Pies for Parkinson's - A Delicious Way to Help

APRIL 20, 2018 | BY CAPECOD TODAY STAFF

Table Talk pies and Parkinson Support Network of Cape Cod have joined forces in a yummy way (Courtesy photo)

From the Parkinson Support Network of Cape Cod:

The Pies for Parkinson’s program is a grassroots awareness campaign rather than a fundraiser or particular event. Across the Cape, our board members and local businesses who have sponsored this program are distributing our pie packages (please see the attached images) to local Councils on Aging, Senior Centers, Fire houses, etc. For example, Rose Digregorio, Parkinson Support Network/APDA board member and Pies for Parkinson’s program creator, will be visiting the Barnstable Newcomers Club on April 25. The packages include information about our organization, the services we provide, a schedule of free educational events for individuals with Parkinson’s and their families, as well as how to reach us should they need information and referral services. We encourage anyone who is interested in learning more about the program to contact us.

In recognition of National Parkinson’s Awareness Month (April), the Parkinson Support Network, a branch of the American Parkinson Disease Association, Massachusetts Chapter is pleased to bring Pies for Parkinson’s to the Cape for the second year. We are thankful to Table Talk Pies for supporting this April awareness campaign again this year. We have been supporting the over 2,000 people living with Parkinson’s disease on Cape Cod since 2007. In the eleven years since, PSN has collaborated with health and human service providers, professional organizations and the public to provide access to information for individuals with Parkinson’s and their families. We have offered a variety of educational and wellness programs for our ever growing community, and in joining with the American Parkinson Disease Association Massachusetts Chapter in 2015, we gained the capabilities to help even more individuals with PD.

The American Parkinson Disease Association (APDA) is the largest grassroots network dedicated to fighting Parkinson’s disease (PD) and works tirelessly to assist the more than 1 million Americans with PD live life to the fullest in the face of this chronic, neurological disorder. Founded in 1961, APDA has raised and invested more than $170 million to provide outstanding patient services and educational programs, elevate public awareness about the disease, and support research designed to unlock the mysteries of PD and ultimately put an end to this disease.

With the APDA MA, we are able to provide an Information and Referral Center helpline (800-651-8466) and a website (parkinsoncapecod.org), along with between four or five signature educational programs annually, funding for the Cape Conservatory’s Sing for Joy group, and an annual Fall Fling Social. To learn more about any of these events or programs, please visit parkinsoncapecod.org or call 800-651-8466.

If you would like to host your own Pies for Parkinson’s event to spread awareness about Parkinson’s disease, please contact the APDA MA at 800-651-8466.

https://www.capecodtoday.com/article/2018/04/20/238888-Pies-Parkinsons-Delicious-Way-Help

Do Immune Responses Promote, or Prevent, Parkinson’s Disease?

18 Apr 2018

Researchers keep turning up unexpected links between Parkinson’s disease and the immune system. At the first Advances in Alzheimer’s and Parkinson’s Therapies Focus Meeting (AAT-AD/PD), March 15–18 in Turin, Italy, Michael Schlossmacher of the Ottawa Hospital Research Institute, Canada, reported that the PD-linked gene LRRK2 helps mice fight bacterial and viral infections. Together with previous findings that animals release α-synuclein in response to infection, the data support the idea that microbial exposure could play a role in neurodegenerative disease. And if bad bacteria can hasten PD, could good bacteria delay it? A hint in this direction came from Roberto Grau of Rosario National University, Argentina, who reported that feeding probiotic bacteria to worms prevented α-synuclein accumulation and neurodegeneration. The bacteria turned on longevity genes, which may control α-synuclein folding and degradation, Grau suggested. He is about to test his idea in an upcoming PD trial.

• A PD risk gene supercharges the immune response to fight off infections.
• Beneficial bacteria slow the accumulation of α-synuclein in mutant worms.
• Together, the data suggest that immune responses may modulate PD risk.

If confirmed, the studies imply that microorganisms, and the immune response to them, may modify PD risk, for good or ill. “We think that environmental triggers such as microorganisms interact with the genetic makeup of the host organism to initiate inflammatory responses, and those responses determine the outcome of the illness,” Schlossmacher told Alzforum. His team recently drew attention to this complex disease model of PD pathogenesis and is testing this idea in animal and human studies (Schlossmacher et al., 2017). 

