinson’s through story books;
•     The possibility of engineering neurological pathways to improve/repair pathways for dopaminergic neurons;
•     Evidence that the flu vaccine may help ward off Parkinson’s;
•     The effects of exercise on people with Parkinson’s; 
•     Technology: How wearable technology and apps improve lives for people living with Parkinson’s.    

For more information about the abstracts, please visit the WPC 2016 Hot Topics page: http://www.wpc2016.org/HotTopics.

About the World Parkinson Coalition® and WPC 2016 

The World Parkinson Coalition Inc. is a nonprofit organization that provides an international forum for learning about the latest scientific discoveries, medical practices, care partner initiatives and advocacy work related to Parkinson's disease. The World Parkinson Coalition® launched the first Congress in 2006 to provide a space for the global Parkinson’s community of researchers, clinicians, health care professionals, people with Parkinson’s and their care partners to meet in person, network and to share advances in Parkinson’s research, improve understanding and promote advocacy worldwide, and to potentially shape future research, treatment and care. 

From its modest beginning to nearly 10,000 delegates who have participated in the previous triennial Congresses, the WPC 2016 is expected to attract more than 4,000 delegates. To learn more about the 4th World Parkinson Congress, please visit: http://www.wpc2016.org/

http://www.prweb.com/releases/2016/09/prweb13662807.htm

Brain pacemakers without side effects

September 12, 2016

For Parkinson's disease (PD) patients whose symptoms cannot be controlled by medication, 'Deep brain stimulation' (DBS) may be the only hope. While DBS is generally considered to be safe, side effects related to the stimulation may occur in some cases, including numbness or tingling sensations, muscle tightness, speech or balance problems and unwanted mood changes. The IMPACT project has set out to counter these side-effects by bringing DBS to the next level.

The IMPACT (Improving the lives of Parkinson's disease patients while reducing side effects through tailored deep brain stimulation) team initiated its work with one premise: the main problem with current DBS practice lies in the fact that physicians do not have the tools needed to provide personalised treatment. Stimulation outside the intended target region occurs in 15 to 30 % of DBS patients and leads to side effects and less effective therapy delivery.

The EUR 5 million IMPACT project has spent the past four years trying to develop a 'direct-feedback, image-based expert tuning tool to improve the positioning and programming (tuning) of "Steering brain stimulation" (SBS) implants in a patient-specific manner'. In other words, instead of targeting a larger average area, the new software will help the clinician to place the stimulation field exactly where it should be, taking into account the specifics of each patient's brain anatomy.

One month ahead of the project's end, Hubert Martens, Director of Product Development at Medtronic and coordinator of the project, discusses the physician tool developed by his team. This new tool combines pre- and post-operative imaging data (MRI, X-ray), high-resolution electrical recordings of the patient's brain activity and bio-statistical data about DBS target areas. Prototypes are already under clinical evaluation.

What are the main shortcomings of current DBS systems?

DBS is a great therapy, but less precise delivery of stimulation may elicit unwanted side effects. Improved precision is required. In essence, the optimisation of the therapy after surgery is a trial-and-error process. There are currently no tools that guide the clinician to the most optimal position in a time-efficient manner.

How does the technology you developed contribute to solving these problems?

In IMPACT, we have focused on the usage of imaging, advanced modelling and analysis to precisely identify areas of the brain which need to be stimulated for an optimal effect, as well as areas to be avoided because they are closely related to certain side effects. We integrated that information into algorithms and an intuitive tool which is able to help guide programming decisions by a physician managing the therapy for DBS patients.

http://medicalxpress.com/news/2016-09-brain-pacemakers-side-effects.html

Infant Epilepsy Caused by Clumping of Parkinson’s Protein, According to Australian Study

SEPTEMBER 12, 2016 Magdalena Kegel

Researchers have found that a protein known to cause epilepsy in infants does so by a trigger clumping the alpha-synuclein protein — a process causing brain toxicity that is more commonly linked to Parkinson’s disease.

