Wellness: Finding the Way to Well-being

well-being

Wellness is the map of actions and thoughts that we use to guide us toward a higher quality of life — one with more well-being moments. Our wellness map is tailored to meet our individual needs and must be flexible and adaptable. Life throws out frequent curveballs, and human resilience depends on how well we can adapt our wellness map. I have Parkinson’s, and I continually tweak the wellness map to the changing conditions of this progressive disease.

My new onset of vision loss required more than tweaks; it called for some significant changes to my wellness map. Understanding the basic structure of a wellness map is helping me to find my way to further moments of well-being.

The process of making a wellness map involves a design that meets individual needs, accesses available resources, is implemented, and is followed up. A successful wellness map will utilize the resources available to the individual, including support, strengths, and history of well-being experiences. The wellness map should be implemented with compassion and sacred intent. Finally, a follow-up will evaluate the map’s success. These processes are all intertwined into a holistic view of wellness.

Few of us are professionally trained in all of the complexities of human wellness. We need knowledge of illnesses and available treatments, and also the wisdom about the efficacy of wellness possibilities. We require wisdom from the experts to keep our wellness map functioning at the highest possible degree. The process of choosing the experts and incorporating their wisdom into our personal wellness plan is tied into the science of human decision-making.

Each of us has individual wellness needs, and we use our own decision-making processes to design and implement our wellness map. The CHRONDI Creed contains the fundamental elements for building a Parkinson’s wellness map, but it doesn’t address the process of upgrading one’s personal map in the face of new trauma.

Vision loss affects Parkinson’s in ways that I am still understanding. Vision has been a big part of how I enjoyed the beauty and science of the world. Writing, science research, photography, artwork, flower gardens, viewing the world with its multitude of colors and shapes provided me with hours of enjoyment. Loss of vision left me feeling disconnected from life. Things didn’t look as bright and beautiful as before. The pleasure that I once received from visual stimuli was not the same, resulting in a deeper understanding of how important “pleasure chemistry” and happiness are to the treatment of Parkinson’s — and the risks of losing that or trying to replace it artificially. My new wellness map will take all of this into consideration.

Some days I have no clear vision of what I need to do (no pun intended). Shifting to the basics helps — exercise, eating well, quiet mind, and gratitude. It’s a focus on healing, with little language (internal and external) about feeling sick. This doesn’t mean I should ignore my physical ailments and the treatments. It means that the sickness treatments are wrapped up in a comforting blanket of wellness. Sometimes, fatigue hits hard, and I don’t have the energy to pursue wellness mapmaking. Back to basics: rest, meditate, and let it go. I will continue tomorrow. Build patience and compassion into the wellness map.

Redesigning a wellness map is about choosing wisely how to use your time. Stay away from toxic thinking and behaviors and avoid unhealthy environments. Spend more time engaged in wellness-related thoughts and actions — those that have the greatest potential for leading to moments of well-being. Focus on being well, rather than complaining about suffering.

One carves out a little piece of time from the large amount dedicated to thinking or acting in response to sickness, and then allocates that little block of time to wellness. The wellness map is built with a practice of thought and action that bolsters the healing process and helps to hold open the door to more moments of well-being. It takes resilience, patience, and hard work to forge an improved wellness map. But it is never too late to start working on it.

What changes have you had to make to your wellness map recently?

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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.

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$6.6 Million Grant Will Fund Research Into Environmental Cues That May Trigger Parkinson’s

grant awarded

Scientist Kim Tieu, PhD has received a $6.6 million grant to investigate the environmental factors that may trigger the death of brain cells in Parkinson’s disease, and to develop therapies that prevent their loss.

The grant from the National Institute of Environmental Health Sciences (NIEHS) is part of its Revolutionizing Innovative, Visionary Environmental health Research (RIVER) program. It provides funding for eight years so that researchers can tackle challenging, but potentially revolutionary, lines of research.

Parkinson’s disease is characterized by the death of dopaminergic-neurons, a class of neurons that produce the neurotransmitter dopamine. Neurotransmitters are substances produced in response to nerve signals that act as chemical messengers and allow nerve cells to communicate.

While a small percentage (less than 10%) of all cases of Parkinson’s disease can be attributed to genetic mutations, in most cases, the cause of the disease is unknown. Environmental factors, which have been strongly associated with Parkinson’s disease, are the focus of Tieu’s research.

