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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MS Medicine Copaxone May Have Benefits in Parkinson’s Disease, Mouse Study Finds

Copaxone

Treatment with Copaxone (glatiramer acetate), an FDA-approved medicine for multiple sclerosis, can restore motor function and biochemical markers in a mouse model of Parkinson’s disease, according to a recent study.

The findings, “Glatiramer Acetate Reverses Motor Dysfunction and the Decrease in 9 Tyrosine Hydroxylase Levels in a Mouse Model of Parkinson’s Disease,” were published in Neuroscience.

Parkinson’s disease, the second-most prevalent neurodegenerative disease of the elderly (after Alzheimer’s disease), is characterized by the gradual loss of muscle control, sometimes accompanied by cognitive deficits. It is mainly caused by the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for controlling body movements.

Unfortunately, so far, there are no treatments that effectively reduce or reverse degeneration of dopaminergic neurons associated with Parkinson’s disease.

“Glatiramer acetate (GA, also known as Copaxone), which is currently an FDA approved drug used in the treatment for multiple sclerosis, has been shown to directly dampen the pro-inflammatory response within the brain, in both mouse models of multiple sclerosis/experimental autoimmune encephalomyelitis and Huntington’s disease,” the researchers wrote.

Scientists set out to examine the therapeutic potential of Copaxone, an immunomodulatory drug, in the treatment of Parkinson’s disease.

In doing so, researchers used a mouse model of induced-Parkinson’s disease, in which the disorder was triggered by treating animals with MPTP, a neurotoxin that induces brain inflammation, loss of dopaminergic neurons, and motor impairments, as seen in patients with the disorder.

Treatment with Copaxone after the onset of the disease reversed gait (walking) and grip impairments in MPTP-treated mice.

Investigators believe this was due to the remarkable recovery in the levels of tyrosine hydroxylase (TH), one of the enzymes that is responsible for the production of dopamine in the striatum (a region of the brain involved in motor coordination) following treatment with Copaxone.

In addition, researchers found the number of TH-positive neurons in the substantia nigra increased slightly, albeit non-significantly, in animals treated with Copaxone, compared to those treated with a vehicle solution (control) after MPTP induction.

This was also associated with an increase in the levels of brain-derived neurotrophic factor (BDNF) — a protein whose main function is to protect dopaminergic neurons — and a decrease in the levels of IBA1, a marker of glial cells’ over-activation caused by brain inflammation. Glial cells, also known as microglia, are nerve cells that support and protect neurons.

Moreover, the levels of non-phosphorylated alpha-synuclein (syn-1), a protein directly involved in Parkinson’s disease, in the midbrain and striatum dropped significantly after MPTP induction and gradually recovered to normal levels after treatment with Copaxone. The midbrain is the region that connects the spinal cord to the brain, and plays key roles in motor movement  and auditory and visual processing.

“In this study, we show that GA [Copaxone] treatment results in restoration of motor impairments and recovery of the nigrostriatal pathway, (…) while dampening the microglia response and restoring BDNF levels,” the researchers wrote.

“Of note, this study also tested GA after the full regimen of MPTP had been completed, a time point at which there is no further loss of TH within the striatum or substantia nigra, showing that GA is a potential neurorestorative agent that has significant translational value for patients with PD [Parkinson’s disease]. To our knowledge, we are the first to test GA in a true restoration animal model of PD, resulting in recovery of the nigrostriatal pathway, leading the way for repurposing of this FDA approved drug,” they added.

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Overcoming the Grief Caused by Parkinson’s

Journeying Through Parkinson's

One thing that many people might not associate with experiencing Parkinson’s disease is grief. Experiencing grief with this disease is real. It can be felt deep down in your soul, whether you are the one who actually has the disease or you are the caregiver. You mourn for a life that used to be, and fear it may never be again.

Although our life changes in unexpected ways and fear threatens to consume our days and terrorize our nights, we can learn to overcome those wretched feelings. Innumerable people miss out on the rich experiences and blessings they have been given today because they can’t stop worrying about their future with Parkinson’s.

In “Living Beyond Your Feelings: Controlling Emotions So They Don’t Control You,” author Joyce Meyer writes, “The three most harmful negative emotions are anger, guilt, and fear.” When we have Parkinson’s disease, we are particularly susceptible to anger and fear. 

We experience anger, as evidenced when we ask ourselves the age-old question, “Why me?”