The study, “Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation,” published in the Journal of Cell Biology, advances the understanding of this serious conditions in newborns, and may lead to the development of new types of treatments for the disease.

Munc18-1 is a protein belonging to the array of molecules that control the release of neurotransmitters — the molecules acting as chemical messengers, allowing a signal to pass from one nerve to the next.

Mutations in the gene coding for Munc18-1 lead to developmental problems and the rare type of epilepsy known as infantile epileptic encephalopathy (EIEE). Only about half of babies that are diagnosed with the condition survive.

“We already knew that mutations in the molecule known as Munc18-1 triggered this rare epileptic syndrome, but this groundbreaking study, led by PhD student Ye Jin Chai, has isolated the exact process,” senior author Fred Meunier, a professor from the Clem Jones Centre for Ageing Dementia Research at Australia’s University of Queensland, said in a news release.

The research team discovered that when Munc18-1 was mutated, the protein alpha-synuclein — normally present throughout the brain — started aggregating into clumps, much like researchers observe in the brains of patients with Parkinson’s disease and related conditions. These clumps are toxic to neurons, causing the degeneration seen in these conditions.

This is not the first time that alpha-synuclein, a protein mainly studied in the context of neurodegeneration, is linked to epilepsy. A study of patients with epilepsy not responding to treatment found elevated levels of the protein in the cerebrospinal fluid, and another study found that the protein expression in brains of patients with mesial temporal lobe epilepsy differ from that of healthy people.

However, researchers have never before observed the aggregation of the protein — a process so far mainly linked to neurodegeneration — in an epileptic state.

“This is the first time that a communal mode of action has been found for an epileptic syndrome and neurodegeneration,” said Dr. Emma Sierecki from the University of New South Wales, a co-author on the study who is focusing her research on protein aggregation linked to neurodegenerative diseases.

http://epilepsynewstoday.com/2016/09/12/infant-epilepsy-caused-by-clumping-parkinsons-protein

Markers associated with Alzheimer’s and Parkinson’s diseases are present in Mexico City children chronically exposed to concentrations of fine particulate matter PM2.5 above the current EPA USA standards

September 12, 2016

A new study by researchers at the Universities of Montana, Valle de México, Boise State, Veracruz University, Médica Sur, Centro de Ciencias de la Atmósfera, UNAM, Hospital Regional de Alta Especialidad, Ciudad Victoria, Hospital de Especialidades #14, IMSS, Centre Hospitalier Universitaire, Hôpital de Hautepierre and AJ Roboscreen GmbH heightens concerns over the detrimental impact of fine particulate matter PM2.5 on CSF markers associated with Alzheimer and Parkinson’s diseases in children ages 11.9±4.8 years. These findings are published in the Journal of Alzheimer’s Disease. 

Mexico City (MC) children have lifetime exposures to concentrations of air pollutants above the current USA standards, including fine particulate matter (PM 2.5). Metropolitan Mexico City is an example of extreme urban growth and serious environmental pollution including high exposures to PM 2.5, ozone, polycyclic aromatic hydrocarbons (PAH), metals, endotoxins, tobacco smog, open waste dumps, highly polluting heavy duty trucks (not subjected to any pollution controls), etc., resulting in millions of children involuntarily exposed to harmful air neurotoxic substances every day since conception.

The results of this study including the significantly low concentrations of Aβ 1-42 and Brain-derived neurotrophic factor (BDNF) in MC children versus controls, suggests that major changes in key neural proteins playing major roles in neurotoxicity, cell survival, axonal and dendritic growth, and synaptic plasticity are evolving in urban MC children. Decreased levels of BDNF are associated with the development of obesity, depression, mood disorders, and neurodegeneration. Interestingly, Mexico City children increased their levels of total prion protein (TPrP) with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age. The low values of this key protein are likely detrimental given its protective effects against oxidative stress and its role in cell signaling, metal interactions, memory, myelin maintenance, axonal growth and neuronal development. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years, while the abnormal synuclein associated with Parkinson’s disease exhibited a tendency to increase with cumulated PM2.5.