“We know that the environment plays a crucial role in overall health, including the brain, and that exposures to environmental toxicants, most likely in combination with an individual’s genetic makeup, may lead to all sorts of diseases, including Parkinson’s,” Tieu, a professor at Stempel College of Public Health and Social Work in Miami, Florida, said in a press release.

“Some of the environmental factors that we will study are manganese and pesticides to better understand how they promote the accumulation and spread of toxic proteins in the brain,” Tieu said.

Recently, Tieu’s team reported the involvement of dynamin related protein-1 (Drp1) in Parkinson’s disease. Drp1 functions to split mitochondria (cells’ powerhouses). Researchers found that inhibiting Drp1 improves dopamine’s release and reduces neurodegeneration in mouse models of Parkinson’s disease.

Now, researchers want to investigate the role of Drp1 in the accumulation of toxic proteins involved in Parkinson’s disease and how different types of brain cells (namely glial cells and neurons) and genetic variants may render neurons more susceptible environmental toxins.

Recent evidence suggests that bacteria in the gut (known as the gut microbiome) may trigger Parkinson’s disease, a relatively new area of research that also will be the focus of Tieu’s lab.

“New evidence suggests that the accumulation of toxic protein in Parkinson’s disease may not start from the brain itself, but rather may spread from the gut. This is something that we need to investigate further and try to stop it,” Tieu said.

By exploring different avenues that may underly the development of Parkinson’s disease, Tieu hopes new therapies may be developed.

The R35 RIVER grant is given to outstanding investigators in environmental health sciences, giving him (professor Tieu) and his lab the freedom to do research over several years with the support of NIEHS,” said Tomás R. Guilarte, dean of Stempel College.

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Cellular Respiration Compound May Ease Symptoms, Reduce Neuronal Loss, Study Finds

cellular respiration compound

Delivering a compound called nicotinamide adenine dinucleotide to the striatum, a key brain region involved in motor control, can ease Parkinson’s symptoms and reduce dopamine-producing neuronal loss in a mouse model of the disease, a study finds.

The study, “Protective effects of β-nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson’s disease,” was published in Progress in Neuropsychopharmacology & Biological Psychiatry.

Found in all living cells, nicotinamide adenine dinucleotide (NAD) is a coenzyme — or a substance that enhances the action of an enzyme — used for a series of body functions, including cellular respiration.

Although its Parkinson’s trigger remains to be identified, research indicates the causative mechanisms involve genetics, nonworking mitochondria (cells’ “powerhouses”) and oxidative stress — an imbalance between the production of free radicals and the ability of cells to detoxify them. Taken together, these molecular and cellular changes eventually cause the death of dopamine-producing neurons — the type of nerve cell that is gradually lost in Parkinson’s disease.

“In particular, it has been found that a reduced level of nicotinamide adenine dinucleotide (NAD) may cause mitochondrial dysfunction, DNA repair defects and neuronal death, resulting in many age-associated neurodegenerative pathologies,” the researchers said. That means that, in theory, restoring NAD levels could prevent the loss of dopamine-releasing neurons.

A Chinese team of researchers investigated whether an NAD injection into the striatum could alleviate Parkinson’s motor deficits and reduce dopaminergic neural loss in a rodent model of the disease.

Animals were given a NAD injection into the right striatum four hours before being injected with a neurotoxin called 6-hydroxydopamine (6-OHDA) into the same brain structure. This neurotoxin causes cellular dysfunction and the death of dopaminergic neurons. To a degree, it replicates Parkinson’s in a laboratory setting.

The rodents’ motor behavior was assessed four weeks after this procedure.

Compared to controls, NAD treatment eased Parkinson’s motor symptoms in animals injected with the 6-OHDA neurotoxin. In addition, brain tissue analysis revealed 6-OHDA-induced dopaminergic neuronal loss was significantly reversed by NAD injection. This was found both in the striatum and in the substantia nigra, another key brain region involved in motor function that is also affected in Parkinson’s.

Scientists then used cell culture technology to test if administering NAD to cells before they were damaged by 6-OHDA could protect them from cellular structural and molecular damage — including oxidative stress and mitochondrial problems.

Results revealed that the almost 50% reduction in cell viability caused by 6-OHDA was markedly reduced if cells were treated beforehand with NAD. The neurotoxin also caused changes in cell morphology (the size, shape and structure of cells), increased oxidative stress levels, and impaired mitochondrial function. Importantly, these alterations were all reversed following NAD pre-treatment.

