Breaking the silence on incontinence

By Sheryl Jedlinski

I recently came within seconds of living out one of my worst nightmares… becoming incontinent in public and exposing my embarrassing secret to the world. For the first time, I realized just how much shame and my fear of being discovered were negatively impacting my life, and I promised myself it would end right then.

I went online to read up on bladder issues and found that my condition is quite common, and easily treatable, if not curable. One in two women over the age of 50 and two-thirds of people with Parkinson’s disease have bladder issues, with incontinence a common, though little talked about, symptom. By discussing the topic, we rob incontinence of the hold it has on us, leading us to seek treatment and regain a better quality of life. Knowledge is power, as the saying goes.

It was only after I asked a friend directly how she was coping with her incontinence that she told me about a device she purchased online that seemed to help her almost right away. I decided to look into it and follow her progress. Motivated by competition, I’ve challenged myself to beat incontinence before my 2-1/2 year old granddaughter is potty-trained.

Incontinence can be caused by many things includingurinary tract infection, side effects of medications, weakened pelvic floor muscles, overactive bladder, obesity, and Parkinson’s. How incontinence affects daily living differs from person to person, depending on the severity of the condition, personality, and coping strategies. Left untreated, bladder issues can disrupt quality and quantity of sleep, cause problems at work, and reduce enjoyment of sex.

Never knowing when or where I may have an “accident,” has me questioning whether leaving home is worth all the stress it creates… but only momentarily.I did not live withParkinson’s for 21 years and survive two bouts of advanced stage cancer to allowincontinence to keep me from enjoying life.

This epiphany came to me when I was overcome by the urge to use the restroom in the middle of a play I was seeing with my husband, Tony, and some friends. Do I shelter in place and hope my “dam” holds or leave now and attract unwanted attention?

With way too much time remaining until the final act, I could not risk wetting myself and my upholstered seat. Prepped for this moment, I was sitting on the aisle in the very back of the theatre and had taken extra medicine to ensure I would be able to move and make a fast exit, if necessary. Tony quickly retrieved my walker from an usher and, with the help of a stranger, pulled me to my feet and up two stairs. Another usher pushed open the two sets of doors leading to the lobby. Disaster was averted.

I had no idea what a big business incontinence is until I began shopping for absorbent pads. Standing in front of the wall of pads at my local pharmacy, I was overwhelmed by the choices. How significant is the difference between “ultimate” and “maximum” absorbency? How do I know whether I need an extra long length pad? I felt like I was 13 again, looking at sanitary napkin products. This celebrated rite of passage, shared with girlfriends and whispered to relatives, has no equal when it comes to browsing adult pads. Another stigma to be vanquished.

Treatment depends on the type and cause of your bladder control problem, how serious it is, and what best fits your lifestyle. Start with the simplest and safest treatments first.

• Avoid bladder irritants including alcohol, caffeinated drinks (e.g. coffee, tea, and pop).
• Drink enough water so you won’t become dehydrated.
• Maintain a healthy weight.
• Train your bladder to increase the interval between emptying and the amount of fluid it can hold.
• Practice pelvic floor muscle (Kegels) exercises to strengthen and tone the muscles that support the pelvic organs and control the opening and closing of the bladder.

If all these approaches fail, see your doctor to discuss medical and surgical options as a last resort.

Each of us must decide for ourselves whether we give in to incontinence and become prisoners in our own homes or go forth into the world prepared with the knowledge we need to tackle whatever life may throw us at. I choose the latter; how about you?

https://livingwellwithparkinsonsdisease.com

Left-handed DNA found - and it changes brain structure

September 5, 2019   By James Gallagher

Scientists have found the first genetic instructions hardwired into human DNA that are linked to being left-handed.

The instructions also seem to be heavily involved in the structure and function of the brain - particularly the parts involved in language. 

The team at the University of Oxford say left-handed people may have better verbal skills as a result. 

But many mysteries remain regarding the connection between brain development and the dominant hand. 

What does this tell us?

About one in 10 people is left handed. 

Studies on twins have already revealed genetics - the DNA inherited from parents - has some role to play. 

However, the specifics are only now being revealed.

