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December 23, 2019

My first Day in the Hospital !

I AM SENDING MY APOLOGIES TO YOU!

I just returned after 14 days from the hospital, including Therapy.

A nurse will evaluate me tomorrow, Christmas eve, to see what kind of therapy is needed to
get me back to the best I can be.

Dec. 23, 2019

As soon as I can, I  will be back online. Have a very Merry Christmas!

God Bless!

Understanding What Parkinson’s Progression Means to Each Patient

DECEMBER 6, 2019 BY DR. C

Every day following the ruin of stagnation, it seems that I have progressed from early Parkinson’s to a moderate stage of the disease. But I can’t be sure. Many other factors, including stress, injuries, medication changes, and aging, could be making it look and feel worse. To appease my quandary, I dove into the internet, searching for elucidation about Parkinson’s progression.

We watched as Michael J. Fox and Muhammad Ali were changed by the disease. Granted, their Parkinson’s symptoms were dramatic: Their body movements gradually became less fluid, the tremors more pronounced. Over time, the movement challenges became more noticeable, signifying progression. The Parkinson’s community uses the terms “early,” “middle,” and “late” stage to describe progression. It mostly makes sense and matches what medical providers identify with patients. But it doesn’t help me in my search for well-being possibilities.

Progression for me is more than “early,” “middle,” or “late.” I accept that the disease will cause changes in me and my life. But it would be helpful for my wellness map if some of the pitfalls could be marked, “Danger ahead!” or, “Here’s a list of supplies,” to get me through the hardest parts of my chronic disease journey. Being well-prepared is an essential part of wellness success. The progression of Parkinson’s is not about stages — except in a general way. Rather, it means having some idea about what can be done to slow the progression, or, failing that, how to recognize when progression is happening. Useful information about progression would help guide us through what is sometimes a tortuous journey. It might make the trip easier.

Chatting with the Parkinson’s community reveals the entrenched idea that progression is unique to each person. It would be helpful if our understanding of progression could provide for each patient more details than, “It’s unique to everyone, and you will know when you get there.” So what’s holding up progress toward understanding disease progression?

Medical professionals determine Parkinson’s progression by a system involving a physical exam, patient report, and sometimes a standardized measurement tool or questionnaire. That system fails when all that we are told about progression is, “You’ll know it when you get there.” We need better information from early Parkinson’s stages to understand progression to middle and beyond. Data from the existing collection system is insufficient to give a clear understanding of what progression means to each patient.

I recently read an article in which the authors discuss the merits of the retropulsion test to evaluate postural instability in Parkinson’s. The three methods are: “(1) the pull test as described in the MDS-UPDRS scale; (2) using an unexpected shoulder pull, without prior warning; and (3) the push-and-release test.” Although the test is considered the gold standard, the authors state that “the outcome can vary considerably due to variability in test execution and interpretation.”

The authors state that the test fails to predict future falls, explaining that falling results from the “complex interplay between gait, balance, cognitive decline and environmental factors, and the retropulsion test captures only part of that.”

It is difficult to spot early symptoms during a short office visit once every three to six months. Increasing the speed of care by reducing the duration of clinic appointments has not improved healthcare for this ailing columnist. It hinders the ability of the healthcare practitioner to get to know the patient better and increases the chance of the latter being categorized as “that patient with Parkinson’s.” The provider can’t see all the effects of the chronic disease, even with a longer visit.

We have good and bad days, on and off periods, and life circumstances — all of which make data collection on Parkinson’s progression from a 15-minute office visit problematic. It makes sense that early diagnosis and proper treatment should make a difference in progression. As far as I can tell, no adequate longitudinal studies exist that describe variation in progression as a result of treatment, or lack thereof. This applies even to exercise, my favorite Parkinson’s treatment to slow progression, and the effects of stress as my “most need to avoid” situation to prevent speeding up the progression.

In the next column, I will offer a possible solution to the Parkinson’s progression research problem. 

***

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/2019/12/06/parkinsons-progression-part-1-stages-postural-instability-falls/

Dosing Begins in Phase 2 Trial of CNM-Au8, Potential Therapy for Dopaminergic Neurons

DECEMBER 6, 2019   BY PATRICIA INACIO, PHD

A pilot Phase 2 study evaluating CNM-Au8, an investigational Parkinson’s treatment aiming to protect nerve cells, has started dosing patients, the therapy’s developer, Clene Nanomedicine, announced.