“These results add credence to the beneficial role of NAD against parkinsonian neurodegeneration in mouse models of PD [Parkinson’s disease], provide evidence for the potential of NAD for the prevention of PD [Parkinson’s disease], and suggest that NAD prevents pathological changes in PD via decreasing mitochondrial dysfunctions,” the team concluded.

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Accordion Pill Can Ease Motor Fluctuations in People with Advanced Disease, Phase 2 Data Show

Accordion Pill trial results

Oral treatment with Accordion Pill-Carbidopa/Levodopa (AP-CD/LD) lessened the variability of levodopa plasma levels and eased motor fluctuations in people with advanced Parkinson’s, according to results of a Phase 2 trial.

The study, “Pharmacokinetics and efficacy of a novel formulation of carbidopa-levodopa (Accordion Pill®) in Parkinson’s disease” appeared in the journal Parkinsonism & Related Disorders. These findings were also presented at the recent 2019 IAPRD World Congress, in Montreal.

Progressive depletion of dopamine levels in the brain results in the hallmark motor symptoms of Parkinson’s. Levodopa is the standard treatment and normally given with carbidopa to ensure delivery to the brain and conversion to dopamine.

People with advanced disease often develop motor fluctuations, characterized by a return of symptoms between levodopa doses due to the drug’s short-term effects. This is associated with levodopa’s limited absorption in the upper part of the gastrointestinal tract.

Intec Pharma’s AP-CD/LD aims to address this problem. The pill has a specific gastric retention and release system with carbidopa and levodopa, which enables release in both immediate and controlled-release modes. Controlled release enables a slow discharge into the stomach over eight to 12 hours, and potentially more steady absorption.

The multicenter, open-label Phase 2 study tested multiple doses of AP-CD/LD – 50/250 mg, 50/375 mg and 50/500 mg — twice per day in more than 60 patients. The treatment’s pharmacokinetics (PK) — its absorption, distribution, and metabolism in the body, and its excretion — and effectiveness were compared to Sinemet, an approved immediate-release (IR) combination (marketed by Merck) which contains 37.5 mg of carbidopa and 150 mg of levodopa.

Results of groups 1 to 4 — out of the six taking part in the trial — showed that all AP-CD/LD doses led to more stable plasma levels of levodopa than Sinemet, and significantly lessened levodopa’s maximum concentration by 57.1% and 66.8% in patients with and without motor fluctuations.

The 50/375 and 50/500 doses significantly reduced motor fluctuations compared to the patients’ current treatment. These doses lowered the mean daily off time — when patients experience tremors and dyskinesia, or involuntary movements — by up to 45% compared to Sinemet.

In turn, the total duration of on time (without dyskinesia) and good on time — without dyskinesia or with non-troublesome dyskinesia — were greater with these AP-CD/LD doses than with Sinemet, as were the proportions of total or good on time during waking hours. Overall, both the duration of off periods and/or on time with troublesome dyskinesia were significantly reduced with both AP-CD/LD doses.

The findings further showed that both these AP/CD-LD doses significantly improved patient and investigator ratings on the Global Clinical Impression scale of Parkinson’s severity.

Treatment-emergent adverse events associated with AP-CD/LD use were in line with the known safety profile of CD/LD formulations. No new safety issues were found throughout the trial.

“AP technology demonstrated effective controlled-release PK performance and reduced motor response fluctuations in advanced [Parkinson’s] patients,” the scientists wrote.

“Importantly, the substantially improved ON time for the AP versus IR [Sinemet] was attained without an emergence of troublesome dyskinesia,” they added.

Intec Pharma is conducting a Phase 3 study in the U.S., Europe and Israel called ACCORDANCE (NCT02605434) that will compare the safety and efficacy of AP-CD/LD and Sinemet in 462 adults with advanced Parkinson’s. Two different AP-CD/LD doses are being tested — 50 mg of carbidopa with 400 or 500 mg of levodopa, two or three times a day.

As these doses generally match those used in the Phase 2 study, the investigators expect “similar stable LD and CD plasma levels within the therapeutic range necessary for [Parkinson’s} symptom control.” Topline results are reported as likely to be released this summer.