The research team turned to the UK Biobank - a study of about 400,000 people who had the full sequence of their genetic code, their DNA, recorded.

Just over 38,000 were left-handed.

And the scientists played a giant game of spot-the-difference to find the regions of their DNA that influenced left-handedness.

The study, published in the journal Brain, found four hotspots.

"It tells us for the first time that handedness has a genetic component," Prof Gwenaëlle Douaud, one of the researchers, told BBC News.

But how does it work?

The mutations were in instructions for the intricate "scaffolding" that organises the inside of the body's cells, called the cytoskeleton.

Similar mutations that change the cytoskeleton in snails have been shown to lead to the molluscs having an anticlockwise or "lefty" shell.

(Remember the quest to find Jeremy the garden snail a mate because, in the snail world, righties and lefties can't have sex as their genitals are in the wrong place as far as the other is concerned?)

Jeremy the "lefty" snail and one of his right-spiralling-shell offspring

Scans of participants in the UK Biobank project showed the cytoskeleton was changing the structure of the white matter in the brain. 

"For the first time in humans, we have been able to establish that these handedness-associated cytoskeletal differences are actually visible in the brain," Prof Douaud, who is herself left handed, said.

In the left-handed participants, the two halves of the brain - the left and right hemispheres - were better connected and more co-ordinated in regions involved in language.

The researchers speculate left-handed people may have better verbal skills, although they do not have the data from this study to prove it.

The study also showed slightly higher risks of schizophrenia, and slightly lower risks of Parkinson's disease, in left-handed people.

Does this change what it means to be left-handed?

Being left-handed has often led to a raw deal.

"In many cultures being left handed is seen as being unlucky or malicious and that is reflected in language," said Prof Dominic Furniss, a hand surgeon and author on the report. 

In French, "gauche" can mean "left" or "clumsy". In English, "right" also means "to be right". 

"What this study shows is that being left-handed is just a consequence of the developmental biology of the brain, it has nothing to do with luck or maliciousness," Prof Furniss said. 

"And it is driven at least in part by genetic variants we've discovered.

"This adds to the understanding of what makes us human."

Is this the end of the story?

Far from it.

The best guess is handedness is 25% genetic and 75% down to the environment (anything that's not in the genes).

Yet this study has found only the first 1% of that genetic component and only in a British population. 

So, much more work is needed to understand the genetic component of handedness in people across the globe, never mind what the huge environmental effects are, and then piece together how those elements result in people being either left or right handed. 

https://www.bbc.com/news/health-49579810

Fourth annual Parkinson's SuperWalk goes Sunday in Ste-Anne-de-Bellevue

JOHN MEAGHER, MONTREAL GAZETTE    

September 6, 2019

Parkinson SuperWalk is fundraiser as well as a great opportunity for people with Parkinson’s to meet others living with the disease, talk with their families and build a network.

Murray McBain (right), seen here participating in a boxing demo with an instructor from Otis Grant Boxing at the 2018 SuperWalk, is very active with Parkinson Canada. He is a member of the Parkinson support group and boxing class at the Cummings Centre and a participantin many Parkinson Canada events and seminars. LOUISE CHENEVERT

The fourth annual Parkinson Canada SuperWalk will take place this Sunday, Sept. 8 in Ste-Anne-de-Bellevue.

“We hope to make this year bigger and better to raise money for people living with Parkinson’s, and education and research into Parkinson’s disease,” said spokesperson Lisa Mintz.

“Last year we had 150 attendees and raised $35,000.”

Registration starts at 12 p.m.

The 1 p.m. walk begins at the Casgrain Gym building at John Abbott College. There are two routes — 1.5 km and 4.5 km — which you can stroll, walk or run. Organizers say the 1.5 km route is “completely accessible to people of all abilities.”

Live performance by the West Island musical group Pendulum Swing and members of the Lakeshore Unitarian Universalist Congregation Choir will entertain participants along the walk.

The public will also have the chance to meet Parkinson researchers and hear about their work.

