“Mushroom Alcohol”, Neurodegeneration and PARKINSON’S DISEASE

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“Mushroom Alcohol”, Neurodegeneration and PARKINSON’S DISEASE

During Hurricane Katrina, researcher Joan Bennett lived in New Orleans and worked at Tulane University.  Her home was flooded by the hurricane and during the clean up period, she was plagued with headaches, nausea and dizziness.  Her work was as a scientist, and specifically as a plant pathologist, so she collected samples of the molds she found wearing appropriate protective gear and masks and gloves. A bit later, she transferred her job to Rutgers.

There, she met Arati Inamdar, Ph.D., who is a researcher in the School of Environmental and Biological Sciences at Rutgers.  Together, they began testing Bennett’s samples of mold in hopes of finding why Bennett had been sickened after Katrina.  They discovered that those mold samples contained a volatile organic compound known as 1-octen-3-ol, that is also known commonly as mushroom alcohol.  They exposed fruit flies to this compound and found that they developed movement disorders similar to the disorders caused by pesticides such as rotenone or paraquat.  Further testing showed that 1-octen-3-ol caused loss of dopamine in two specific genes that lead to a loss of neurons and the development of Parkinson’s like symptoms.

“Parkinson’s has been linked to exposure to environmental toxins, but the toxins were man-made chemicals,” said Inamdar.  “In this paper, we show that biologic compounds have the potential to damage dopamine and cause Parkinson’s symptoms.”  Many new studies show that Parkinson’s disease is increasing in rural areas, but is often thought to be from exposure to pesticides.  Rural areas also have high rates of mold and mushroom exposure.  Now there is the possibility that for people with a genetic predisposition, molds and volatile compounds that are produced by molds and fungus may also lead to the development of symptoms like PARKINSON’S DISEASE.

As with most research projects, this work was accomplished by a team.  On this team were Muhammad Hossein, Jason Richardson, Alison Bernstein and Gary Miller.  Their paper was published this week in the journal Proceedings of the National Academy of Sciences..

 

Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration

Arati A. Inamdar,Muhammad M. Hossain, Alison I. Bernstein, Gary W. Miller, Jason R. Richardson,and Joan Wennstrom Bennett PNAS 2013 ; published ahead of print November 11, 2013, doi:10.1073/pnas.1318830110

 

Review by Marcia McCall

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Pimavanserin Relieves Psychosis in PARKINSON’S DISEASE

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The result of a Phase III study that was released on November 1, 2013 demonstrated that Pimavanserin was effective in relieving symptoms of psychosis in people with PARKINSON’S DISEASE without worsening the other symptoms of the disease.  Pimavanserin is a new type of anti-psychotic drug that works by blocking the receptors for serotonin in areas of the brain that connect sensory perceptions and conscious thoughts.

Psychosis in people with PARKINSON’S DISEASE is not an uncommon occurrence.  It is a very serious issue that makes caregiving in the home nearly impossible and results in the admission of people with PARKINSON’S DISEASE to long term care facilities where they can be monitored day and night.  Prognosis is not good, and often marks the beginning of serious decline.

Hallucinations usually manifest as rather benign hallucinations, often of children or  seeing “little people”, but can sometimes be much more serious with visions of malevolent intruders or assume sexual overtones.  Long time use of anti-parkinson’s medications, such as levodopa replacement therapies is thought to be at least part of the cause as well as the disease pathology itself.  Sleep disturbances are also a major contributor to psychotic symptoms.  Newer studies have shown there are other irregularities in the white matter fibers of the brain that also contribute to psychoses in people with PARKINSON’S DISEASE, but whether the damage to white matter fibers is caused by the disease or contributes to the disease has not been clearly elucidated.

Neurologists’ usual response to hallucinations is to reduce levodopa to the lowest effective dose possible, and if that does not solve the problem, then to introduce antipsychotic medications.  Seroquel (quetiapine) is often the first drug of choice, but clinical trials have shown very limited benefit.  Clozaril is also a possible candidate, however it requires bi-weekly blood draws to monitor liver function, a major drawback for the already compromised lives of people with PARKINSON’S DISEASE.  Anti-depressants have sometimes shown good results, and certain anti cholinergic medications have also sometimes been effective, but side effects have been problematic.