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MJFF Nationwide Event Series ‘Parkinson’s IQ + You’ Kicks Off This Fall

Parkinson's IQ + You

A new nationwide event series aims to empower people with Parkinson’s (PD) and their caregivers to manage the disease, learn about research participation, and plug into local resources.

Called “Parkinson’s IQ + You,” the effort is presented by The Michael J. Fox Foundation (MJFF). The events seek to support PD families in learning more about all facets of the disease — what a comprehensive care team looks like, how to achieve optimal communication between patients and physicians, the latest in treatments, and the benefits of joining clinical trials.

Kick-off events are slated this year for Atlanta on Sept. 14, and southern California, in Anaheim, on Dec. 14. More sessions will come next year, including one in Phoenix on Jan. 11. Registration is free. This year’s events will be hosted by Larry Gifford, a patient and host of the “When life gives you Parkinson’s” weekly podcast.

“Between its symptoms and progression, Parkinson’s can present unique challenges for those of us who live with the disease, but also for our loved ones who support us,” John L. Lipp, a writer, nonprofit executive director, and Parkinson’s patient, said in a news release.

“I often say, ‘I can’t control my Parkinson’s, but I can control how I respond to it.’ Parkinson’s IQ + You will offer people in the community, including me and my husband, an opportunity to learn from other patients and families and from experts in the field, so that we can turn education today into action tomorrow,” Lipp said.

Crafted to support care partners and people with Alzheimer’s at every disease stage, the series will feature a variety of panel participants, including patients and their caregivers, to reflect the community’s diversity and the disorder’s variability. The organizers note that PD symptoms and progression vary significantly, making each Parkinson’s experience unique.

Each full-day event will feature interactive programming, as well as an exposition of local resources. Called Parkinson’s Partner Expo, this portion will include representatives from movement disorder centers and patient advocacy organizations, speech and physical therapists, and clinical trial teams.

There also will be panels and sessions on topics such as understanding Parkinson’s and living well with it. During a related forum called “If I Knew Then What I Know Now,” a patient and caregiver will share experiences and strategies. There also will be a session on “Building Your Care Team.”

To help people with Parkison’s and their caregivers understand the advantages of seeing a specialist, what to expect during visits, and how to optimize each one, each event will feature a demonstration of what a typical appointment might be.

“Patients are the force driving our research priorities and our urgent mission to end Parkinson’s,” said Todd Sherer, PhD, the foundation’s CEO. “The foundation is committed to ensuring all people with Parkinson’s, and their families, are empowered to make decisions about treatment and care. And we want to work side by side in partnership with patients to advance Parkinson’s research.”

The series includes complimentary meals, and is funded by Acadia Pharmaceuticals, with additional support from MJFF biotech and pharmaceutical partners.

“The Parkinson’s IQ + You program has been uniquely designed to bring much-needed support and information to the Parkinson’s community,” said Rob Kaper, MD, Acadia’s senior vice president and global head of medical affairs.

“We look forward to this national series of events across the country, which will offer attendees the opportunity to interact with healthcare experts and other people with Parkinson’s and their families, and ask important questions about disease management,” he said.

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Pressing Through and Pushing On with Parkinson’s Disease

Parkinson's, blessings

Just when I was going to have a pity party, I received this question from a reader: “What’s your secret for dealing with the everyday?” Her question was in response to an article I wrote. Her frustration had to do with her not being able to embrace the “gift” that Parkinson’s disease seems to offer. So, my pity party was postponed and I was called to practice what I preach.

Life with Parkinson’s isn’t a gift, per se, as it seems to take away more than it gives. It’s hard to embrace a gift that seems to be taking from us all things good and replacing the good with what sometimes seems to be a curse. But “gifts,” both large and small, can be found from having a life with Parkinson’s.

For example, we obviously don’t consider it a gift when this disease takes our ability to walk with ease and forces us to watch every step we take. But did you ever consider it a gift that six friends, who you otherwise wouldn’t see regularly, make it a priority to take turns walking with you?

I call that a blessing. A gift. A breeding ground for magic to happen.

I visited a friend in the hospital. As I approached the front entry doors, I spotted my reflection in the glass. ‘They” say people with Parkinson’s can tend to resemble a drunkard when they walk. Seeing my reflection in the window, I understood why. I wanted to cry. I had every reason to, but I didn’t. Instead, I pushed through, pressed on. I walked in the entrance and took the elevator up two floors to hopefully cheer up and encourage my friend who is in worse shape than me. 