Mexico City children, teens, and young adults have shown a key marker of Alzheimer disease (AD): hyperphosphorylated tau along significant brain and intrathecal neuroinflammation, dysregulated immune responses, breakdown of epithelial and endothelial barriers, damage to the neurovascular unit, and brain accumulation of metals associated with combustion. Moreover, seemingly healthy children in Mexico City have olfaction deficits, dysregulation of feeding regulatory hormones, deficiencies in attention and short-term memory, and below-average scores in Verbal and Full Scale IQ compared to low air pollution children.

“Researchers are very concerned young Mexico City urbanites exhibit evidence of spectral markers of neurodegeneration that are often seen in adults with mild cognitive impairment, in Alzheimer patients and in mouse models of Alzheimer’s disease” said Dr. Lilian Calderón-Garcidueňas.

“Our concern about Parkinson’s disease is also increased when we observed children and teens with early autonomic dysfunction and in brainstem materials, extensive accumulation of α- synuclein in key nuclei including auditory nuclei and the dorsal nucleus of the vagus” said authors.

“These results add to growing data from our laboratory and others, suggesting urban residents with chronic high exposures to ozone and fine particulate matter have a higher risk for developing Alzheimer’s disease (Jung et al., J Alzheimers Dis, 44, 573-584, 2015) and the potential key role of environmental magnetite nanoparticles in the brains of Mexico City residents (Maher et al., Proc Natl Acad Sci U S A, early edition) commented Dr. Calderón-Garcidueňas.

Air pollution is a serious public health issue and exposures to concentrations of air pollutants at or above the current standards have been clearly linked to neuroinflammation and neurodegeneration.

There is an urgent need for studying air pollution interactions impacting children’s brains and their responses, which could provide new avenues for Alzheimer’s and Parkinson’s disease prevention.

The authors concluded: “We have a 50-year window of opportunity between the time urban children experience the detrimental effects we are describing here and when they will present with mild cognitive impairment, dementia, tremor or all of the above. Our efforts should be aimed to identify and mitigate environmental factors influencing the early development of neurodegenerative diseases and to neuroprotect high risk children. Unfortunately, to date there has been no support for studying the detrimental neurodegenerative effects of air pollution on the pediatric brain.”

# # #

Contact:

Lilian Calderón-Garcidueňas, MA, MD, PhD

Biomedical Sciences

University of Montana

+1 406 243 4785

lilian.calderon-garciduenas@umontana.edu

http://www.healthcanal.com/brain-nerves/brain-diseases/alzheimer’s/74648-markers-associated-with-alzheimer’s-and-parkinson’s-diseases-are-present-in-mexico-city-children-chronically-exposed-to-concentrations-of-fine-particulate-matter-pm2.5-above-the-current-epa-usa-standards.html

Cancer drug may offer hope for Parkinson's and dementia patients

September 11, 2016

ROCHESTER – A local doctor is helping to treat a patient with Lewy body dementia, using an off-use drug recently tested on dementia patients, and he and the husband of the patient say there is no reason why the ongoing controversy between research organizations and the lack of support from insurance companies should stand in the way of the drug helping patients now, instead of years from now.

A small pre-clinical trial done in 2015 at Georgetown University showed remarkable results in using the FDA-approved leukemia drug nilotinib to treat patients with late stage Parkinson’s disease and dementia. The results of the trial showed marked improvement in both the cognitive and mobility capabilities of the patients.

In a press release from Georgetown University, researchers indicated that further and more controlled clinical trials needed to be completed before they would recommend nilotinib as being safe to treat dementia and Parkinson’s patients.