The idea that systemic infections might be at the root of some cases of PD has been gaining some ground in the last decade (July 2011 news series). Researchers recently reported that gut infections stimulate the release and aggregation of α-synuclein (Oct 2016 news; Jul 2017 news). The protein is expressed in the peripheral and central nervous system neurons, as well as in red blood cells and platelets (Barbour et al., 2008; Scherzer et al., 2008). In mice, the normal gut microbiome accelerates α-synuclein pathology, while in people, the composition of gut microflora changes early in the disease (Dec 2016 news; Apr 2017 news). 

B. Subtilis Squelch Synuclein. 

PD model worms (left) accumulate α-synuclein deposits (green), but not when fed probiotic bacteria (right).  [Courtesy of Roberto Grau.]

Why does the body pump out α-synuclein in response to an infection? Last year, Schlossmacher and colleagues reported that the protein helped mice survive a virulent immune challenge, with α-synuclein knockouts succumbing sooner to a deadly virus (May 2017 news). Others have similar findings (Beatman et al., 2015). In Turin, Schlossmacher added new data, proposing a comparable immune modulatory role for LRRK2. This large multifunctional protein is highly expressed in microglia, monocytes, and adaptive immune cells, in addition to its expression in neurons and glia.

To plumb its role in infection, the researchers infected newborn LRRK2 knockout mice with reovirus T3D (Gauvin et al., 2013), and adult knockouts with salmonella bacteria. In both paradigms, the knockouts had evidence of more disease than wild-type, amassing about double the viral or bacterial burden. Female mice lacking LRRK2 were more susceptible to infection than males. Intriguingly, the pathological outcomes of female LRRK2 heterozygotes mirrored those of male knockouts, while male heterozygotes were more likely to be unaffected, responding to infection like wild-type mice. This work is currently in revision (Shutinoski B, Hakimi M, et al.).

PD-linked LRRK2 risk alleles are not knockouts, however. They are mostly gain-of-function variants that increase the protein’s kinase activity. What do those do in response to infection? Schlossmacher and colleagues tested mice that expressed the main PD risk variant, G2019S. In contrast to knockouts, they dealt with infections handily, keeping their viral or bacterial load low. Female mice survived bacterial sepsis better than males but succumbed sooner to a viral brain infection, though the number of mice examined thus far was small. 

The G2019S variant is known to boost myeloid cell recruitment, and a different LRRK2 variant is a known risk factor for an excessive inflammatory response in people with leprosy caused by Mycobacterium leprae (Fava et al., 2016). Schlossmacher speculated that G2019S may augment inflammation, which helps the body fight off a virulent infection but could possibly harm the brain. If so, G2019S’s efficacy against infections may explain why this variant has survived in humans during evolution.

If independently confirmed, LRRK2 would be the first PD gene shown to have a strong gender effect in animal studies. The reason why is unclear, but the sex difference mirrors findings in people. In the Ashkenazi Jewish population, women carrying a G2019S variant are more likely than male carriers to develop PD, and their symptoms appear five years earlier on average (Cilia et al., 2014; Marder et al., 2015). This flips the normal gender effect in PD, where men are typically more susceptible.

In future work, Schlossmacher is investigating whether his LRRK2 findings relate to PD. He believes the protein may influence how the body mobilizes α-synuclein in response to an infection. “We think LRRK2 is the horse, and α-synuclein the buggy; where the buggy goes depends on which way the horse pulls,” he told Alzforum. This raises a question for ongoing trials of α-synuclein antibodies, Schlossmacher noted. If the protein helps defend the body against infection, lowering it too much could leave people more vulnerable. “Trialists should monitor patients for signs of infection,” he suggested.

Neuron Protection? 

In PD model worms fed the standard diet of E. coli (left), dopaminergic neurons (green) degenerate; neurons stay healthy when the worms eat probiotics (right).  [Courtesy of Roberto Grau.]

Working in Rosario, Grau focused on good bacteria instead of bad. He previously reported that the probiotic Bacillus subtilis delayed aging in the roundworm C. elegansby reducing insulin signaling (Donato et al., 2017). Because aging is a risk factor for PD, he wondered if the probiotic could protect against it. He used two worm models, one that overexpressed human α-synuclein, and another that expressed a risk variant in the parkin gene. These worms develop several phenotypes mimicking PD, including clumsy movement, constipation, and impairment in dopamine-dependent behaviors such as reproduction and avoiding danger.