So, what is my secret to dealing with the everyday? Just that. I push through and press on. 

I see my reflection and know that I must move forward and not give up. I might not like what I see or how I feel but I must remember that’s not me in the glass. The reflection is Parkinson’s. Inside of that reflection is the me you can’t see. 

How do I push through and press on? 

I’m not joking around when I tell you to try watching cotton fluff bounce down to the ground from the trees like freshly blown bubbles offered from a child’s lips. The sunshine, serving as a backdrop behind the fluff, gives the illusion of minuscule angels dancing before me in slow motion. 

There is real magic — gifts and blessings — in those pieces of fluff. My grandson calls the fluff “summer snow” as it is released from the trees in the heat of the day. I more often than not call it a nuisance. But when I look for the magic that fluff holds inside, I can’t help but see it as summer snow as well and want to chase white magic alongside him. 

You may wonder what that has to do with pushing through and pressing on. In order to push through and press on, you must find the blessings, the gifts, the magic of this life, whether living with Parkinson’s or not. If you don’t, you will find yourself drowning in grief and despair, welcoming apathy to your very front door. And, apathy is not a good house guest.

I notice my symptoms progressing. I can’t stand the drooling and whether I like it or not, it’s increasing. My speech is also slurring more. 

It is through these progressions I must press on and push through even harder. 

I can’t let progression defeat me. So it is at times like this I look for magic. Blessings. Gifts.

When is the last time you went outside and noticed what flies, sings, smells, or floats along with the summer breezes? The last time you saw magic happen right in front of you? When did you last feel like giving in but instead pressed on and pushed through? Slam the door on the unwanted and press on and push through and you will begin to see the blessings, the gifts, and the magic in each new day.

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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.

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Participants Sought for Clinical Trial Testing ENT-01 for Parkinson’s Dementia

ENT-01

Enterin Inc has enrolled the first patient in its Phase 1b DEMET clinical trial investigating the effectiveness, safety and tolerability of small molecule ENT-01 to treat Parkinson’s disease dementia.

Contacts and locations of participating sites can be found here.

Many neurodegenerative disorders involve aggregation of misfolded (harmful) proteins in the brain. Parkinson’s is characterized by a buildup of the protein alpha-synuclein in the brain, which forms clumps known as Lewy bodies that damage and kill nerve cells.

In order to form aggregates, these clumps need to stick to the membranes that line the inside of neurons. It is the sticky form of alpha-synuclein protein that causes most of the damage seen in Parkinson’s, more so than if this protein was freely floating within a neuron.

ENT-01 (kenterin) enters neurons from the enteric nervous system (ENS), attaches itself to the nerve cells’ membrane and dislodges Parkinson’s-related alpha-synuclein clumps. By unsticking harmful alpha-synuclein, the investigational treatment reduces the amount of alpha-synuclein aggregates within neurons and, in theory, cellular death.

The enteric nervous system is a network of neurons that independently governs the function of the gastrointestinal tract. Previous studies claim that alpha-synuclein begins accumulating in the ENS and then travels from the gut to the brain, where it is linked to the development and progression of Parkinson’s.

The multicenter, randomized, double-blind DEMET study (NCT03938922) will assess ENT-01’s effectiveness, safety and tolerability in patients diagnosed with Parkinson’s disease dementia. It expects to enroll 40 participants (aged 30 to 90 years), who will be assigned randomly to receive ENT-01 or a placebo tablet. Both will be taken once a day.

By being taken orally, and because ENT-01 is not absorbed into the bloodstream, the molecule will solely act on the gut’s neurons, changing the communication between the gut and brain.

The trial will be conducted on an outpatient basis and each patient will have to visit the clinic five times. The study’s primary goal is to evaluate if the experimental therapy improves cognition in people with Parkinson’s  dementia. Investigators also will assess ENT-01’s effects on attention, social function and frequency and/or severity of hallucinations/delusions.

In two separate Phase 2 clinical trials, NCT03047629 and NCT03781791, ENT-01 has been shown to ease both motor and non-motor symptoms of Parkinson’s, indicating its potential to change disease progression.

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CYP2D6 Enzyme Could Be Therapeutic Target in Parkinson’s, Study Suggests

CYP2D6

Blocking an enzyme that converts compounds derived from certain foods and tobacco in the brain may become a therapeutic target for people with Parkinson’s, according to a new study of mice.