After much research, Dr. Terry Bennett agreed to prescribe nilotinib to treat Salem resident Madeline Carano, at the request of her husband of 65 years, Don Carano. Both say the results of the study are too compelling to wait because by the time the trials are completed years will be lost to patients who need help now.\

Carano is so devoted to his wife and her care that he is paying out-of-pocket, a significant amount of money monthly to treat his wife, under Bennett’s supervision. He has signed a hold-harmless document with Bennett.

“Why are we not doing an accelerated program to get this job done?” asked Bennett. “The results of this FDA-approved drug are incredible. Dementia patients are making too much of a tau protein and this drug basically dissolves them. It is so effective, that people’s conditions are reversing back to an earlier stage where they functioned well while they take nilotinib. Take them off it and they regress.”

In fact, Bennett is so excited by the treatment that he is hoping more patients seek him out so he can prove the treatment is effective. He said the effects take about four months to see improvements.

Madeline Carano has been taking the drug for about one month. Don Carano said he not only had to find a doctor who would prescribe nilotinib, he had to find a pharmacy that would fill the prescription as an off-use drug. The retired businessman so believes he will help his wife he has framed the prescription from Bennett.

“I was in financial services for 42 years and I have the resources to afford this, and I am paying market price,” Carano said. “I think it is shameful that this is not being made available and that insurance companies are not willing to cover it.”

Bennett agrees.

“Why are they holding hostage a drug that could help millions of people?” said Bennett. “I think it's a battle over money, who will ultimately end up holding the patent for this. Georgetown, the Michael J. Fox Foundation and the insurance companies are controlling this.”

Carano said he searched the United States, Canada and England, looking for a doctor to work with before finding Bennett.

“All I heard was negatives,” Carano said. “Well, I did more research and asked doctors treating leukemia with the drug how many of their patients had dementia. The answer is none. I challenge doctors to look at that themselves.”

Carano has spoken to two of the people involved in the Georgetown University trial.

“One woman, 89, did not communicate and had been in bed for three years,” said Carano. “Within six months, she was out of bed, talking in sentences and knew her relatives again. A man, a former professor is out of his wheelchair. He reads, grills and even drives to the grocery store. Why would I not want this for my wife? I have been told there is a risk of sudden death, 5-6 percent. We are talking about elderly patients. People die. Why not try it? I do not believe this poses a significant risk or I would never have pursued it.”

Dr. Charbel Moussa, who directs Georgetown’s Laboratory of Dementia and Parkinson’s, conducted the preclinical research of nilotinib (Tasigna by Novartis), an FDA-approved drug for leukemia, assisted by Dr. Fernando Pagan, associate professor of neurology, who directs the movement disorders program at MedStar Georgetown University Hospital. In the press release, they reported that the drug improved cognition, motor skills and non-motor function in patients with Parkinson’s disease and Lewy body dementia and led to statistically significant and encouraging changes in toxic proteins linked to disease progression (biomarkers). The complete data was presented at Neuroscience 2015, the annual meeting of the Society for Neuroscience, in Chicago on Oct. 17, 2015.

“To my knowledge, this study represents the first time a therapy appears to reverse — to a greater or lesser degree depending on stage of disease — cognitive and motor decline in patients with these neurodegenerative disorders,” Pagan said. “But it is critical to conduct larger and more comprehensive studies before determining the drug’s true impact.”

Investigators reported that the six-month, dose-escalating study of nilotinib produced benefit for all study patients who completed the trial (11 of 12), with 10 patients reporting meaningful clinical improvements. Patients also showed positive changes in relevant cerebrospinal fluid biomarkers of Parkinson’s.