When the mutant worms were raised on media containing Bacillus subtilis, however, nearly all these behaviors reverted to wild-type levels. The probiotic suppressed accumulation of α-synuclein into Lewy bodies by 75 percent, and prevented the degeneration of dopaminergic neurons (see images above). The worms lived as long as wild-types. The data suggest that probiotics could possibly prevent the development of PD pathology, Grau said.

The protective effect of Bacillus subtilis depended on its ability to form a biofilm, a slimy sheet of cells surrounded by an extracellular matrix. When the researchers used a mutant strain without that ability, few benefits accrued to the worms. Bacillus lives as a biofilm in the gut, and this organization allows the cells to communicate more efficiently among themselves and with the host, Grau explained.

In his previous study, he found that Bacillus biofilms dialed down insulin-signaling genes such as DAF-2 in the host. This suppression leads to the induction of protective genes, including FOXO and heat shock factor 1. HSF1 in turn mediates the response to cellular stress, and Grau believes it may turn on molecular chaperones that assist in the degradation of α-synuclein.

Grau plans to treat PD patients with the Bacillus subtilis strain DG101, along with their normal medications, to see if the probiotic might improve health, lower symptoms, or extend lifespan. This strain robustly induces FOXO and HSF-1, he noted. The trial is expected to start later this year. He plans to enroll more than 100 people in Argentina who are being treated for PD at private hospitals and follow them for six to 12 months.

In the Alzheimer’s field, treatments that target the aggregation of pathogenic proteins have not worked in symptomatic populations, possibly due to the long prodrome of the disease. This has fueled a push toward preventative trials.

Natto, Anyone? 

This Japanese breakfast food 

fermented soybeans is made 

with B. subtilis.

 [Courtesy of Wikimedia.]

Some people around the world already consume B. subtilis. For example, a Japanese breakfast food called natto is made by fermenting soybeans using the probiotic. The Japanese credit consumption of this food as one reason for their longevity. Grau told Alzforum that natto helped inspire his studies of B. subtilis’ health benefits.

The strain that makes natto produces the protease nattokinase, which degrades amyloid in mice and promotes non-amyloidogenic processing of Aβ (Hsu et al., 2009; Fadl et al., 2013). It is unclear if the food affects PD or Alzheimer’s risk. The incidence of Parkinson’s disease in Japan is somewhat lower than in most Western countries (Muangpaisan et al., 2009).

Schlossmacher called Grau’s work elegant, with fascinating implications. He noted that probiotics might trigger shifts in the relative abundance of other species in the gut microbiome, leading to changes throughout the intestine. In theory, such microbiome changes could also help prevent PD by keeping the α-synuclein response to infection in check, he said. Signs of ongoing α-synuclein aggregation occur in healthy people in the GI tract, notably in the appendix (Gray et al., 2013), and chronic constipation is associated with PD risk. Gut motility, which is influenced in part by the GI tract’s microbiome constituents, could thus be a modifiable risk factor, Schlossmacher argues.—Madolyn Bowman Rogers

https://www.alzforum.org/news/conference-coverage/do-immune-responses-promote-or-prevent-parkinsons-disease

Never Steady, Never Still review – tough sledding in the snows of Alberta

April 20, 2018

This drama about a mother who has Parkinson’s and her teenage son who is struggling with his sexuality, is unsatisfying despite heartfelt moments

 Conflicted … Jamie (Théodore Pellerin), who plays Shirley Henderson’s son in Never Steady, Never Still.

This is a sincerely intended drama from Canadian writer-director Kathleen Hepburn, and it was a prizewinner on its home turf, but I have to admit to finding it tough sledding. It is plaintive and subdued, with a dual narrative focus that is not as satisfyingly developed or resolved as it might be.