The open-label REPAIR-PD (NCT03815916) clinical trial is enrolling up to 24 people, ages 30 to 80 and diagnosed within the past three years, at its one site at the University of Texas Southwestern Medical Center.

“We are excited to be advancing CNM-Au8 clinically into Parkinson’s patients starting with the REPAIR-PD Phase 2 study” Rob Etherington, president and CEO of Clene, said in a press release.

Parkinson’s disease is characterized by the death of dopaminergic neurons in two brain regions, the striatum and the substantia nigra. These nerve cells rely on large amounts of energy to function, which is provided by mitochondria, the cell’s powerhouses. Failure to provide the energy that cells need contributes to their death.

Oxidative stress, an imbalance between the production of harmful free radicals and the ability of cells to detoxify them, is another hallmark of Parkinson’s disease. These free radicals, or reactive oxygen species, are produced during certain metabolic reactions that involve mitochondria, and can damage cells.

CNM-Au8 is a suspension of nanocrystalline gold designed to increase the production of energy. Specifically, it works by increasing the speed of conversion between two molecules — nicotinamide adenine dinucleotide (NADH) to its oxidized form (NAD+) — resulting in greater production of energy in the form of ATP (adenosine triphosphate, an energy-carrying molecule of cells).

In addition, CNM-Au8 has antioxidant properties that may help to protect cells against oxidative stress.

Preclinical (in the lab) data showed that CNM-Au8 aided the survival of dopaminergic neurons, and helped prevent the loss of mitochondria.

In a rat model of Parkinson’s disease, treatment with CNM-Au8 improved the animal’s motor activity compared to control (untreated) mice. Of note, rats treated with CNM-Au8 in this test showed better results than did rats given carbidopa/levodopa, a standard Parkinson’s therapy.

“Our preclinical data with CNM-Au8 demonstrated improvements in neuronal bioenergetics, which may improve the survival of dopaminergic neurons in patients with PD [Parkinson’s disease], thereby helping slow the progression of this devastating disease,” Etherington said.

A Phase 1 clinical trial involving healthy volunteers (NCT02755870) found CNM-Au8 to be safe.

In the REPAIR-PD study, patients will first undergo a four-week screening period, after which they will drink two ounces of CNM-Au8 daily each morning for 12 weeks. Treatment will be followed by a four-week follow-up period.

The study’s primary outcome is to determine improvements in oxidative stress in the central nervous system (brain and spinal cord), assessed by the ratio of NAD+/NADH measured using magnetic resonance spectroscopy (MRS).

Additional (secondary) measures include assessing the effects of CNM-Au8 on energy production, and nerve cell metabolism.

“The objective of the REPAIR-PD Phase 2 study is to demonstrate improvements in brain bioenergetic metabolism in Parkinson’s disease patients treated with CNM-Au8. Participants will undergo 31phosphorous magnetic resonance spectroscopy (31P-MRS) imaging to show how treatment with CNM-Au8 results in improvements in brain metabolic and membrane biomarkers,” said Robert Glanzman, MD, chief medical officer of Clene.

Results from the REPAIR-PD trial are expected by mid-2020.

https://parkinsonsnewstoday.com/2019/12/06/dosting-starts-phase-2-trial-cnm-au8-potential-dopaminergic-neuron-therapy/

Exploring the Diversity of Parkinson's Proteins

Dec 05, 2019  Original story from the German Center for Neurodegenerative Diseases

Parkinson’s and multisystem atrophy (MSA) – both of them neurodegenerative diseases – are associated with the accumulation of alpha-synuclein proteins in the brain. Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the Max Planck Institute for Biophysical Chemistry (MPI-BPC) have investigated the molecular makeup of these protein deposits finding structural diversity. Experts from South Korea, Australia, and Argentina were also involved in the study. The results suggest that Parkinson’s might be related to diverse types of protein aggregates.