The researchers say the nilotinib trial was not compared to a control group, nor was it compared with a placebo or other medications used to treat Parkinson’s in the study. However, the researchers said that during nilotinib use by the participants, production of dopamine increased in many patients, requiring doses of L-dopa and other dopamine-sparing drugs used to treat Parkinson’s to be lowered or stopped. Stopping nilotinib treatment appears to lead to cognitive and motor decline despite reinstating L-dopa therapies. The study’s primary objective was to test safety. Researchers say that use of nilotinib, in doses much smaller than are used to treat cancer (which is up to 800 milligrams daily), was well tolerated with no serious side effects. In addition, researchers found that the drug penetrates the blood-brain barrier in amounts greater than dopamine drugs.

But the observed efficacy in cognition, motor skills and non-motor function improvement (such as constipation) for many patients was the most dramatic result, Pagan said. The investigators report that one individual who was using a wheelchair was able to walk again; three others who could not talk were able to hold conversations.

“Study participants with earlier stage disease responded best, as did those diagnosed with Lewy body dementia, often described as a combination of Parkinson’s and Alzheimer’s diseases,” Pagan says.

According to the release, Alan Hoffman, Ph.D., a retired professor of social science education at Georgia State University, was diagnosed with Parkinson’s disease in 1997 and has participated in several clinical trials with no benefit, he says, until he enrolled in Pagan’s study.

“Before the nilotinib, I did almost nothing around the house. Now, I empty the garbage, unload the dishwasher, load the washer and the dryer, set the table, even take responsibility for grilling,” he says.

In the three weeks before enrolling in the study, Hoffman says he fell eight times, but only fell once during six months on the study. His speech has improved, as has his thinking.

“My wife says it’s life-changing for her and for my children and grandchildren,” Hoffman said. “To say that nilotinib has made a change in our lives is a huge understatement.”

Moussa and other Georgetown researchers are now planning larger clinical trials with nilotinib for patients with Parkinson’s and other similar diseases including Alzheimer’s disease.

Representatives from the Michael J. Fox Foundation for Parkinson’s Research approached GU about helping to fund the continued research. Disputes between the two groups have stalled trials and the MJF Foundation staff members say they will conduct their own trials.

According to Novartis, the cost of nilotinib for the treatment of CML is about $10,360 a month for 800 milligrams daily. The dose used in this study was 150 and 300 milligrams daily.

Pagan reported having no personal financial interests related to the study. The phase I study received philanthropic funding and was supported by the Georgetown-Howard Universities Center for Clinical and Translational Science.

“How can you be a doctor, know what this drug can do and never write another prescription?”’ said Carano. “My wife was never sick, until this, and raised six children. She was a beautiful woman and she will be again. I want to get her back. Muhammad Ali was a world treasure. I believe this could have been used and he would still be here. Every day we delay this treatment hurts so many more people.”

Carano and Bennett have agreed to allow the progress of his wife to be followed and they believe there will be positive outcomes to report, beginning in a few months.

http://www.seacoastonline.com/news/20160911/cancer-drug-may-offer-hope-for-parkinsons-and-dementia-patients

A record-breaking walk

Nicholas Johansen - Sep 10, 2016

About 250 people walked to support Parkinson's disease research Saturday morning, smashing the previous record for funds raised.

Saturday's walk raised $50,002 through sponsorships of those walking, beating the previous record of $44,700.

This was the seventh time the walk has been held in Kelowna, and the 39th year walks have been held across Canada.

Parkinson's disease is a degenerative disease that generally affects people over the age of 60. There is no cure for it.

Bob Thompson, director of Parkinson Society of British Columbia, says as the baby boomer generation gets older and a larger percentage of the population fits into the affected age category, more people will be diagnosed with the disease.

“By the time we get to 2020 or 2030, that's a lot of people that we've got to deal with,” Thompson said. “If there's a message, its learning to learn about Parkinson's and to understand that it takes money to provide the research to find a cure.”

The Parkinson Society British Columbia estimates 13,300 people in B.C. are living with the disease today.

The Parkinson SuperWalk was held in 20 communities across B.C. on Saturday.

http://www.castanet.net/news/Kelowna/175595/A-record-breaking-walk