We pump our fists in the air and ask, “What did I ever do to deserve this?!” Our dreams of a better tomorrow feel as if they have been sucked dry and replaced with feelings that frighten us and worries we can’t seem to get under control. 

We think about what used to be: The days when we were able to work at a job we loved; the times when we could get down and play with our grandchildren; the summer vacations we took that used to reenergize us instead of wearing us out. Grief steps in and leaves us feeling fearful and despairing.

Two weeks ago, I lost someone dear to me. She was like a second mother to me. I babysat her daughter as a newborn. She was my maid of honor at my wedding. And when I think of her, a great sadness overcomes me: grief. It not only came upon me at the news of her passing, but also returns each time I think of her.

Getting a diagnosis of Parkinson’s disease can be like losing a loved one.

There is the initial grief, but waves of grief can still overcome us, sometimes when we least expect them. Often, those waves of grief are accompanied by fear. Not only are we dealing with what we’ve lost, but also we are fearful of what we may still lose.

Getting through grief over the loss of a loved one takes time, and the amount of time varies with each individual. It’s the same with the grief of having Parkinson’s. 

Grief is normal.

Grief is a part of life. While we must learn to accept it, it is still OK to cry. It is OK to mourn what we have lost. In that mourning, however, we need to remember that life goes on. While we may not know what tomorrow will bring, we know we have this moment right here, right now, and Parkinson’s can’t take that away.

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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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Brain Serotonin Changes May Be Early Warning Sign of Parkinson’s, Study Suggests

serotonin early warning

Changes to the serotonin system in the brain occur years before the development of motor symptoms in Parkinson’s — and may be an important early warning signal for the disease, a study suggests.

“Therefore, brain imaging of the serotonin system could become a valuable tool to detect individuals at risk for Parkinson’s disease, monitor their progression and help with the development of new treatments,” Heather Wilson, research associate at King’s College London and the study’s first author, said in a press release.

The study, “Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study,” was published in The Lancet Neurology.

Parkinson’s is characterized by the progressive death of brain cells that are responsible for producing dopamine, which eventually leads to the development of motor symptoms associated with the disease, including involuntary tremors or muscle contraction.

Studies have suggested that, in addition to changes in the dopaminergic system, Parkinson’s progression and symptoms may be associated with impaired signals from another important neurotransmitter, called serotonin. Serotonin transmits messages between nerve cells, and is thought to be active in constricting smooth muscles.

To further explore the role of serotonin in Parkinson’s progression, a team led by researchers from King’s College evaluated non-symptomatic carriers of an alpha-synuclein (SNCA) gene variant. That variant is an extremely rare mutation, but a well-known cause for hereditary Parkinson’s disease.

Individuals with mutations in the alpha-synuclein gene are almost certain to develop Parkinson’s during their lifetime, which makes them invaluable candidates to study the biological events that result in the development of the disease.

The study recruited 14 individuals who were carriers of the A53T variant in the SNCA gene, as well as 25 patients with idiopathic (of unknown cause) Parkinson’s disease, and 25 healthy matched volunteers who had no history of neurological or psychiatric disorders.

All participants were evaluated by positron emission tomography (PET) scans. PET scans use a specific dye that binds to the serotonin transporter, and evaluates serotonin metabolism in the brain. Participants also underwent several clinical assessments to determine motor and non-motor symptoms. They were evaluated for cognitive status, dopamine metabolism, and brain structural changes.

Among individuals who were SNCA mutation carriers, 50% were still asymptomatic —  at the premotor stage of the disease — and had dopaminergic deficits.

Compared with healthy controls, the premotor SNCA carriers showed reduced serotonin signals in several brain areas. SNCA carriers who still had normal dopamine transporters already showed “an average of 34% loss of serotonin transporters in raphe nuclei and 22% loss in the striatum compared with healthy controls,” the researchers said.

As the name indicates, a serotonin transporter is a protein that binds to and transports serotonin to different areas of the brain. Raphe nuclei are a type of brain receptor that decrease the release of serotonin. The striatum is a critical brain region involved in voluntary movement.

“Parkinson’s disease has traditionally been thought of as occurring due to damage in the dopamine system, but we show that changes to the serotonin system come first, occurring many years before patients begin to show symptoms,” said Marios Politis, MD, PhD, professor at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and senior author of the study.