Alpha-synuclein is a protein that occurs naturally in the body. It is assumed to be involved in signal transmission between neurons. The protein appears both at the cell membrane and solved – floating, so to speak - in the cell’s interior. In addition to these “normal” variants, there are others that manifest in brain diseases. This applies e. g. to Parkinson’s disease and MSA. Both can be associated with various neurological impairments, including movement disorders. In Parkinson’s and MSA alpha-synuclein molecules stick together. As a result, elongated aggregates arise that are deposited inside neurons and other brain cells. “These deposits successively appear in various areas of the brain. They are a disease hallmark,” explains Prof. Markus Zweckstetter, who heads a research group at the DZNE and the MPI-BPC. “There is evidence that these aggregates are harmful to neurons and promote disease progression.”

A matter of folding

These deposits represent a potential starting point for medicines. The idea is that drugs might prevent alpha-synuclein molecules from sticking together or dissolve existing aggregates. To identify potential docking sites for agents, data on the aggregates’ fine structure is required. Thus, the question is: What kind of shape (also known as “folding”) do the molecules adopt within the aggregates? So far, information on this topic had been limited to data from laboratory experiments. “Previous studies investigated the molecular structure of aggregates that were synthesized in a test tube. We asked ourselves how well such artificially produced specimens reflect the patient’s situation. That is why we studied aggregates generated from tissue samples from patients,” said Zweckstetter. “We collaborated closely with international partners on this project. In fact, the tissue samples originated in Australia and the aggregates were synthesized in South Korea. We then did the structural studies in Göttingen.”

Aggregates from brain samples taken from five deceased Parkinson’s patients and five deceased MSA patients were examined. For comparison, the researchers artificially produced different variants of alpha-synuclein aggregates. For this, they used standard procedures. To compare the structure of the different aggregates, they applied nuclear magnetic resonance spectroscopy and other methods.

Structural differences

“We found that aggregated proteins that came from the lab were structurally different to all aggregates generated from patient material,” Dr. Timo Strohäker, first author of the study, commented on the findings. “In addition, proteins of MSA patients differed from those of Parkinson’s patients. If one looks at the data more closely, you notice that the proteins of the MSA patients all had a largely similar shape. The proteins of the patients with Parkinson’s were more heterogeneous. When comparing the proteins of individual Parkinson’s patients, there is a certain structural diversity.”

The alpha-synuclein proteins of all aggregates contain “beta sheets”, which is in line with previous investigations. Accordingly, the molecular backbone is twisted in a way that the proteins are largely two-dimensional. Within the aggregates, the proteins stick together in layers. However, folding does not encompass the whole protein. Each protein also contains areas that are unstructured. Besides, orientation of the beta sheets bears significance. “It is a question of how much of a protein is folded and also how it is folded,” Zweckstetter stated.

Various types of aggregates in Parkinson’s

In the structure of the alpha-synuclein associated with Parkinson’s, there were some significant differences between patients. This might be due to the fact that the course of Parkinson’s can vary quite considerably between individuals. “The variability of Parkinson’s disease could be related to differences in the folding of aggregated alpha-synuclein. This would be in contrast to the ‘one disease-one strain’ hypothesis, that is to say that Parkinson’s disease is associated with one, clearly defined aggregate form. However, in view of our relatively small sample of five patients, this is just a guess,” said Zweckstetter. “Yet, our results certainly prove that studies with tissue samples from patients are necessary to complement lab experiments in a sensible way.”

Reference

Strohäker et al. (2019) Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts. Nature Communications. DOI: https://doi.org/10.1038/s41467-019-13564-w

https://www.technologynetworks.com/neuroscience/news/exploring-the-diversity-of-parkinsons-proteins-328017

Patent Describes Apple Watch Feature for Improving Treatment of Parkinson's Disease Symptoms

December 5, 2019  by Tim Hardwick (Rumors)

A newly unearthed patent reveals that Apple is exploring how a future Apple Watch could help doctors monitor the symptoms of Parkinson's patients. 

Spotted by AppleInsider, "Passive Tracking of Dyskinesia/Tremor Symptoms" describes the use of special sensors in a proposed ‌Apple Watch‌ medical feature and the reasoning behind it. 