Judy, played by Shirley Henderson, lives near the oilfields of Alberta and has Parkinson’s. She has a supportive if withdrawn husband, Ed (Nicholas Campbell), though she seems also to have an emotional connection with her neighbour Lenny (Lorne Cardinal). Judy is worried and protective about her aimless teen son Jamie (Théodore Pellerin) who, quite aside from worrying about his mother, has his own issues with sexuality and identity, and who occupies half the film’s narrative space. (The feature was developed from an earlier short that was more centred on Jamie.) In the end, I got the feeling I hadn’t quite found out enough about either Jamie or Judy.

https://youtu.be/LP-Kfh6S4c4

The movie comes most alive in Judy’s Parkinson’s therapy group scenes, which have a wit and punch that the rest of the film lacks. There is a terrific exchange in which an older woman fiercely tells the group how annoyed she was when out shopping for socks for her husband, when her wobbly legs would suddenly fail to move at her bidding and she would be stuck making conversation with the town bore. 

There are some heartfelt moments, but this is an opaque and frustrating experience.

Since you’re here …

… we have a small favour to ask. More people are reading the Guardian than ever but advertising revenues across the media are falling fast. And unlike many news organisations, we haven’t put up a paywall – we want to keep our journalism as open as we can. So you can see why we need to ask for your help. The Guardian’s independent, investigative journalism takes a lot of time, money and hard work to produce. But we do it because we believe our perspective matters – because it might well be your perspective, too.

I appreciate there not being a paywall: it is more democratic for the media to be available for all and not a commodity to be purchased by a few. I’m happy to make a contribution so others with less means still have access to information.

Thomasine, Sweden

https://www.theguardian.com/film/2018/apr/20/never-steady-never-still-review-parkinsons-shirley-henderson

Keep Your Dental Health In Check. Here’re 5 Tips

April 14, 2018

The four primary Parkinson’s symptoms – rigidity, tremors, bradykinesia, and postural instability make it hard to maintain daily oral hygiene regimen. When combined with medication fluctuations, the simple task of brushing or flossing turns into a nightmare. A hygienist, Parkinson’s fighter will understand this nightmare, which can be compounded if he/she also has missing teeth or toothaches. Not being able to chew food properly can also lead to an increased risk of choking and dangerous lung infections.

Luckily, regular visits to the dentist, proper daily brushing and flossing technique can help you eliminate most dental problems. Wondering how? Read below.

1. Use Parkinson’s friendly products 

Tremor and reduced hand-to-mouth mobility in Parkinson’s can make thorough dental hygiene very challenging. This is why it is important to use:

• A toothpaste containing fluoride. If you are not sure about the level of fluoride in your toothpaste, ask your dentist for the recommendation.
• An electric toothbrush (battery-operated with large handles) as the extra weight can help reduce tremor in your hand or arm. Interdental brushes with handles may be helpful if you have spacing in between teeth. Some may even find it easier to use a 3-sided toothbrush or one with an angled head.
• A fluoride mouthwash at a different time to brushing. Rinsing with a fluoride mouthwash will help prevent cavities. Using an over the counter rinse can also help dry mouth increase saliva.
• A flossing device with a large handle for a more comfortable grip and hold. Use Water Flosser one minute a day, prior to brushing to remove debris in between the teeth.

2. Develop a cleaning strategy 

Establish a fixed dental routine to ensure that all tooth surfaces are cleaned twice a day.  If it is hard to clean all teeth in one go, concentrate on one half of your mouth in the morning and the other half in the afternoon. Clean systematically from one side to the other and from front to back. Pay special attention to cleaning the area where the tooth leaves the gum.  You may find it easier to stand behind while brushing your teeth.

If it is difficult to hold even an electric toothbrush, slip the brush into a velcro sleeve you strap to your hand. Inserting the brush handle in a tennis ball or bicycle handlebar grip can give you something larger and less slippery to grip. As a general rule, change your toothbrush or head of the brush every 3 months.

3. Look after your denture 

If you have dentures, their proper cleaning and maintenance can make a huge difference to your dental health. Loose dentures that rub parts of the mouth can cause blisters or ulcers. In addition to this, plaque can build up on them and cause irritation to the skin on the roof of your mouth, cheeks, and gums. To look after your dentures:

• Always clean them over a sink full of water.
• Soak them overnight in water and then brush gently under water.
• Use special denture paste to clean them.
• Avoid leaving them in the solution for too long. Ensure that the solution is not too hot, as heat can damage the denture plastic.