Pimavanserin has been developed by the pharmaceutical company Acadia.  The Food and Drug Administration has agreed that the studies thus far conducted have been favorable and they are allowing Acadia to go forward with filing a New Drug Application.  A few more supportive studies must be undertaken before approval can be granted, but the company is focused on moving ahead to obtain FDA approval as quickly as possible.

 

News release from Acadia Pharmaceuticals

 

Article by Marcia McCall

 

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January 2014 Educational Conference

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PARKINSON RESEARCH FOUNDATION

Cordially Invites You to Attend Our

2014 Educational Conference for Patients, Caregivers & Community

BeYourBest

BE YOUR BEST

                                  With Parkinson’s!

FRIDAY, JANUARY 10, 2014 

Registration & Continental Breakfast: 9:30am ● Program: 10am-2pm

 

PARKINSON PLACE

5969 Cattleridge Blvd., Suite 100, Sarasota, FL. 34232

Continental Breakfast & Lunch Provided

$15 per person ● Scholarships Available

Agenda

“Overview of Parkinson’s Disease and Newer Drugs in the Pipeline”

Juan Sanchez-Ramos, MD, PhD – Fellowship Trained Movement Disorders Specialist
Director, USF Parkinson Clinic at Parkinson Place, PRF Medical Director

 

“Non-Motor Symptoms of Parkinson’s Disease: Cognition and Behavior”

Patrick J. Madden, MD – Director, Neurology Clinic at Parkinson Place

 

“Stem Cell Treatment for Parkinson’s Disease”

James M. Schumacher, MD – Neuroregeneration Institute, Harvard Medical School

 

“Three Steps to a Better Life with Parkinson’s”

Marilyn J. Tait – Parkinson Educator, Motivator & Advocate; PRF Executive Director

SPACE IS LIMITED ● RESERVATIONS REQUIRED

TONI GOIN – 941.893.4188 – TGoin@ParkinsonResearchFoundation.org

 

PREPAY FOR TICKETS ONLINE

https://www.eventbrite.com/e/be-your-best-with-parkinsons-tickets-9395776019

                        ParkinsonResearchFoundation.org

Two Forms of Alpha-Synuclein; Two Forms of PARKINSON’S DISEASE

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Two different laboratories of researchers, one in France and one in the U.S. have found that alpha-synuclein, while the same biologically and molecularly, can form two distinct types of forms or strains, which perhaps explains why people with PARKINSON’S DISEASE experience such different symptoms.

The French team from the Laboratoire CNRS d’Enzymologie et Biochime Structurales published their paper on October 10 in the Journal Nature Communications.  This team identified two distinct shapes for the aggregates of alpha synuclein, one is round, “spaghetti” like and the other is flat, “linguini” like.  The spaghetti shape is much more toxic, rapidly penetrating and ultimately killing the cells in the brain.  It is very resistant to cell chemistry that would normally be able to eliminate unwanted intruders, such as viruses or other destructive proteins.  Linguini forms on the other hand, are more easily controlled by the cell and become toxic to the cell much more slowly.

This team thinks that the differences in the shapes of the aggregates may be responsible for the differences in the symptoms of PARKINSON’S DISEASE between those that are primarily motor affected, such as tremor, and those that are cognitive or behavioral.  While they are continuing to refine their research and better characterize the structures of alpha-synuclein, they believe that this process could lead to a targeted therapeutic treatment specific to each strain.

In the US, a team led by Virginia Lee and John Q. Trojanowski, two esteemed researchers in PARKINSON’S DISEASE from the Perelman School of Medicine at the University of Pennsylvania,  have discovered that alpha-synuclein can take on two different forms despite having the same chemical make up and interact with other disease proteins found in Alzheimer’s, PARKINSON’S and other neurodegenerative disease.