If you’re interested in participating in the walk or supporting someone who will be walking, you can register at www.superwalk.ca or call Lisa Mintz 514-357-4291 or send an email to lisa.mintz@parkinson.ca

https://montrealgazette.com/news/local-news/west-island-gazette/fourth-annual-parkinsons-superwalk-goes-sunday-in-ste-anne-de-bellevue

Herndon Teen Wins National Scholarship for Method to Diagnose Parkinson’s Disease

By Fatimah Waseem    September 6, 2019 

Neeyanth Kopparapu

The Davidson Institute for Talent Development has selected a Neeyanth Kopparapu, 17, of Herndon as a 2019 Davidson Fellows Scholarship winner. 

The senior at Thomas Jefferson High School for Science and Technology is one of 20 students across the country selected for the program, which offers scholarships between $10,000 and $50,000 for developing projects that have the potential to benefit society in science, technology, engineering, mathematics, literature, and music. 

Kopparapu developed what the institute said is the first diagnosis system for early-stage Parkinson’s disease using an MRI scan. The Herndon resident was inspired to create the system — which is accurate nearly 97 percent of the time — after his grandfather was diagnosed with the disease at a late stage and was unable to use commonly-prescribed medication to fight the disease.

“I am incredibly grateful to the Davidson Institute for this recognition of my work in artificial intelligence,” said Kopparapu in a statement. “I am looking forward to meeting other Fellows and becoming part of the Davidson Fellows Scholarship community.”

Siona Prasad, 18, of Vienna, was also selected for the scholarship. Her work to measure and monitor greenhouse gas emissions successfully predicted an emission inventory for Washington, DC. A reception program to honor the fellows is set for Friday, September 27 in the District. 

“I am incredibly grateful to the Davidson Institute for this recognition of my work in artificial intelligence,” said Kopparapu, a rising senior at Thomas Jefferson High School for Science and Technology in Alexandria. “I am looking forward to meeting other Fellows and becoming part of the Davidson Fellows Scholarship community.”

https://www.restonnow.com/2019/09/06/herndon-teen-wins-national-scholarship-for-method-to-diagnose-parkinsons-disease/

UAB one of eight national Udall Centers of Excellence in Parkinson’s disease

By Bob Shepard       September 06, 2019

The University of Alabama at Birmingham is one of eight Udall Centers of Excellence in Parkinson’s Disease Research by the National Institutes of Health. The Udall Centers, begun in 1997, are funded by congressional legislation in honor of former U.S. Rep. Morris Udall of Arizona, who died in 1998 after a long battle with the disease.

The Alabama Udall Center is led by David Standaert, M.D., Ph.D., the chair of the Department of Neurologyand an international leader in Parkinson’s disease.

A major goal of the Alabama Udall Center since its inception in 2018 was the development of a clinical research core, directed by Talene Yacoubian, M.D., Ph.D., associate professor of neurology, to aid in the recruitment of clinical research subjects, in collaboration with Columbia University. The clinical core has recruited a cadre of 40 research subjects during the past year.

“UAB has a long history of important research in Parkinson’s disease and the clinical research core is an important next step in efforts to develop therapies to treat or prevent Parkinson’s,” said Standaert, the John Whitaker Endowed Chair of Neurology at UAB.

The Alabama Udall Center was established by an NIH award of nearly $10 million over five years. Standaert says the center is focusing on the role of inflammation and immune response in the progression of Parkinson’s, which is a new approach to the disease.

“Parkinson’s is a progressive disease, which means it gets worse over time,” Standaert said. “There has been a lot of research on the triggers of the disease, such as genetics and environmental causes. We have gained a good understanding of how that fire gets lit, but we don’t know how it spreads. Our efforts will concentrate on the role of inflammation in the brain as a driver of the worsening of the disease.”

Standaert says the Udall designation builds on a previous P20 grant to UAB from the NIH’s National Institute for Neurological Disorders and Stroke, which established a core collaborative team in Parkinson’s, demonstrated the university’s ability to recruit patients for clinical studies, developed and standardized models and methods, and created a process to study immunomodulation in animal models and humans with early disease.

The UAB center has three primary research efforts. Standaert leads a clinical study of 60 newly diagnosed patients with Parkinson’s and 60 healthy controls looking for signs of inflammation very early in the development of the disease.