Those who were SNCA carriers but had already been diagnosed with Parkinson’s disease showed more extensive deficits in the serotonin system, affecting even more areas of the brain. There was 48% serotonin transporter loss in the raphe nuclei, and 57%  loss in the striatum areas.

Further analysis revealed that low serotonin signals in the brainstem were associated with increased total scores on the Movement Disorder Score-Unified Parkinson’s Disease Rating Scale (MDS-UPSRS) — indicating higher disease burden. This occurred in all SNCA carriers, and in those with idiopathic Parkinson’s.

“Our findings provide evidence that molecular imaging of serotonin transporters could be used to visualize premotor pathology of Parkinson’s disease in vivo [in the body],” the researchers said.

Future studies should focus on implementing serotonin transporter imaging as “an adjunctive tool for screening and monitoring progression” for those at risk for, or who already have Parkinson’s.

“This is one of the first studies to suggest that changes in serotonin signaling may be an early consequence of Parkinson’s,” said Beckie Port, PhD, research manager at Parkinson’s UK. “Picking up on the condition earlier and being able to monitor its progression would aid the discovery of new and better treatments that could slow the loss of brain cells in Parkinson’s.”

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Wellness Journey: Finding My Way on the Map

PD Dr. C's Journey, loss of vision

How do I know when I’m getting well?

There’s that child’s voice yelling from the back seat of the car reminding me that time waits for no man. I would like to say: “Hey, we are almost there?” But I am not sure what “there” looks like.

Perhaps getting well is just “feeling like your old self again.” Saying that as a way of describing a wellness process doesn’t clearly describe the phenomena occurring during the process of getting well. What it does communicate is the idea that getting well is something people experience. People do return to an experience of “my old self” again.

The recent physical issue with my eyes, along with Parkinson’s disease, has forced me into a different perspective. I can’t give the answer I’d like to the child’s earworm, “Are we there yet?” I can answer: “The GPS has us right on track.”

Wellness map

We each have our own definition of wellness. We know that sense of feeling “like my old self.” It’s a map showing us a way from our current state to one where we feel better. There are signposts on the map that point us toward wellness. How we have come to understand these signs is likely to be as varied as Parkinson’s. It is easy in life to become so overwhelmed that it seems as if there are no signposts, and sometimes, no map. I flail about for a while, get all emotional. With help from family and friends, I return to my old self, a shift toward wellness.

I constantly remind myself that there is an atlas. To believe anything else means to disbelieve in the holistic scientific philosophy that is the foundation of my alter ego, “Dr. C.” It’s a fight to push rational thoughts over emotion in order to regulate the emotional effects following an injury or setback. It is hard to do, but the wellness map is worth the effort. Regulation of emotion is part of my wellness map.

Commonalities

I have heard, “If you have met a person with Parkinson’s, then you have met one person with Parkinson’s.” Parkinson’s expresses itself uniquely in each of our lives. In the same way, our map of wellness — or way of living well with Parkinson’s — is specific to our own way of experiencing the world. Even though Parkinson’s is slightly different for everyone, there are some shared phenomena. For example, motor control problems, change in cognitive performance, and experiencing “off-and-on” periods are just a few commonalities. It’s the shared phenomenon that helps to provide a common language for communication about not only Parkinson’s but also about our journey using the map of wellness.

Time to heal

One of the first things I do when a serious injury happens to me — and I feel upset and/or confused — is simplify life. I need time to heal. I need to make time in life to simplify the demands on my time to free up my schedule for wellness. It must be a conscious decision to put more time into wellness and to do so with a committed resilience and a sacred intent. I agree to do what I know I need to do for myself in order to heal. I am not talking about some selfish dive into a quart of Ben & Jerry’s without offering to buy a pint for your partner.

Healing while taking care of others is not only possible, it is compatible. The sense of personal sacred healing space is a space without distraction. It is focused on a state of being which best supports the healing needs at that interconnected moment. Getting back to that space after getting smacked in the face is my current journey. This is where practice has helped me. It is part of my wellness map.

I have written about the CHRONDI Creed and the compassionate warrior’s mental frame. My map includes such a mental framework. Ideally, it is not angry. Rather, it is filled with energy that can be directed as needed as a warrior in terms of preparations, resilience, and sacred intent. The idea of a sacred intent connected to our personal wellness journey is not as strange as it might seem.