Tau protein is a marker of Alzheimer’s and alpha-synuclein is a marker for PARKINSON’S.  Post mortem brains of people with PARKINSON’S who had symptoms of cognitive decline or dementia showed both tau and alpha-synuclein closely entwined. Brains of patients that did not have dementia also has aggregates of alpha-synuclein, but the shape of the protein was different.  This could correspond to the “spaghetti” and “linguini” models.  However, Lee and Trojanowski found that over time, this strain  could change into the more fibril type found with the dementia, but it took longer for it to become entangled with tau. They speculate that these different shapes assumed by alpha-synuclein may be responsible for the different symptoms observed in different PARKINSON’S DISEASE patients, why some patients have more motor symptoms and others are affected with more cognitive decline or dementia.

More research is needed to validate and explore these findings more clearly.  But it also could lead to more therapeutic targets for treatment.  If each strain can be clearly defined, it can be selectively targeted by antibodies designed specifically for each strain.  Lee says “What we’ve found opens up new areas for developing therapies and particularly immunotherapies for PARKINSON’S and other neurodegenerative diseases.”

 

 

 

Luc Bousset, Laura Pieri, Gemma Ruiz-Arlandis, Julia Gath, Poul Henning Jensen, + et al. Structural and functional characterization of two alpha-synuclein strains  Nature Communications 4, doi:10.1038/ncomms3575

Jing L. Guo, Dustin J. Covell, Joshua P. Daniels, Michiyo Iba, Anna Stieber, Bin Zhang, Dawn M. Riddle, Linda K. Kwong, Yan Xu, John Q. Trojanowski, Virginia M.Y. Lee  Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons Cell: 3July2013; 154:1

 

Review by Marcia McCall

 

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A Test to Determine Rate of Dopamine Loss in PARKINSON’S DISEASE

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Loss of dopamine in neurons is a given in the cause of PARKINSON’S DISEASE, but there has been no non-invasive way to measure how much dopamine has been lost or what the rate of dopamine loss might be.  Clinical treatment and dopamine replacement therapies could be made more exact if this could be determined.

A team of investigators from the Cognitive Aging Laboratory at Georgetown University have devised a test that may help neurologists determine the amounts of dopamine lost  on an individual basis for people with PARKINSON’S DISEASE.  It is an amazingly simple test, but the early small study has shown good results.

The Triplet-Learning Task (TLT) was developed by Katherine R. Gamble, who is a psychology student working on a Ph.D. Her senior investigator is Darlene Howard, Ph.D. .  It is based on implicit learning, a type of learning that occurs without awareness.  The brain region that is involved in implicit learning is the caudate nucleus, which is also affected by the loss of dopamine in PARKINSON’S DISEASE..

The test does not involve any complex motor skills: it is a sequential learning task.  Subjects are shown four open circles and two red dots.  They are asked to respond when a green dot appears.  After a bit of practice, subjects quickly learn how to determine where that green dot will appear and their response time become fasters and their responses more accurate.  However, with a loss of dopamine, response time becomes slower and accuracy falters.    This may prove to be a valuable, non-invasive test to help neurologists determine what stage of the disease process the patient is experiencing  or to measure if the amount of dopamine replacement is adequate or effective.

 

 

Georgetown University Medical Center (2013, November 9). Simple dot test may help gauge progression of dopamine loss in Parkinson’s disease. ScienceDaily. Retrieved November 12, 2013, from http://www.sciencedaily.com­/releases/2013/11/131109192838.htm

 

Review by Marcia McCall

 

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Laser Therapy a New Hope for PARKINSON’S DISEASE

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Aggregates of alpha-synuclein in brain cells of people with PARKINSON’S DISEASE have long been the target of research hoping to cure or at least alleviate the symptoms of dementias often associated with PARKINSON’S DISEASE.  Newly publicized research from Chalmers University of Technology in Sweden together with Wroclaw University of Technology in Warsaw, Poland found that it is possible to use a laser driven technology to distinguish the formations of alpha-synuclein proteins from the formations of other functionally beneficial and necessary proteins in the brain.  The same technique, called “multi-photon laser technique” could also be used to eliminate those aggregated proteins..