"There are an estimated 600,000 to 1 million cases of Parkinson's Disease in the United States and 60,000 new cases are diagnosed each year," reads the filing, which goes on to describe the symptoms sufferers have to live with. "Symptoms of PD include... tremor and dyskinesia. Dyskinesia is an uncontrollable and involuntary movement that can resemble twitching, fidgeting, swaying or bobbing."

The patent states that dyskinesia and tremors can occur when all of the other features of Parkinson's Disease are being managed through medication. Unfortunately, the dopamine replacement therapy can also cause more pronounced side effects, and doctors have to rely on in-clinic tests and patient reports to regulate their treatment effectively. 

"A patient's quality of life is largely dependent on how precisely clinicians titrate and schedule the patient's medications to minimize the patient's symptoms. This is a challenge for clinicians because each patient has a different combination of symptoms that can change and become more severe over time. Also, in any given day the symptoms may fluctuate based on medications, food intake, sleep, stress, exercise, etc."

The feature uses motion sensors to monitor the wearer's movement and the data gathered is analyzed on the device using the Unified Parkinson's Disease Rating Scale (UPDRS). According to Apple, this allows the data to be collected more reliably and means the sufferer doesn't need to keep close track of their symptoms and can better plan activities around symptom patterns. 

The image above shows a patient wearing an ‌Apple Watch‌, but the patient doesn't specify that the feature would be limited to a wrist-based device, suggesting it could make its way into an iPhone, or perhaps even an electronic finger ring.

https://www.macrumors.com/2019/12/05/patent-apple-watch-improving-parkinsons-symptoms/

Scientists identify chaperones as potential therapies for Parkinson's disease

 December 5, 2019       By Samantha Black, Ph.D.  

University of Basel, Biozentrum

Researchers from the University of Basel have identified the malfunctional relationship and master regulatory mechanisms between chaperone proteins and α-Synuclein occurring in Parkinson's disease. The findings were published in Nature on December 4.

Chaperones are proteins that assist with assembly and disassembly of other macromolecular structures. In humans, chaperones interact with α-Synuclein and the formation of aggregates of intrinsically disordered α-Synuclein, called Lewy bodies, which are strongly associated with Parkinson's disease.

Parkinson's disease is a debilitating neurodegenerative disorder with poorly understood causes. Some are genetic while others are a combination of environmental factors. Regardless of the cause, the disease leads to nerve death within the brain. But with the life expectancy rising around the world, the incidence of Parkinson's disease is projected to increase rapidly in the next years. Therefore, the need for effective therapies is crucial.

Molecular bodyguards interact with α-Synuclein

In the study, the researchers sought to systematically characterize the interaction of molecular chaperones with α-synuclein in vitro as well as in cells at the atomic level. In humans, there are only 30-40 chaperones that could potentially interact with α-Synuclein. They discovered six highly divergent molecular chaperones commonly recognize a canonical motif in α-synuclein and hinder the aggregation of α-synuclein.

"Using state-of-the-art NMR technology, we have discovered a specific pattern that determines the exact interaction site of α-Synuclein with chaperones," explains Sebastian Hiller. "There is not fixed, rigid interaction, but a dynamic and constantly changing encounter."

Impaired chaperone binding causes cell damage

In healthy cells, α-Synuclein is always accompanied by chaperones such that the protein always remains transportable and a pool of functional α-Synuclein proteins is available. Some post-translational modifications of α-Synuclein, such as those observed in Parkinson's disease can interfere with chaperone binding. The researchers found that transient membrane binding triggers a remarkable re-localization of α-synuclein to the mitochondria and concomitant formation of aggregates. Previous research shows that Lewy bodies mainly consist of mitochondrial membrane fragments of α-Synuclein.

New function for chaperones discovered

"With our work, we are questioning the paradigm that the function of chaperones is solely to help proteins to fold into their proper shape," says Hiller. "Chaperones do far more than just assist in protein folding. They control cellular processes by flexibly interacting with a variety of proteins and accompanying them like a shadow." This research helps gain a deeper understanding of the molecular role that chaperones play in cell function and can provide important clues for the development of novel therapies for Parkinson's disease.

https://www.scienceboard.net/index.aspx?sec=ser&sub=def&pag=dis&ItemID=381

Drug helped dementia patients curb their hallucinations and delusions

December 5, 2019

Nuplazid, a drug that treats psychosis in patients with Parkinson’s disease, also curbed hallucinations and delusions in people with dementia, researchers said this week at an Alzheimer’s conference in San Diego.