A second arm of the Udall Center is focusing on immunology and the role of the immune system through basic research. This arm, led by Etty Benveniste, Ph.D., Charlene A. Jones Endowed Chair in Neuroimmunology and professor in the Department of Cell, Developmental and Integrative Biology, will examine a signaling pathway known as JAK/STAT as a novel therapeutic strategy for Parkinson’s. The JAK/STAT pathway delivers communications from outside of a cell to the cell nucleus.

The center’s third major research focus is on the LRRK2 kinase enzyme, which has been studied extensively in the lab of former UAB researcher Andrew West, Ph.D. West, now at Duke University, continues to work in collaboration with the Alabama Udall Center.

Laura Volpicelli-Daley, Ph.D., assistant professor of neurology, leads an animal models core in support of the second and third arms of the center’s research.

Udall Centers are very involved in community outreach and education of the next generation of Parkinson’s clinicians and researchers. The Alabama Udall Center will work with the Parkinson Association of Alabama, the American Parkinson Disease Association, and other regional and national organizations to enhance communication between scientists and the community of people affected by Parkinson’s disease. The Udall Center will also provide training to physicians and health care providers on state-of-the-art approaches to diagnosis and treatment of Parkinson’s disease.

Parkinson’s affects about 1 million people in the United States and 10 million worldwide.

“The cure for Parkinson’s disease still remains elusive; but if we can find a way to slow or stop the progression of the symptoms, we can help many people live full and active lives. We believe that the studies the Alabama Udall Center will conduct on the role of immune signaling can lead to the discovery of these desperately needed disease modifying treatments,” Standaert said.

https://www.uab.edu/news/campus/item/10743-uab-one-of-eight-national-udall-centers-of-excellence-in-parkinson-s-disease

LSVT Big presented at Parkinson’s meeting

September 6, 2019

LSVP Big

KEARNEY — The Parkinson’s meeting for this month will be 2-3 p.m. Monday at First United Methodist Church, 4500 Linden Drive. Meetings are open to anyone with movement disorders and their caregivers.

The group will host Matt Lewis, a physical therapist at New West. Following a short exercise session, he will present the LSVT Big, a program that is designed specifically for treating a person who has Parkinson’s.

The Parkinson’s Support Group will not meet in October, as the Parkinson’s Symposium in Omaha is scheduled for that day. Call Theresa Harris at 308-224-9908 with questions.

https://www.kearneyhub.com/news/local/lsvt-big-presented-at-parkinson-s-meeting/article_f4dcc97c-d0b3-11e9-8eb5-7b8ed595acc8.html

Our Idea of Fun Is Sharing Moments Together

SEPTEMBER 6, 2019 Dr. C

“Fun” is an F-word that doesn’t have a strong history in our home. My partner and I are from the “nose to the grindstone, make it happen, pursue the American dream” generation. Oh, and we try to live up to the adage “Become the change you wish to see in the world.” We can be intense.

With all those noble ideals, we find that doing fun things is very difficult. We don’t know how people take fun vacations. We have never been successful at doing that. Sure, we want to have fun times in our retirement years, but through all the chronic illness time commitments, chasing that little F-word requires more tweaks in the wellness map.

To illustrate how we can’t accomplish the standard idea of fun, I share this story about our attempts at a honeymoon. The first one — the one usually planned by newlyweds — never happened because my wallet was stolen at the wedding reception. There’s no traveling without credit cards or identification. Four years later, we tried for a second honeymoon. During an idyllic trip to Maine, my wife developed a tremendous migraine — her first — so we cut the trip short.

Twenty years into our marriage, we tried to combine a job relocation/house-hunting expedition/vacation at my new job site in Reno, Nevada, with a stay at a casino. We had the heart-shaped velvet bed and all expenses were paid by the company, but our minds were on finding a rental unit quickly and coordinating a 1,500-mile relocation with the movers. It was the last time we used other people’s definitions of fun as our own.

Forty years post-nuptials, we were more successful in combining a trip to Arizona for a friend’s wedding with exploring the countryside and downtown Phoenix. There were no demands on our time other than dealing with chronic disease symptoms.