These researchers believe that the ability to target these misfolded proteins that are believed to be part of the disease process for many dementia type diseases, including Alzheimer’s, PARKINSON’S,  and Lewy Body diseases may enable them to be destroyed by laser instead of by taking multiple drugs to counter their activity.  Photo acoustic therapies, such as these researchers discuss, has already been used to destroy cancer tumors in certain specific settings.  During this therapy, the specific light wave energy of the laser is converted to heat on targeted specific light wave sensitive receptors on the cells.  The heat generated then destroys that targeted cell.

This treatment for destroying alpha-synuclein misfolded proteins is a very new, “on the cutting edge of research” technology.  As with all new procedures and technologies, a lot of studies will need to be done before it can be made widely available to treat people with PARKINSON’S DISEASE.  It would be a non-surgically invasive procedure and would potentially reduce the use of medications while wiping out the dementia caused by accumulations of alpha-synuclein.

With Thanks to

Piotr Hanczyc, Marek Samoc, Bengt Norden. Multiphoton absorption in amyloid protein fibresNature Photonics, 2013; DOI: 10.1038/nphoton.2013.282

 

Reviewed by Marcia McCall

 

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Modern Versus Ancient Treatment for PARKINSON’S DISEASE

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PARKINSON’S DISEASE is a serious and complex neurodegenerative disease that has wide ranging effects.  The tremors, stiffness and rigidity and the slowness that PARKINSON’S DISEASE brings to the body of the affected person extends to the intellectual, emotional and social domains, too.  Every aspect of the person’s life feels the impact of this disease, and then that impact affects the people with whom that person associates.

Western modern medicine excels in attempting to treat the physiological symptoms, but is not so excellent at treating the well being of the affected person.  And therein lies a major challenge for the treatment of PARKINSON’S DISEASE.  Western medicine prides itself for being scientific and objective.  It sees diseases as discreet entities with specific causes that if eliminated or repaired will restore the body to health and thus the patient will be cured.  Diagnosis is about naming the cause and thereby providing a target at which treatment is directed and the patient becomes simply the location where that target resides.  This paradigm grants incredible authority and power to the physician and diminishes the involvement of the patient.  The elevation of technology in Western culture, with its own technological language, spoken only by “specialists” wearing white coats working with specialized high-tech medical machines really renders the patient helpless to understand what is going on and limits their ability to be involved in their own physical processes.

Modern medicine seems like a powerful miracle enacted upon the body of the patient…disease is primarily a bodily dysfunction, and it must be fought and conquered.  Even the language used to describe this is language of war…the disease causing entities (cells, virus, bacteria) are seen as “invaders” that “trigger” “waves” of reactions and  ”attack” the body’s ability to “combat” the disease”.  Research is looking for the “magic bullet”, the nation fights the “war on drugs”, people affected with a virus are “innocent victims”.

Focus of Western medicine is based on biology and chemistry…the “hard” sciences.  It is a simplification that splits the body from the mind, the disease from the patient and allows for more focus on “data”.  If “symptoms” do not show a cause in laboratory tests, imaging studies or with other “diagnostic” tools,  and if all tests are normal, then “nothing” must be wrong, or if something unusual does show up, then it is “abnormal”.  In fact, here in the United States, we have become obsessed with tracking our bodies’ functions…the use of individual blood pressure monitors, blood sugar monitors, pedometers, even “apps” on phones to remind us to record what we ate, when, or even to tell us when to do what!  We have become skilled at examining the “abnormal” symptoms of normal.

This simplification that splits body from mind has some serious consequences.  If the tests are “normal” and “nothing is wrong”, then the patient must be “imagining things”.  If it cannot be objectified or quantified it must not be “real”, or it exists only in the mind.   Only the body gets to have “real” illnesses, everything else then seems less real and possibly reflects a “character defect” or some lapse of self discipline in managing one’s emotions. This dual vision, this body/mind split is an illusion.  The body and the mind are not an either/or proposition.  This illusion is what is not real.