4. Watch what you eat 

Reduce the amount of sugary food and drinks. A dietician should be able to prescribe a healthy, well-balanced diet that minimizes the risk of harming your teeth and gums. Drink water throughout the day to wash away food and drinks.

It is also important to be mindful of the number of meals you eat during the day. If you eat a number of smaller meals or snacks, greater care should be taken to keep your mouth clean. However, it is not necessary to brush your teeth every time as too much rubbing is a risk. Instead, rinse with mouthwash.

5. Visit your dentist regularly 

It is important to ensure that any dental problems are dealt at their early stages. Regular visits to a dentist will help you identify problems quickly and prevent them from getting worse. Your dentist or hygienist may:

• Show you some aids to help you clean between your teeth.
• Advise you on toothbrush handle adaptations which can help improve your grip.
• Remove persistent stains for better hygiene.
• Check poorly designed, old and worn dentures.
• Recommend you to have more frequent check-ups to keep your gums and teeth healthy.

As a general rule, you should consider visiting your dentist every 6 months.

https://9zest.com/blog/keep-dental-health-check-herere-5-tips/?utm_source=newsletter&utm_medium=email&utm_campaign=PD_E34

Michael J. Fox Recovering From Spinal Surgery ''Unrelated'' to Parkinson's Disease

 by MCKENNA AIELLO   Apr. 20, 2018

Michael J. Fox recently underwent spinal surgery, a rep for the actor announced Friday. 

The procedure was "unrelated" to his Parkinson's disease, his spokesperson Leslie Sloane confirmed to E! News. "He is recovering, feeling great, and looking forward to getting back on the golf course this summer." 

Fox recently cancelled an appearance scheduled for the last week of April at the Calgary Comic and Entertainment Expo in Canada. At the time, the event cited "unforeseen circumstances" for the reason behind his absence. 

The 56-year-old actor made an appearance on Good Morning America earlier this month, where he opened up about his role on Designated Survivor and the recent work of the Michael J. Fox Foundation.

He shared the advice he gives to people also suffering from Parkinson's Disease, saying, "That's the key. I always drive the point home: We are the answer we're looking for. We have the answers within us somewhere. We need to find a way to identify the disease before symptoms ever exist. People say 'Is there a cure?' There's not a cure, we have a lot of questions to answer before then, but we're answering them."Fox was diagnosed with Parkinson's at the age of 29, but did not go public with his health struggle until eight years later in 1998. 

Wishing Michael the speediest of recoveries! 

http://www.eonline.com/news/928957/michael-j-fox-recovering-from-spinal

-surgery-unrelated-to-parkinson-s-disease

Exercise helps with Parkinson’s

C.J. MARSHALL / PUBLISHED: APRIL 18, 2018

Although research is still being conducted on the subject, strong evidence indicates that an effective treatment for Parkinson’s Disease is intensive exercise.

April is Parkinson’s Awareness Month, and the Dietrich Theater held a presentation on Saturday (April 7), outlining the benefits of exercise for those suffering from the disease.

The event was hosted by Kathy Reap, owner and trainer of Rock Steady Boxing of Northeast Pa., and George Stonier of Tunkhannock, a certified coach in Rock Steady Boxing. Also participating at the event was Kristina Dorkoski, a physical therapist at Allied Services Integrated Health System, as well as an instructor at Misericordia University; and Maureen Pascal, an associate professor at Misericordia.

Many symptoms

Stonier, who suffers from Parkinson’s, explained that most people associate tremors with the disease. He gave a demonstration to the audience, showing how badly his hands shook during the presentation.

But tremors are only one symptom of the disease, he explained.

Parkinson’s is a chronic neurological disorder with no cure. Current treatments include medication and deep brain simulation surgery, which Stonier has undergone.

Other problems include anxiety, bladder issues, mood swings, muscle spasms, depression, difficulty sleeping, slowness of movement, stiffness of limbs and trunk, and difficulty with posture, balance and coordination.

Stonier explained that he began exercising, which at first helped offset the symptoms. But as his body became accustomed to the routine, the benefits stopped.

Rock Steady Boxing

Then in 2016, Stonier heard about a program called Rock Steady Boxing which helps people suffering from Parkinson’s through an intense physical training program.