The research, “Mitochondria-targeted cytochrome P450 CYP2D6 is involved in monomethylamine-induced neuronal damage in mouse models,” was published in the Journal of Biological Chemistry.

Prior research has shown that a synthetic opioid known as MPTP and related compounds can induce alterations similar to Parkinson’s in rodents and primates. It is thought that an enzyme called monoamine oxidase B (MAO-B), present in the nervous system’s glial cells, oxidizes MPTP into a toxic metabolite called MPP+. This metabolite is then transferred by dopamine transporter proteins to dopamine-producing neurons, which are typically affected in people with Parkinson’s disease.

Scientists at University of Pennsylvania had already found that the CYP2D6 enzyme, present in mitochondria — the cells’ power plants — also could be involved in transforming MPTP to MPP+.

“CYP2D6 is known to play a role in influencing the activity of a number of drugs,” Narayan Avadhani, PhD, the study’s senior author, said in a press release. These include antidepressants, antihypertensive medications, opioids, selective estrogen receptor modulators, and antidiabetic therapies, among other types of treatments.

The researchers focused on toxins called beta-carbolines and isoquinolines, which resemble MPTP and are produced by the body from compounds found in tobacco smoke, alcohol, and some foods. Prior studies indicated these toxins may induce Parkinson’s-related changes in rodents, but the mechanisms remained unclear.

Using a mouse model, the results showed that CYP2D6 activates beta-carbolines and isoquinolines inside dopamine-producing nerve cells, leading to cell damage, oxidative stress (cellular damage as a consequence of high levels of oxidant molecules) and impaired mitochondrial function, as occurs in Parkinson’s disease.

Then, the team observed that mice lacking CYP2D6 did not show the same disease-related alterations and that administering CYP2D6 blockers — quinidine or ajmalicine — could prevent neuronal damage.

Experiments in a type of cells that mimic human dopaminergic neurons, called Neuro2a, revealed that cells mainly producing mitochondria-targeted CYP2D6 were more sensitive to toxin-mediated respiratory impairment than those predominantly expressing endoplasmic reticulum-targeted CYP2D6. Of note, the endoplasmic reticulum is a key cellular structure in the production, folding, modification, and transport of proteins.

Upon exposure to the toxins, nerve cells expressing mitochondrial CYP2D6 also showed production of Parkin and Drp1, protein markers of autophagy — a cellular process in the removal of aggregated and toxic proteins, as well as other components — and mitochondrial fission.

The findings also suggest that targeting CYP2D6 may be a better approach than targeting MAO-B, which has led to mixed success in previous work. “We believe that mitochondrial CYP2D6 is the more direct drug target, which might prove better in treating idiopathic Parkinson’s,” Avadhani said.

Avadhani also said that ajmalicine, found in the medicinal plant Rauwolfia serpentine long had been used in India for treating mental disorders such as paranoia and schizophrenia.

“Mitochondrial targeting of such compounds is likely to be effective in treating Parkinson’s patients, and pursuing that is our future strategy,” he said.

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The Race of My Life

Slow Is the New Fast

Participate or compete?

Prior to being diagnosed with Parkinson’s disease, I used to participate in 5K walks and duathlons for fun. Now, I am competing in the race of my life, which is fighting back against the debilitating effects and progression of Parkinson’s. Some days, I stagger and fall, and other days, I am victorious. Tomorrow is always another day.

Courage does not always roar. Sometimes, courage is the quiet voice at the end of the day saying, ‘I will try again tomorrow.’” —Mary Anne Radmacher

Completing a 5K trail run in 2007. (Photo by XTERRA Planet)

The above photo was taken in 2007, the year I battled and survived tonsil cancer. I never thought I would be able to be pain-free again, let alone complete a 5K trail run in extreme heat. In 2015, I survived the suicide of my soul mate, Steve. We had been together for over 33 years, and he helped me through my cancer battle. Now it is just me, battling Parkinson’s on my own.

“That which does not kill us makes us stronger.” —Friedrich Nietzsche

I am living proof of that.

Complacent? Not!