(Acadia Pharmaceuticals Inc. via Associated Press)

A drug that curbs delusions in Parkinson’s patients did the same for people with Alzheimer’s disease and other forms of dementia in a clinical trial that was stopped early because the benefit seemed clear.

If regulators agree, the drug could become the first offered specifically for treating dementia-related psychosis. It would also be the first new medicine for Alzheimer’s in nearly two decades. 

The daily pill targets some of the most troubling symptoms that patients and caregivers face — hallucinations that often lead to anxiety, aggression, and physical and verbal abuse.

Trial results were disclosed this week at an Alzheimer’s conference in  San Diego.

“This would be a very important advance,” said one independent expert, Dr. Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation.

Although the field is focused on finding a cure for dementia and preventing future cases, “there is a huge unmet need for better treatment” for those who have it now, said Maria Carrillo, chief science officer for the Alzheimer’s Assn.

The drug, pimavanserin, is sold as Nuplazid by Acadia Pharmaceuticals Inc. It was approved for Parkinson’s-related psychosis in 2016 and is thought to work by blocking a brain chemical that seems to spur delusions.

About 8 million Americans have dementia, and studies suggest that up to 30% of them develop psychosis.

“It’s terrifying,” said Dr. Jeffrey Cummings of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “You believe that people might be trying to hurt you. You believe that people are stealing from you. You believe that your spouse is unfaithful to you. Those are the three most common false beliefs.”

Cummings consults for Acadia and helped lead the study, which included about 400 people with dementia and psychosis. All were given a low dose of the drug for three months, and those who seemed to respond or benefit were then split into two groups. Half continued on the drug and the others were given dummy pills for six months or until they had a relapse or worsening of symptoms. Neither the patients nor their doctors knew who was getting what.

Independent monitors stopped the study when they saw that those on dummy pills were more than twice as likely as those on the drug to relapse or worsen — 28% versus nearly 13%.

There were relatively few serious side effects — 5% in the drug group and 4% in the others. Headaches and urinary tract infections were more common among those on the drug. Two deaths occurred, but study leaders said neither was related to the drug.

Carrillo said the study was small, but the drug’s effect seemed large. It’s unclear whether the federal Food and Drug Administration would want more evidence to approve a new use.

Current anti-psychotic medicines have some major drawbacks and are not approved for dementia patients.

“They’re often used off-label because we have very few other options,” Fillit said.

All carry warnings that they can raise the risk of death in elderly patients, as does Nuplazid.

The drug costs about $3,000 a month, so cost could be an issue. The amount patients pay can vary depending on insurance coverage.

https://www.latimes.com/science/story/2019-12-05/drug-can-curb-dementia-delusions

Parkinson’s Changes the Rules: It’s OK to Ask for Help

DECEMBER 5, 2019 By  Lori DePorter

We all have a fundamental desire to help our loved ones, and this is particularly true of those of us with early-onset Parkinson’s disease. Life moves along, and we try to advance with it. We are used to taking care of our responsibilities. But when we have Parkinson’s, the rules change.

I was trying to accomplish many things and not doing any of them well. I felt defeated in my job, and as a mom, daughter, and wife. I didn’t know how to step back and recognize my limitations. I had been taking care of everything for over 25 years and I loved it.

Now I find myself in unfamiliar territory. It may be a natural part of getting older or my progression, but I am not the same person. I can’t do everything that I could in the past. And accepting my limitations is not easy.

When my doctor suggested that I see a psychologist, my immediate reaction was, “No, I don’t need to.” However, she was right. I did need therapy, at least in the short term. While it is not for everyone, therapy has been beneficial when I find myself struggling. My therapist can make me aware of things that my friends, family, and others who are part of my everyday routine can’t see in me.

Talking with a professional provides a different perspective. And sometimes, having a fresh look at your situation can help you to get to where you want to be. Unfortunately, therapy is not always available, and people often avoid seeking this kind of help because of the stigma attached.