Reap explained that she set up a Rock Steady Boxing franchise in Old Forge six years ago to help her husband, who is also a victim’s of Parkinson’s Disease. The program was developed in 2006 by Scott Newman, an attorney with Parkinson’s. Among his clients were boxers, Reap explained, and Newman trained with some of them as part of an exercise regime.

Newman discovered that he felt much better - ‘rock steady’ - from the training, and developed the Rock Steady Boxing system. Starting out as one club in Indianapolis, the franchise now has 550 affiliates across the nation.

Reap emphasized that Rock Steady Boxing does not involve fighting an opponent. It is the intense physical training which helps to offset the symptoms of Parkinson’s. Boxers train to improve hand-eye coordination, which helps reduce tremors, she explained. The training emphasizes optimum balance, which helps with posture instability. Workouts also develop improved mental focus, which offsets cognitive issues.

Reap also explained that several levels of training available, to help people start from the beginning up through the advanced stages.

Stonier said he has been training at Rock Steady Boxing in Old Forge for the past 15 months. Eight months ago, he became a certified coach.

The Old Forge facility has about 40 participants, and Stonier provides coaching to some of them.

“Having Parkinson’s, I have an advantage, because I know what they’re going through,” he explained.

While people have inquired about the possibility of starting his own Rock Steady Boxing franchise in Tunkhannock, Stonier explained he could not due to the stress and responsibility. However, if someone else wishes to start a local franchise, he would be more than willing to function as a coach at the facility.

More confirmation

Dorkoski confirmed that there is strong evidence that intense physical exercise helps offset the symptoms of Parkinson’s, and a person can obtain the same benefits from other activities. She explained that Parkinson’s patients, used as test subjects, were instructed to train on bicycles, and the results recorded. The subjects then trained on tandem bikes, with a professional cyclist in the lead. The test pushed the people with Parkinson’s to their limits, but the results showed dramatic improvement compared to when they rode on their own.

Pascal explained that Misericordia University is currently conducting a study, in which information Parkinson’s subjects are being recorded. She said that although results are preliminary at this point, evidence indicates that intense physical activity helps to offset and in some instances reverse the affects of the disease - helping people to move and feel better.

Patience is the key

Although she did not speak during the presentation, Karen Stonier - George’s wife - explained afterward what is involved in being the spouse of someone afflicted with Parkinson’s Disease.

The keyword is patience.

“There are many times when it is best to let him alone and let him do things for himself,” she said. “I don’t offer to help unless he asks for it.”

Relatives - such as his parents, her parents and their son must also be patient with George in his everyday activities, Karen explained.

“It’s tough. It takes a lot of time,” she said.

The best thing to do in such circumstances is to be sympathetic to a person with Parkinson’s, without taking away the ability to do it for themselves.

We welcome user discussion on our site, under the following guidelines:

To comment you must first create a profile and sign-in with a verified DISQUS account or social network ID

http://wcexaminer.com/news/exercise-helps-with-parkinson-s-1.2326864

Phase 2 Study of Potential Oral Therapy for Parkinson’s Dementia, Anavex 2-73,

Planned APRIL 20, 2018   BY JOSE MARQUES LOPES, PHD 

Anavex Life Sciences is planning to open a Phase 2 clinical trial testing Anavex 2-73, a potential oral treatment for patients with Parkinson’s disease dementia (PDD), this year.

Anavex 2-73 aims to treat PDD by binding to the sigma-1 receptor, located in a cellular structure called the endoplasmic reticulum and important to protein production and transport.

The proposed double-blind, placebo-controlled trial will evaluate Anavex 2-73’s ability to ease both cognitive and motor difficulties in Parkinson’s patients. A trial application is before European regulators, with plans to start this study in the second half of 2018.

According to the Parkinson’s Foundation, around 50 to 80 percent of Parkinson’s patients will develop disease-related dementia. Parkinson’s is characterized by the loss of neurons in a crucial brain area that controls movement, the substantia nigra. This loss, in turn, lowers brain levels of dopamine, a key player in nerve cell or neuronal communication.

With disease progression, these changes spread to other areas of a patient’s brain, affecting memory, attention, and thinking and reasoning.

“As many as 80 percent of people with Parkinson’s will experience Parkinson’s disease dementia and treatment options are limited,” Christopher Missling, president and CEO at Anavex, said in a press release.