Changing behaviors that are so deeply ingrained in our lives is what tweaking the wellness map is all about, and it is never easy. We give ourselves permission to have fun and yet, at the same time, we must balance our plans with our ability to achieve it.

Once, we could be more spontaneous or at least show up for activities that had been on the calendar for weeks. Now, we tentatively agree to be somewhere, but roll with the day when it arrives. We wake up knowing that each day must be faced as it presents itself. If we just don’t have the energy or physical ability to meet that obligation, we change the date and try to not feel guilty.

It may seem strange to give ourselves permission to have fun, but we do this every day. If we listen only to that inner worker voice, then each day is just about the quest to accomplish something. “One more thing off the list!” my wife says, with as much glee as the Queen of Hearts in “Alice in Wonderland” ordering heads to be chopped off.

But there is a new voice now. We still wake every day asking ourselves (and each other), “What are we going to accomplish today?” But we know we must be flexible. Is this going to be a good day with enough energy to do what is on the schedule? We give ourselves permission to decline or reschedule activities based on how the day unfolds.

The new normal of traveling with a chronic disease requires a separate medication bag, pillows and a cover in the back seat of the car for those off periods, a cane for days when balance and coordination are a problem, a driving schedule that allows a more leisurely pace, and a calendar that tries not to make too many commitments in a week. We try to plan one meal at a restaurant to take a break from the drive, pull over more frequently at rest areas on the interstates, or make hotel accommodations for the night to rest before tackling the next day’s commitment. More tweaking of the wellness map.

Perhaps we really do have fun. It’s just different from how other folks define it. Playtimeand time experiencing a lightness of being are both part of fun and adjusting to Parkinson’s, but so is creativity. Fun is gardening, walking our forest path, genealogy, writing, reading, organizing our mineral collection, watching a movie, and just being together to share the journey. We find our fun applying our talents to creative projects and shared moments together, and not letting chronic disease ruin the day.

How do you find fun in your life?

***

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/2019/09/06/fun-taking-time-recreation-work-scheduling-wellness-map/

Keeping Songs Going in the Head Helps Parkinson’s Patients Walk More Naturally, Study Says

SEPTEMBER 6, 2019 BY CATARINA SILVA, MSC 

Singing a rhythmic tune out loud or, even better, simply listening to it play in your head can help older adults — including those with Parkinson’s disease — to walk more naturally and at a steadier pace, a study reports.

The study, “Mental Singing Reduces Gait Variability More Than Music Listening for Healthy Older Adults and People With Parkinson Disease” was published in the Journal of Neurologic Physical Therapy.

People with Parkinson’s disease tend to walk slower and with less stability than healthy adults of similar age. Lower gait speed is thought to be a consequence of shorter step lengths and decreased step frequency, indicating a decline in overall health.

Listening to music (what scientists refer to as an external auditory cue) is known to help normalize gait speed in Parkinson’s patients. “By creating an external template to which people can align their footfalls, auditory cues impose a walking cadence that, presumably, reduces reliance on defective internal timing mechanisms and increases motivation, thereby increasing walking speed,” the researchers wrote.

External cues essentially set a pace that listeners respond to, restoring a rhythm to their gait and reducing variability.

But it doesn’t always work as intended, the researchers noted. Some studies have found that listening to music can actually increase gait variability in some Parkinson’s patients and older adults, possibly reflecting “the difficulty of synchronizing to an outside source.”

Washington University (WUSTL) researchers previously reported that singing aloud (an internal cue) leads to motor benefits in Parkinson’s patients similar to those in people who did well listening to music (an external cue).

This team now set out to determine whether singing aloud without music or singing to oneself mentally could elicit similar gait improvements as listening to music, reasoning that such an internal cue “utilizes vocal-motor coupling to match one’s movement to one’s own voice,” they wrote.

A total of 60 people, 30 men and 30 women, were included in the study. Half were diagnosed Parkinson’s patients and the other half were healthy older adults serving as controls. Patients (all tested in an “on” state of medication) had a mean age of 65.8, and controls a mean age of 64.9.

Participants walked under three distinct test conditions: listening to music, or singing aloud without music and singing mentally. All three tests were also performed at three different tempos: at the person’s preferred walking speed (cadence), 10% slower, and 10% faster.

