Wellness: Finding the Way to Well-being

JUNE 28, 2019 Dr. C

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?

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2019/06/28/well-being-wellness-map-resilience/

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

JUNE 28, 2019 BY CATARINA SILVA IN NEWS.

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.

https://parkinsonsnewstoday.com/2019/06/28/cellular-respiration-compound-may-ease-symptoms-reduce-neuronal-loss-study-finds/

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

JUNE 28, 2019 BY PATRICIA INACIO, PHD IN NEWS.

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.

https://parkinsonsnewstoday.com/2019/06/28/niehs-grant-study-environmental-cues-trigger-parkinsons-disease/

Fighting Parkinson’s through fitness

Published on: June 28, 2019     By STEPHEN FLANAGAN JACKSON

This physical trainer is at your beck and call; focus is on seniors and fighting Parkinson’s

EA Fitness owner Eric Allen, pictured on right, visits homes and senior living facilities. Rock Steady Boxing is a program that helps Parkinson’s disease sufferers.

By STEPHEN FLANAGAN JACKSON

An amazing number of entrepreneurs operate in the South Shore area. One of the most unique is Eric Allen, president and CEO of EA Fitness. You do not go to him. Allen comes to you! If you are out of shape physically, stressed out, want to maintain your good physical condition or need some physical rehabilitation, Allen’s mobile services as a trainer are a phone call or email away. Like Delta, he is ready when you are. And like Domino’s, he comes to your home.

Allen responded to the following questions in an exclusive interview with The Observer News:

How long have you been in business in Hillsborough County? Where are your business locations?

EA Fitness has been providing senior fitness solutions services in Hillsborough County for six years. Our business location is our client’s home or senior living facility. Our Rock Steady Boxing Class is conducted at the Sun Towers Retirement Community.

What type of business do you own?

EA Fitness is a fitness company that focuses on senior citizens. Our unique business conducts in-home functional training services, group fitness classes (Fired Up For Fitness) at senior living facilities, and Rock Steady Boxing to help people fight back against Parkinson’s disease.

What did you do professionally before your present business?

Before EA Fitness, I was a research ethics consultant.

Where did you grow up, attend high school, and attend college?

I was born and raised in Washington, D.C., and attended high school there. I finished high school in North Carolina and completed my undergraduate degree in Exercise and Sports Science at Greensboro College and earned my Master’s degree from UNC Greensboro in Liberal Studies.

What are some of the challenges of your business?

Awareness is one of the biggest challenges EA Fitness faces. Many individuals only look towards a physical/occupational therapist without the knowledge that qualified personal trainers can assist seniors, following the completion of their therapy and when they are not eligible for physical/occupational therapy.

Eric Allen, president and CEO of EA Fitness, specializes in helping seniors get or stay in shape from the comfort of their home or senior living facility. His Rock Steady Boxing program helps those suffering with Parkinson’s disease.

Connecting with local neurologists so they can advise their patients that Rock Steady Boxing is worldwide is also a challenge. We need to connect with local neurologists to inform them of our local EA Fitness program here in Sun City Center and have them partner with us to recommend people battling Parkinson’s to our class and training.

Growing the email newsletters’ following has been challenging. We have two newsletters: one for people fighting Parkinson’s disease and another for caregivers.

What gives you a sense of contentment and satisfaction with your business?

The thing that gives me the most satisfaction is knowing that I am helping my clients “Win at Life.” Our company motto is “Don’t let what you can’t do stop you from what you can do.” So finding ways to aid seniors to improve their quality of life provides me with contentment. Additionally, I am thrilled when I hear stories from my clients, indicating that they can participate in life instead of observing life because of the physical training work that we have done together.

What are the short- and long-term outlooks for the South Shore area?

The short-term goal of EA Fitness is to develop an interactive class on balance, which will teach seniors how to avoid falls, fall safely, get off the floor independently, and help them learn how their bodies are indicators for losing their balance.

The long-term goal of EA Fitness is to develop a senior fitness repository guide that will include indexed exercises and videos specifically for seniors to reference and to use to improve both their knowledge of fitness and their individual strength, quality of life, and dietary habits.

Eric Allen, president and CEO of EA Fitness, specializes in helping seniors get or stay in shape from the comfort of their home or senior living facility. His Rock Steady Boxing program helps those suffering with Parkinson’s disease.

Anything you would like to add, either about your business or your personal/family life?