New rules

While my approach is still a work in progress, I have developed some new rules. I am sure that I will add more and you may have some rules of your own. With the busy holiday season approaching, you may want to give these a try:

• You don’t need to take care of everything.
• Know when to seek support.
• It’s OK to ask for assistance.
• Allow others to help.

Parkinson’s makes us feel helpless at times. However, it’s not just about us. What about the people in our lives? Do they feel the same way? Maybe playing by the new rules and allowing them to help us will make them feel more useful. We can see our acceptance of their help as a gift to them rather than a burden — something as simple as opening a car door can make all the difference.

***

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/2019/12/05/changes-rules-accepting-help-counseling-psychotherapy/

Exposure to Second-Hand Smoke Linked to Lower Risk of Developing Parkinson’s, Study Suggests

DECEMBER 5, 2019 BY CATARINA SILVA, MSC

Second-hand smoke may have a neuroprotective effect, as exposure to this type of indoor pollutant seems to be associated with a decreased risk of developing Parkinson’s disease, according to a recent study.

Conversely, exposure to certain air pollutants — like nitrogen dioxide and ozone — might contribute to a higher risk of developing the disease.

The study, “The impact of long-term exposure to ambient air pollution and second-hand smoke on the onset of Parkinson disease: a review and meta-analysis,” was published in Public Health.

Air pollution is composed of a variety of particulate air pollutants, volatile organic compounds, gaseous air pollutants, and airborne metals. Exposure to polluted air has been consistently associated with adverse effects in respiratory and cardiovascular diseases, but little is known about the effects of such exposure in neurodegenerative disorders such as Parkinson’s.

Although the exact causes behind Parkinson’s disease are not fully understood, it is thought to be induced by “a complicated interplay of environmental and genetic factors,” according to these researchers.

As such, “further investigation of the modifiable risk factors of [Parkinson’s disease] is of imperative significance and expected to have broad implication for the primordial prevention of this disease,” they said.

Second-hand smoke is a type of indoor air pollution. Evidence indicates that active smokers have a 50% lower chance of developing Parkinson’s in comparison with non-smokers. “However, whether this negative correlation is causal and persists among persons regularly exposed to SS [second-hand smoke] remains undetermined,” the researchers said.

To learn more, the scientists searched five medicine-related databases for any observational or epidemiological evidence on the relationship between long-term exposure to air pollution and second-hand smoke and Parkinson’s susceptibility.

The studied air pollutants included: particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), such as combustion particles, organic compounds, and metals; particulate matter with less 10 μm in diameter (PM10), including dust, pollen, and mold; nitrogen dioxides (NO2); ozone (O3); and carbon monoxide.

The researchers combined the results of 21 studies, involving a total 222,051 Parkinson’s patients, and performed a statistical review known as a meta-analysis.

A marginally significant higher risk of developing Parkinson’s disease was observed in those exposed to PM2.5, NO2, and O3. Although carbon monoxide was found to be positively associated with Parkinson’s susceptibility, statistical significance was not attained.

“Second-hand smoke conferred reduced risk of Parkinson disease, regardless of exposure occasions [at home/at work/in children] and timing,” the researchers said. This suggests that second-hand smoke might have a neuroprotective effect in those who are susceptible to developing Parkinson’s at some point in their lives.

Some possible explanations exist as to why cigarette smoke may be associated with a lower risk of Parkinson’s. One theory is that some tobacco smoke compounds contain properties that inhibit monoamine oxidase (MAO), an enzyme that plays a key role in the activation of MPTP, a well-known Parkinson’s-inducing neurotoxin, and that is involved in the degradation process of dopamine released by nerve cells.

“Other hypotheses include the direct neuroprotective effect of nicotine by stimulating dopamine release, upregulating nicotinic receptors, and inhibiting alpha-synuclein fibrillation, thereby suppressing and relieving parkinsonian symptoms,” the researchers said.

Given the many harmful effects of air pollutants, public and environmental health strategies that reduce outdoor air pollution levels could help lower the burden of Parkinson’s disease.