“All conditions were cued using an instrumental version of ‘Row, Row, Row your Boat’ designed with a salient beat that could be readily detected by participants. Everyone was familiar with the lyrics and melody of the song and able to sing it without difficulty,” the researchers wrote.

As expected, Parkinson’s patients walked slower, took shorter steps, and had higher levels of gait variability and asymmetry that did healthy adults.

Both controls and patients showed a better walking performance with mental singing, with benefits similar to those triggered by external cues.  “However, only internal cues elicited improvements in gait variability as well,” the researchers wrote.

In their earlier work, these researchers showed that singing aloud generally lowered gait variability measures in ways that compared with externally generated cues. This time around, they found that singing to yourself mentally elicited even greater reductions in variability than overt singing.

Walking at a faster than the usual pace — prompted by a faster tempo — was also associated with improved velocity and lesser gait variability in both groups. “Variability decreases were more substantial during mental singing at tempos at or above preferred cadence,” the researchers wrote.

“[M]ental singing provides more benefit to gait variability than singing aloud, which makes internal cueing more practical for everyday use,” they concluded, adding that optimizing the use of internal cues to aid movement “is an important step toward more effectively meeting the needs of people with gait disorders related to aging or neurological disease.”

https://parkinsonsnewstoday.com/2019/09/06/keeping-songs-going-in-the-head-helps-parkinsons-patients-walk-more-naturally-study-says/

Parkinson’s Advocates Set to Lobby US Lawmakers for Greater Research Support, Patient Assistance

SEPTEMBER 6, 2019 BY MARY CHAPMAN 

Joined by leaders in Parkinson’s (PD) research and public policy, some 150 patients and advocates from across the nation will gather in Washington, D.C., on Monday for the 2019 Parkinson’s Policy Forum.

The annual advocacy event, taking place Sept. 9–10, is presented this year by the Parkinson’s Foundation and The Michael J. Fox Foundation for Parkinson’s Research(MJFF), with support from nine other organizations. With the aim of improving the impact of policy on PD research and care, the forum offers an opportunity for those living with Parkinson’s to not only connect, but to share their journey with elected officials.

”Policy and research must work hand-in-hand to speed scientific breakthroughs for patients and their families,” Todd Sherer, PhD, the Fox foundation’s CEO, said in a news release. “The Parkinson’s Policy Forum brings the community together to advocate for government policies that support research and care. Its goal is to improve quality of life for everyone impacted by the disease today.”

Forum attendees — mostly patients and care partners — will spend a full day with foundation and its scientific and policy experts brushing up on effective advocacy, and exploring ways to help shape their message. They’re off to Capitol Hill the next day, where advocates will apprise legislators of the ways in which policy can help — or hinder — Parkinson’s research and care. They’ll focus specifically on the economic burden of PD, as well as recent legislative moves to limit out-of-pocket prescription medicine costs for Medicare patients, and improve access to mental health services.

The nonprofit organizations said it’s vital that advocates and policymakers seize on current momentum in Parkinson’s, particularly in research and clinical drug testing. By next year, it is estimated that nearly 1 million U.S. residents will be living with the progressive disease.

”People with Parkinson’s disease and their families need legislative action with increased federal research funding to expand access to care that will help patients live healthier lives,” said John Lehr, CEO of the Parkinson’s Foundation. “The Parkinson’s Foundation leverages our nationwide network of healthcare professionals and research advocates to mobilize around PD community policy priorities. To better serve people with Parkinson’s and their families we must ensure they continue to have their voice heard by lawmakers.”

Visit this site for more forum information:  http://www.parkinsonsforum.org

https://parkinsonsnewstoday.com/2019/09/06/advocates-lobby-us-lawmakers-at-annual-parkinsons-policy-forum/

Enterin’s ENT-01 Restored Bowel Motility in Constipated Parkinson’s Patients

SEPTEMBER 4, 2019 BY ANA PENA, PHD IN NEWS.

Daily treatment with tablets of ENT-01, an investigational therapy for Parkinson’s disease, is safe and may restore patients’ bowel movements, according to results from Enterin‘s Phase 2a RASMET study.