Results of preclinical work, fully funded by the The Michael J. Fox Foundation for Parkinson’s Research, show that treatment with Anavex 2-73 was able to restore function to damaged nerve cells in mouse models of Parkinson’s disease. Data also demonstrated that it targets misfolded proteins and poorly working mitochondria — a cell’s energy source — to prevent oxidative stress, inflammation, and cellular stress.

“We are excited to progress our program to Phase 2, with a focus on the many patients with Parkinson’s disease dementia, and we remain focused on the discovery and development of potential treatments for neurological diseases with unmet needs, including Alzheimer’s disease and Rett syndrome,” Missling added.

Anavex filed an updated investigational new drug application to the U.S. Food and Drug Administration (FDA) earlier this year for a double-blind, Phase 2 study evaluating Anavex 2-73 in Rett syndrome. If approved, this trial is also expected to open in late 2018.

The company plans to open a Phase 2/3 trial of Anavex 2-73 in up to 300 people with mild-to-moderate forms of Alzheimer’s disease.  A Phase 2a dose-escalating study (NCT02244541) involving 32 people with probable Alzheimer’s was conducted at sites across Australia.

https://parkinsonsnewstoday.com/2018/04/20/anavex-planning-phase-2-trial-of-potential-parkinsons-dementia-oral-therapy/

Neurodegenerative Disease Mechanisms May Begin Soon After Birth,

Mouse Study Suggests APRIL 20, 2018 BY PATRICIA INACIO, PHD 

The mechanisms that lead to progressive degenerative diseases like Parkinson’s in adulthood begin much earlier than previously thought, a mouse study suggests.

In fact, they may start soon after birth, researchers said.

The study, “Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1,” was published in the Journal of Clinical Investigation.

A movement disorder called spinocerebellar ataxia type 1 (SCA1) is caused by mutations of the ATXN1 gene. It starts with coordination and balance problems and progresses over time. Symptoms typically begin in early adulthood but can appear any time between childhood and late adulthood.

Northwestern University researchers wondered when the disease’s mechanisms begin appearing. For their study they genetically engineered a mouse to mirror the human disease.

A key thing they discovered was that altered circuitry in the cerebellum — an area of the brain responsible for movement control — sets the stage for later susceptibility to the disease.

The mice lacked the ATXN1 gene. Although their disease’s symptoms appeared relatively late, their brain starting showing alterations in gene activity as early as a week 
after birth.

“Given the importance of this postnatal period for cerebellar development, we asked whether this region might be developmentally altered by mutant 
ATXN1,” the researchers wrote.

They focused on stem cells in cerebellar white matter that play key roles in the animals’ first weeks of life. The stem cells differentiate into important nerve cells — basket cells and stellate cells.

Importantly, the stem cells also give rise to cerebellar astrocytes, star-shaped cells that regulate the connections between nerve cell signaling and central nervous system blood vessels.

ATXN1 gene mutations increase the proliferation of cerebellar stem cells and influence their fate, researchers said. They way they do this is by promoting the stem cells’  differentiation into nerve cells and away from an astrocyte lineage.

“We were amazed to find that they multiplied excessively and tended to differentiate into inhibitory neurons called basket cells,” Puneet Opal, MD, PhD, a professor at Northwestern University Feinberg School of Medicine, said in a press release.

“We knew that cerebellar stem cells generate inhibitory neurons [one class of nerve cell], but in this case the number of inhibitory neurons was so much more than normal that they generated an enhanced inhibitory effect on Purkinje neurons, the chief output neurons of the cerebellum,” said Opal, who was the study’s lead author.

The changes disrupt the normal cerebellar function, he said. “This network dysfunction could be a constant stress, and that constant stress makes the neural network deteriorate over time,” he added.

While the mechanisms underlying the detrimental effects of mutant ATXN1 remain unknown, the findings point to an underappreciated phenomenon: The mechanisms of neurodegenerative diseases begin very early in life, before symptoms appear.

“This is the first discovery of alterations in an adult-onset spinocerebellar disorder that stem from such early developmental processes,” Opal said. “This may well be generalizable to a whole host of other diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and amyotrophic lateral sclerosis.”

https://parkinsonsnewstoday.com/2018/04/20/parkinson-related-study-finds-disease-mechanisms-may-begin-shortly-after-birth/