Despite the potential neuroprotective effect of second-hand smoke, caution is advised when interpreting these results, as more large-scale studies are necessary to fully understand such an association.

https://parkinsonsnewstoday.com/2019/12/05/second-hand-smoke-associated-with-lower-risk-developing-parkinsons/

Aphios Granted US Patent for Oral Administration of Bryostatin-1 Nanoparticles for Treatment of Neurodegenerative Diseases

December 05, 2019

WOBURN, Mass.--(BUSINESS WIRE)--Aphios Corporation today announced that it was granted United States Patent No. 10,485,766 for the oral administration of Bryostatin-1 nanoparticles for the treatment of neurodegenerative diseases such as Huntington’s Disease, Parkinson's disease, Multiple Sclerosis, Down syndrome and Alzheimer's disease.

Bryostatin-1 nanoparticles rapidly restore cognitive performance in Alzheimer's transgenic mice and improve inter-trial latency in transgenic mouse model of Down syndrome which shares many characteristics with Alzheimer’s

Neurodegenerative diseases, such as Down syndrome, Alzheimer’s disease, and other spongiform encephalopathies remain major health problems. Currently there are very limited means to treat these diseases. With respect to Alzheimer’s, Huntington’s and Parkinson’s diseases, these diseases tend to manifest themselves in older individuals and as the diseases progress; the afflicted individuals are less able to care for themselves. Dr. Trevor P. Castor, co-inventor of the patent states that, “It is therefore highly desirable to have simple therapies which can be administered (e.g. oral formulations) without the need for specially trained healthcare providers.”

Dr. Castor continues, “Our Mechanism-of-Action studies have shown that our lead Alzheimer's disease drug candidate, APH-1104, a potent analog of Bryostatin-1, is neuroprotective by α-secretase activation via novel PKC isoforms, down-regulation of pro-inflammatory and angiogenic processes and the substitution of β-amyloid for its soluble and harmless relative, sAPP-α at concentrations which are orders of magnitude lower than conventional APP modulators. Our in vivo studies show that we can rapidly restore cognitive performance in AD-transgenic mice by oral administration of Bryostatin-1 encapsulated in biodegradable polymer nanospheres. These nanoparticles protect Bryostatin-1 in its transit to the stomach, are resistant to stomach acids, and increase residence time and efficacy once transported to the circulation system in the duodenum.”

Dr. Jonathan Steven Alexander, a professor in LSU Health Shreveport’s Department of Molecular and Cellular Physiology and a co-inventor of the patent states, “We are another step closer to helping find a treatment for Alzheimer’s disease and other neurodegenerative diseases. In our hands, we discovered that Bryostatin-1 improves inter-trial latency in a transgenic mouse model of Down syndrome. Bryostatin-1 showed a significant improvement in inter-trial water maze performance, with a p<0.001 compared to vehicle treated transgenic Down mice. This shows a significant difference in task acquisition in the Down syndrome model which shares many characteristics with Alzheimer’s disease. Importantly, these data show for the first time a dose dependent improvement in task performance.” 

About LSU Health Shreveport: LSU Health Sciences Center Shreveport is home to the School of Medicine, School of Graduate Studies and School of Allied Health Professions. The primary mission of the LSU’s Health Sciences Center at Shreveport is to teach, heal, and discover, in order to advance the well-being of the region and beyond. At the heart of LSUHSC-S is a strong faculty that includes over 600 nationally and internationally-acclaimed physicians and scientists. LSU Health Shreveport has strong community support, fostering a culture of diversity and inclusion that promotes mutual respect for all. For more information, visit www.lsuhscshreveport.edu.

About Aphios Corporation: Aphios Corporation (www.aphios.com) is an emerging growth biotechnology company developing green enabling technology platforms for improving drug discovery and manufacturing, nanotechnology drug delivery and pathogenic drug safety. Based on these enabling technology platforms, we are developing enhanced therapeutics for health maintenance and disease prevention, and the treatment of cancers such as prostate and pancreatic cancer, supportive care such as CINV, infectious diseases such as HIV, and nervous system disorders such as Alzheimer’s Disease, Multiple Sclerosis, Pain and Opioid Addiction.