ENT-01 seems to locally stimulate a network of nerve cells that directs bowel function, suggesting that part of the nervous system is not irreversibly damaged in Parkinson’s patients.

The trial has been completed and results are reported in the study, “Targeting neurons in the gastrointestinal tract to treat Parkinson’s disease,” published in the journal Clinical Parkinsonism & Related Disorders.

In Parkinson’s disease toxic aggregates of alpha-synuclein protein accumulate in the enteric nervous system (ENS), as they do in the brain. The ENS is a network of nerve cells that regulates the function of the gastrointestinal (GI) tract independently of the central nervous system (CNS) — the brain and spinal cord.

Several studies have noted that accumulation of alpha-synuclein in the ENS may be the reason why some Parkinson’s patients are affected by dysmotility (lack of normal bowel movements) and constipation.

To find a treatment for this medical problem, Enterin is investigating ENT-01 (or kenterin), a lab-made version of squalamine expected to act locally on enteric nerve cells, altering gut-to-brain signaling and stimulating gut motility.

Squalamine is an antimicrobial compound found in the dogfish shark, that is able to enter cells and displace certain protein-membrane aggregates, preventing the build-up of alpha-synuclein into toxic clumps.

RASMET was a Phase 2a multicenter, dose-escalating trial (NCT03047629) to evaluate the safety, tolerability and effectiveness of oral ENT-01 to relieve symptoms of constipation in people with Parkinson’s disease.

The trial, which ran over a period of nine months, enrolled 50 Parkinson’s patients who had been constipated for more than six months; they were recruited at 15 sites in the U.S.

In the first phase of the trial, 10 patients received a single escalating dose (from 25 to 200  mg a day or a maximum tolerated dose) every three to seven days, which was followed by a two-week washout period.

During the second phase of the trial, 34 patients received daily, escalating doses from 75 to a maximum of 250  mg a day to identify ENT-01’s prokinetic dose (the dose needed to stimulate bowel motility). Patients were then randomized to receive a fixed prokinetic dose of ENT-01, or a placebo, over one week, followed by a washout period of two weeks.

The results showed that 80% of the patients reached the primary efficacy goal — an increase of at least one complete spontaneous bowel movement (CSBM) per week relative to study start, or three per week during the fixed-dose period. Efficacy criteria was defined according to FDA’s guidelines for prokinetic (promotility) agents.

Researchers also observed that the higher the ENT-01 dose, the more severe was the patient’s constipation at the beginning of the study, which is in line with the idea that the more alpha-synuclein accumulates in the ENS, the greater are its consequences for bowel motility.

This means that the dose of ENT-01 required to restore nerve cell activity is proportional to alpha-synuclein’s burden.

No safety issues were reported and adverse side effects were limited mostly to the GI tract. The most common were nausea (40% and 50% in stage 1 and 2) and loose stools (40% and 44%). The only other noteworthy side effect was dizziness (18%), researchers reported.

“We demonstrate in this study that ENT-01 can restore gastrointestinal motility in patients with PD, suggesting that a major division of the nervous system and the largest sensory organ in the body (the GI tract) is not irreversibly damaged in patients with PD, despite the long-standing constipation that might suggest otherwise,” Denise Barbut, MD, said in a press release. Barbut is the study’s senior author and Enterin’s co-founder, president and chief medical officer.

“We believe that this is the first demonstration of the reversal of a neurodegenerative process in humans,” she added.

The study also indicates potential benefits of ENT-01 for parkinsonism, cognition, hallucinations, and sleep problems.

“While these results are intriguing, this was an open label trial and placebo effects cannot be excluded. These findings must undergo rigorous evaluation in future place-controlled trials,” said the study’s lead author, Robert Hauser, MD, professor and director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida in Tampa.

Enterin is currently running a larger, placebo-controlled trial, KARMET (NCT03781791), to confirm and further explore ENT-01’s effects. That trial is ongoing, but no longer recruiting participants.

https://parkinsonsnewstoday.com/2019/09/04/enterin-ent-01-restore-bowel-motility-constipated-parkinsons-patients/