EA Fitness works primarily with seniors with any physical, cognitive/neurological, or impacting physical disease(s) such as arthritis, etc., which falls in line with our company motto “Don’t let what you can’t do stop you from what you can do.” Visit our website to see what our clients have to say about working with EA Fitness. Visit eafitness.org/pages/testimonials.

The founder and CEO of EA Fitness, Eric Allen, is an avid sports fan and still plays competitive basketball.

Allen also enjoys riding his road bike all over Tampa, where it’s common for him to ride 7 to 15 miles. His passion for sports rolls over into his training in both exercises and motivational analogies.

http://www.observernews.net/2019/06/28/fighing-parkinsons-through-fitness/

First patient enrolled in Parkinson’s treatment study

June 28, 2019

A trial has begun in the US for the ENT-01 therapy treatment of Parkinson’s, with the first patient enrolled.

The first patient has been enrolled in the DEMET study to investigate novel compounds to treat Parkinson’s disease (PD). The trial is an open-label multi-centre study taking place across 15 US sites.

The study, held by CNS pharmaceutical company Enterin Inc, will enrol 30 patients over a six-month period. Patients will be administered with escalating daily doses of ENT-01, followed by a fixed dose for 25 days.

The company is progressing ENT-01 through clinical trials in an attempt to reverse the constipation and neurologic symptoms of PD.

The study will establish the safety, tolerability and efficacy of orally administered ENT-01, a synthetic derivative of squalamine, which is not absorbed into the bloodstream. The compound acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signalling from gut to brain.

Synthetic squalamine was recently shown to prevent the build-up and reduce the toxicity of alpha-synuclein, implicated in the pathogenesis and progression of PD. The compound was shown to displace alpha-synuclein aggregates from the inner wall of nerve cells and to prevent the stiffness which develops in C. Elegans worms engineered to produce alpha-synuclein in its muscles.

https://www.drugtargetreview.com/news/45709/first-patient-enrolled-in-parkinsons-treatment-study/

PhoreMost, C4X Discovery announce neurodegeneration collaboration

28th June 2019    By Anna Smith

PhoreMost and C4X Discovery have announced a neuro-degeneration focused drug discovery collaboration, aiming to initially accelerate C4X Discovery’s Parkinson’s disease drug discovery pipeline.

Under the terms of the agreement, PhoreMost’s next-generation phenotypic screening platform, Siteseeker, will be used to guide selection of novel targets identified by C4XD’s proprietary target identification platform, Taxonomy3, and provide chemical starting points to launch drug discovery programmes.

The companes announced that the aim of the collaboration is to bolster the C4XD drug discovery pipeline of novel neurodegeneration drug targets. Initially Siteseeker will enable the progression of several Parkinson’s disease targets to multi-target disease area partnering arrangements, or in-house C4XD drug discovery programmes.

“Neurodegeneration is a therapeutic area that has a pressing need for new and better targets,” explained Dr Chris Torrance, CEO of PhoreMost.

He continued, “The opportunity to incorporate genetic insights gained from C4XD’s Taxonomy3 data alongside our Siteseeker screening platform has great potential to reveal highly relevant novel drug targets. We are tremendously excited by the complementarity of our technologies.

“C4XD’s Conformetrix approach is ideally suited to use the 3D biological shape information derived from Siteseeker and convert this into small molecules starting points that will lead to the next generation of therapeutics.”

Parkinson’s disease is a progressive neurological disease with more than an estimated 10 million people worldwide living with the disease.

While the terms of the agreement are not disclosed, it is expected that both companies would share any revenues on validated targets produced by the collaboration.

http://www.pharmatimes.com/news/phoremost,_c4x_discovery_announce_neurodegeneration_collaboration_1292808

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

 JUNE 27, 2019  BY MARY CHAPMAN 

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.

https://parkinsonsnewstoday.com/2019/06/27/mjff-nationwide-event-series-parkinsons-iq-plus-you-kicks-off-this-fall/

Pressing Through and Pushing On with Parkinson’s Disease

  JUNE 26, 2019 BY "SHERRI WOODBRIDGE "

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 drunkardwhen 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 griefand 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.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2019/06/26/finding-lifes-blessings/

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

JUNE 26, 2019 BY JOSE MARQUES LOPES, PHD IN NEWS.

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.

https://parkinsonsnewstoday.com/2019/06/26/cyp2d6-enzyme-therapeutic-target-parkinsons-disease-study/