Today, many Western physicians recognize the oversimplification of the body/mind split, but find it very difficult to integrate into clinical practices that demand limited face to face time with a patient and expect detailed dictations.  Cultural differences have been acknowledged and the fact that cultural contexts can define how a patient understands disease.  But it is not just the culture of the patient that affects the treatment, it may also be the culture of the physician who is dispensing it.  The physician may be well trained in Western scientific medicine, but that physician also comes from a world or cultural experience that influences his/her world view and relationship to the patient.

Another area that separates the patient from their disease is the new trend and requirements for digitized records and making a person’s health information available to multiple points in diagnostic and treatment facilities.  Having a patient’s complete medical record at hand may assure more comprehensive treatment for the patient while simplifying the treatment process for the professionals involved.  But the patient as a person can feel somewhat abandoned and secondary to the professional’s attention to the computer and the need to enter every detail into the record.

PARKINSON’S DISEASE has been around for thousands of years.  It has been described in the literatures of nearly every civilization.  While today there exist many modern medicines that help treat the symptoms of this disease, there is still no known cure.  In those years before the advent of modern medicine, people found many ways to treat  and deal with this disease. They were no more able to cure the disease than modern medicine is today, yet people sought and responded to the treatments prescribed, which may or may not have been as effective as today’s treatments.  What benefit they offered perhaps came from treating the patient as a whole person, not limiting treatment to only the symptoms of the disease.

The allure of culturally alternative medicine is often that it gives the patient a measure of control over their treatment process.  It values the mind as much as the body and tries to integrate them in a more balanced approach.  Traditional Chinese or Ayurvedic medicines take into consideration a patient’s whole situation, their personal relationship, social standing, occupational, financial, familial situations.  Other cultures value the association of emotional states or experiences with physical symptoms. Symptoms are not simply data, but part of the person’s lived experience and how those symptoms are expressed and experienced are as much a part of the healing process as are the drugs and therapies used to treat them.  And, indeed, what is today modern medicine grew out the roots these sometimes ancient, but basic  practices of human wellness techniques.

 

Marcia McCall

 

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New Drugs for Parkinson’s Disease Under Development

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Lundbeck Pharmaceuticals is working on developing two new drugs to treat PARKINSON’S DISEASE from two different perspectives and they have received a large grant to help fund this promising research.

The first approach is directed at eliminating or at least preventing alpha synuclein from entering the nervous system.  Presently, Lundbeck has developed a line of anti-bodies that bind with alpha-synuclein and one those anti-bodies has shown a direct effect in animal models of PARKINSON’S DISEASE.  Their hope is to develop the best antibody with the potential to slow the progression of PARKINSON’S DISEASE in people or to perhaps, eliminate it altogether.  A human medical model is still a ways off, and lots of work remains to be done, but this company is definitely up to the task.

Their next project involves creating a symptomatic treatment that does not involve the dopamine receptors in the brain.  They are focused on a so-called “orphan G-protein” in a part of the brain that controls the motor system.  Already they have several drugs that can control the activity of this protein.  Their hope for this project is to create a new type of drug for treatment of the motor symptoms of PARKINSON’S DISEASE that does not have the side effects of current medications.  We all hope that success comes SOON!

Learn more about Lundbeck Research and Development

Review by Marcia McCall

Implant to Help Slow PARKINSON’S DISEASE

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Dr. Steven Gill has been researching the benefits of Glial-cell line Derived Neurotrophic Factor (GDNF)  in PARKINSON’S DISEASE for many years.

Together with his team of researchers from Frenchay Hospital in Bristol, United Kingdom, he had developed a new implant device to deliver GDNF directly to the affected area of the brain.

GDNF has been shown to be an especially potent factor for dopaminergic cell survival and for improving motor deficits such as those seen in PARKINSON’S DISEASE.

Finding ways to deliver GDNF to the affected areas in appropriate ways has been the challenge

The new device developed by this team consists of a small port surgically implanted behind the patient’s ear.

From this port, a system of tubes connects to the basal ganglia and regulated dose of GDNF can be pumped directly to the brain once a month.