Research leading to this discovery was in part funded by a SBIR Grant No. No. 5R44AG034760-03 from the National Institute on Aging (NIA), National Institutes of Health (NIH). The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of NIA and NIH.

https://www.businesswire.com/news/home/20191205005233/en/Aphios-Granted-Patent-Oral-Administration-Bryostatin-1-Nanoparticles

Though safe, nilotinib does not show promise for benefit for Parkinson's disease

DECEMBER 5, 2019   by Northwestern University

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Northwestern University and the Parkinson Study Group announced that the Nilotinib in Parkinson's Disease (NILO-PD) study showed that nilotinib, an FDA-approved treatment for chronic myelogenous leukemia being tested for potential repurposing as a Parkinson's drug, was safe and tolerable in its trial population of 76 participants with moderate to advanced Parkinson's but does not exert a clinically meaningful benefit or biological effect to benefit those with Parkinson's disease.

The NILO-PD Steering Committee unanimously agreed to accelerate the announcement of these results, originally planned for 2020, in line with members' commitment to keep the Parkinson's community informed of new scientific findings as quickly as possible.

Gary Rafaloff of Marlboro, New Jersey, diagnosed with Parkinson's in 2012, served as a member of the NILO-PD steering committee. "No one wanted this trial to succeed more than I did," Rafaloff said. "If I had qualified, I would have participated as a volunteer. Instead I spent over two years working with the other committee members to ensure that the trial was designed and administered with the utmost rigor. Nevertheless, the results are what they are. The good news is that there are several other upcoming trials that we can focus on as we look forward to future success."

The randomized, placebo-controlled, double-blind study was led by principal investigator Tanya Simuni, MD, professor of neurology and head of the division of movement disorders at Northwestern University Feinberg School of Medicine. It was carried out at 25 sites through the Parkinson Study Group, the largest not-for-profit scientific network of Parkinson's disease centers in North America.

The trial was coordinated through the Clinical Trial Coordination Center at the University of Rochester, and statistical analysis was led by the University of Iowa. NILO-PD—which tested placebo, 150mg and 300mg doses of nilotinib daily over six months—was supported by an international consortium of research and patient advocacy groups: The Michael J. Fox Foundation for Parkinson's Research, The Cure Parkinson's Trust (London, United Kingdom), Van Andel Institute, The Parkinson Alliance and the Demoucelle Parkinson Charity (Brussels, Belgium). Novartis Pharmaceuticals Corporation provided the study drug and placebo for use in the trial.

"Science is a high-risk endeavor and too often strategies, even promising ones, do not prove replicable or scalable. Unfortunately, the results we observed—as measured by change in clinical symptoms and influence on biological measures—did not support testing nilotinib in a larger study," Simuni said. "This is not the outcome we hoped for, but we remain dedicated to pursuing better treatments by advancing other potential therapies in today's robust Parkinson's pipeline."

Simuni noted that it is critical that anyone considering adding nilotinib to their Parkinson's treatment regimen work closely with their health care provider before doing so. While nilotinib was seen to be safe and tolerable in the study population, the study was strict with health history, excluding those who may have heart issues or other health challenges. Therefore, its safety in a broader Parkinson's population remains unproven.

Nilotinib (marketed as Tasigna) inhibits the activity of c-Abl, a protein that has been linked to cellular pathways associated with Parkinson's disease including aggregation of alpha-synuclein protein and deactivation of parkin protein. In 2016, preliminary data from a small open-label Phase I clinical trial evaluating the safety and tolerability of nilotinib in people with advanced Parkinson's showed potential benefit in PD. The c-Abl pathway remains an important target of interest to Parkinson's researchers, with trials of other drugs in this class ongoing.

Study results were unblinded at a steering committee meeting on November 15. Study leadership and funding partners committed to broadly sharing top-line findings on an accelerated timeline—after reporting high-level results back to study participants and site investigators—in service to the Parkinson's community awaiting news from this trial and the donors who made the study possible.

NILO-PD leaders will share more detailed data with study volunteers on a call on December 12 and with the scientific community in February at the 3rd Pan American Parkinson's Disease and Movement Disorders Congress in Miami, Florida. The partners also plan to make data and biosamples available for further analysis to the wider Parkinson's research community.

"When the science doesn't pan out, it's easy to feel deflated. As a patient, I get it," said Michael J. Fox. "But even a study that doesn't show the results we hoped for ultimately gets us closer to the one that will."

Provided by Northwestern University

https://medicalxpress.com/news/2019-12-safe-nilotinib-benefit-parkinson-disease.html