My mantra (which I am not always good at living up to) is “I am better than yesterday, but not as good as tomorrow.” There is no rest for the weary. Those of us with Parkinson’s cannot let our guard down or allow ourselves to become complacent. Parkinson’s is a formidable adversary, and we cannot leave any stone unturned as we strive for our quality of life. When I retired from my corporate job of 37 years, I had planned to also retire somewhat from my rigorous daily exercise routines. Unfortunately, I was diagnosed with Parkinson’s within five years of my retirement.

“The best-laid schemes o’ mice an’ men [often go awry].” —Robert Burns

What is in my arsenal?

My best weapons for battling this disease are support groups, attitude, and movement. My Rock Steady Boxing classes give me a lot of bang for the buck. I get the support and camaraderie of others who have Parkinson’s, plus I get great exercise. Trying to project a more positive attitude has also helped me tremendously. There is no question in my mind that Parkinson’s has stolen my motivation; however, I can still draw on my muscle memory and discipline to get me moving every day. I developed these qualities over the years as a dancer and cyclist.

Who is my inspiration?

I can’t even begin to imagine what it must be like for someone with Parkinson’s who has never exercised in their life to start an exercise program. Chances are, they will also suffer from fatigue, apathy, and lack of motivation, which makes the prospect of having to exercise every day that much more daunting.

These are the people who inspire me to continue on and compete in the race of my life.

“Live to inspire, and one day people will say, because of you, I didn’t give up.” —Unknown

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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.

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AV-101 Reduces Parkinson’s Dyskinesia Without Amantadine Side Effects, Preclinical Study Suggests

AV-101 results

VistaGen Therapeutics’ candidate, AV-101, reduced levodopa-induced dyskinesia (abnormal involuntary movements) while maintaining levodopa activity in a non-human primate model of Parkinson’s disease.

Importantly, AV-101 treatment did not cause the adverse side effects observed with amantadine, a therapy that works similar to AV-101 to ease Parkinson’s symptoms.

Hallmark motor symptoms of Parkinson’s disease include tremor, slowness of movement (bradykinesia), stiffness (rigidity), jerky movements (dyskinesia) and poor balance. As the disease progresses, patients typically need to gradually increase treatment dose for maximum benefit. Even after that, symptoms sometimes reappear or worsen due to the dopaminergic therapy’s gradual loss of efficiency.

Dyskinesia is one of the complications of long-term levodopa therapy that affects many patients with advancing Parkinson’s. These sudden, involuntary movements can be treated with amantadine, which acts on a specific part of NMDA receptors — molecular structures involved in neuronal communication — in the brain.

Amantadine’s exact mechanism of action is not fully understood, but studies indicate it inhibits NMDA receptors and reduces the levels of a chemical messenger called acetylcholine, which increases dopamine activity and provides anti-parkinsonian effects.

Nonetheless, the dose of amantadine needed to treat dyskinesia is often associated with side effects such as depression and cognitive impairment.

AV-101, developed by VistaGen, is an oral NMDA receptor antagonist that, unlike amantadine, acts on a different part of the receptor.

Researchers compared AV-101’s effectiveness to lower levodopa-induced dyskinesia to that of amantadine.

AV-101 was given to non-human primates that had been treated previously with MPTP, a neurotoxin that induces death of dopamine-producing neurons and mimics Parkinson’s symptoms.

AV-101 significantly reduced the abnormal, involuntary movements without affecting the timing, extent, or duration of the therapeutic benefits of levodopa.

“The antidyskinetic activity of AV-101 that we measured compares favorably with our observation with amantadine in parkinsonian monkeys,” Thérèse Di Paolo, PhD, one of the study’s authors, said in a press release.Di Paolo is on the faculty of pharmacy at Laval University in Quebec, Canada. Di Paolo is amongst the world’s leading researchers focused on Parkinson’s disease and levodopa-induced dyskinesia.

Importantly, the experimental therapy did not raise any safety concerns. “Better than amantadine, with its known side effects (in humans with Parkinson’s disease and in parkinsonian monkeys), we observed no adverse effects with AV-101,” Di Paolo said.

“We believe these preclinical data and AV-101’s positive safety profile in all clinical studies to date support AV-101’s potential to treat LID [levodopa-induced dyskinesia], while both maintaining the antiparkinsonian benefits of levodopa and without causing hallucinations or other serious side effects that may be associated with current amantadine-based therapy for LID,” noted H. Ralph Snodgrass, PhD, VistaGen’s chief scientific officer.

Scientists plan to present the preclinical results at an upcoming conference.

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