To date, six patients have undergone this treatment and the team is now recruiting 36 more patients for a new trial.

If this treatment technology proves successful and safe, many other neurological diseases will be able to benefit from this technique.

Review by Marcia McCall

 

 

 

review by Marcia McCall

Highlights From the World Parkinson Congress 2013

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Memory and Mood Program Presented at the 2013 Parkinson’s World Conference

Sarah K. Lageman, Ph.D., from the Virginia Commonwealth University, Richmond, VA Speaking at the Montreal 2013 World Parkinson’s Conference, presented an abstract of a program she developed with her colleagues that helps people with PARKINSON’S DISEASE enhance their memory and improve their problem solving skills.  Cognitive impairment is one of the biggest obstacles to independent living faced by people with PARKINSON’S DISEASE.  In this small study, participants met once a week and learned practical techniques to help their memory, such as writing in a memory book and using a calendar along with problem solving steps. They also were part of a support group that was client centered where they could share their frustrations and techniques.  Although the numbers in this study are small, the improvements have been large.  “If a neurocognitive program can help keep people functioning better at least for a couple of years, that’s a benefit”, said Dr. Lageman.

 

Mood and Sociability Presented at the 2013 Parkinson’s World Conference

Susan Spear Bassett, Ph.D. from Johns Hopkins spoke at her poster presentation about depression and social involvement in PARKINSON’S DISEASE.  She and her colleagues conducted a study with 101 people with PARKINSON’S DISEASE who did not have dementia to examine the changes in social function caused by the disease.  They found that cognitive impairments along with depression contributed more to social withdrawal than the motor or movement symptoms of PARKINSON’S DISEASE.  Depression, loss of verbal skills and loss of fine motor skills all contributed to loss of social function, but management of depression did more to improve the quality of life and help social involvement.

 

Falls, Cognition and Gait Presented at the 2013 Parkinson’s World Conference

What are the factors that increase the likelihood that people newly diagnosed with PARKINSON’S DISEASE will fall frequently?   Lynn Rochester, Ph.D. and her team enrolled 94 newly diagnosed people with PARKINSON’S who had never fallen. and followed them for a year.  They wanted to know why some people fall more frequently than others.  Subjects were asked to keep a diary of their falls and underwent testing in several domains over the course of the study.  Findings showed that gait was of major importance.  Step time, speed, and distance of steps as well as the thinking about walking were major predictors of falling.  People who had fallen several times also had less confidence in their ability.  Measurement scales included the Unified Parkinson’s Disease Rating Scale, and the Postural Instability and Gait Disorder that is a sub-scale of the UPDRS, the Hoehn and Yahr Progression Scale, Strength ratings and several cognitive testing scales.  Work for this abstract was done at Newcastle University in Newcastle upon Tyne, England.

 

Parkinson Research Foundation’s Parkinson Place
Parkinson Place - Good Days Start Here
Parkinson Place started in September of 2012 has implemented many of the programs discussed at Montreal and more!  If you want to get a taste of what is going on at Parkinson Place please visit the website www.parkinsonplace.org.  The mission of the Parkinson Research Foundation is to assist in finding a cure for Parkinson’s disease and improving the lives of those living with the disease right now.  Parkinson Place is a Pilot project that has proved very successful creating a one stop shop for everything you need to live well with Parkinson’s.  Many support groups are now starting a “place” of their own using the format and videos from the site.  Come see why we are smiling at Parkinson Place!

 

All abstracts are from the World Parkinson Congress, Montreal, Quebec, Canada.

3.  Gaina, B. et al “motor, cognitive and affective characteristics of new fallers compared to non-fallers in an incident cohort of Parkinson’s disease” WPC 2013 Abstract 13:05

2.  Bassett, S. et al, “Impact of Parkinson’s disease on social role function: multifaceted disability” WPC 2013

1. Lageman, S. et al; “Initial Results of a randomized clinical trial comparing a neurocognitive intervention to supportive therapy in individuals with Parkinson’s disease” WPC 2013; Abstract 15:11

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