In my postdoctoral thesis, I explored how for millennia we humans held great reverence for those who could facilitate the well-being of the tribe members. Sacred is not the same as religious. It is more about a reverence for the process. I have reverence for the beauty of science and for the spiritual aspects of who we are as humans. For me, there is so much intertwining to find a peaceful coexistence between the mystic side and the scientific side.

In writing about wellness, I can’t let go of one side in favor of the other. It is going to be a challenge to blend the two into a new view.

What is on your wellness map? Share your ideas in the comments.

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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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Accordion Pill May Help Reduce Motor Fluctuations in Parkinson’s Disease, Phase 2 Trial Shows

Accordian Pill, Parkinson's

The Accordion Pill Carbidopa/Levodopa (AP-CD/LD) administered three times a day reduced the variability of blood plasma levels of levodopa in Parkinson’s disease patients, which suggests that the treatment may help to ease motor fluctuations, a Phase 2 trial shows.

Warren Olanow, MD, professor at Mount Sinai School of Medicine, New York, and the study’s lead author shared these results in a scientific poster, titled “Pharmacokinetics of multiple doses of Accordion Pill Carbidopa/Levodopa in patients with Parkinson’s disease,” at the 2019 IAPRD World Congress, June 16–19 in Montreal, Canada.

Levodopa is the most widely used treatment for Parkinson’s motor symptoms, and is almost always given in combination with carbidopa — a molecule that ensures levodopa is safely delivered to the brain, where it is processed to generate dopamine. Low levels of dopamine in Parkinson’s patients lead to the characteristic motor impairments associated with the disease.

However, patients with advanced disease who are being treated with levodopa often develop motor fluctuations, which result from “off” periods (when symptoms return) between levodopa doses due to its short-term effects.

This limited effectiveness is associated with the restricted absorption of levodopa in the upper part of the gastrointestinal tract, meaning that it has a short period of absorption.

Intec Pharma’s AP-CD/LD was designed to address this problem. The pill has a specific gastric retention and release system containing carbidopa and levodopa which allows the therapy to be released in both immediate and controlled-release modes.

Controlled release enables a slow discharge of the therapy in the stomach over eight to 12 hours, potentially allowing for more steady absorption in the upper gastrointestinal tract, where levodopa is absorbed.

The Phase 2 study (NCT03576638) evaluated the pharmacokinetic (PK) profile (a compound’s processing inside the body) of AP-CD/LD compared to Sinemet (an approved combination of immediate-release carbidopa-levodopa, marketed by Merck) in 12 Parkinson’s patients.

Participants received either an AP-CD/LD capsule — containing 50 mg of carbidopa with 500 mg of levodopa — three times a day, or they were given an immediate-release Sinemet tablet — consisting of 37.5 mg of carbidopa and 150 mg of levodopa — five times a day.

Blood samples were collected pre-dose, and then at 30-minute intervals post-dose over 16 hours and again at 24 hours post-dose.

The study’s main objective was to assess the variability in the blood concentration of levopoda between four and 16 hours after dosing.

The results showed that patients treated with AP-CD/LD three times a day had less variability in the concentration of levopoda in their blood compared with those given Sinemet given five times a day. Treatment with AP-CD/LD was found to be safe as there were no reports of adverse events.

As decreasing the fluctuations in blood levopoda levels is linked with reduced motor complications, “these preliminary results suggest that treatment with AP-CD/LD may reduce motor complications compared with standard [immediate-release]-CD/LD treatment in advanced [Parkinson’s disease] patients,” the researchers wrote.

“These PK results are important as they confirm our expectations that AP-CD/LD 50/500 [three times per day] reduces levodopa variability in [Parkinson’s disease] patients, which we expect will translate to a reduction in motor fluctuations in these patients,” Jeffrey A. Meckler, vice chairman and CEO of Intec Pharma said in a press release.

Intec Pharma is also conducting a Phase 3 trial, named ACCORDANCE (NCT02605434), to compare the safety and efficacy of AP-CD/LD and Sinemet in hundreds of adults with advanced Parkinson’s.

“We are eagerly awaiting the top-line results from our Phase 3 ACCORDANCE trial in the July/August time frame and these positive PK data support our belief that AP-CD/LD treatment could provide Parkinson’s disease patients with a better baseline [levodopa] therapy to reduce motor complications,” Meckler added.

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