FDA approves drug for excessive drooling

4th July 2018      Selina McKee

Merz Neuroscience’s Xeomin has become the first agent to be approved by the US Food and Drug Administration to treat excessive drooling.

Sialorrheam, or excessive drooling, is a common symptom among patients who suffer from neurological disorders including Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral palsy (CP) or who have experienced a stroke.

The condition can occur from difficulty retaining saliva inside the mouth, issues with swallowing and from problems controlling facial muscles.

Xeomin is a neurotoxin approved for sialorrheam on the back of Phase III data showing a significant reduction in unstimulated salivary flow rate versus placebo.

The treatment also fared well on tolerability, with the overall frequency of adverse events similar between placebo and treatment groups with no new or unexpected adverse events reported, the firm noted.

"This approval represents a significant milestone in addressing the unmet needs for more than 600,000 adults who suffer from chronic sialorrhea, and underscores our commitment to improving the lives of those living with movement disorders,” noted Kevin O'Brien, vice president and US Head of Neurosciences, Merz North America.

This is the fourth neurological indication for Xeomin, which is already on the market for increased muscle stiffness in the arm of adults with upper limb spasticity, the abnormal head position and neck pain that happens with cervical dystonia in adults, and to treat abnormal spasm of the eyelids (blepharospasm) in adults who have had prior treatment with Botox (botulinum toxin A).

http://www.pharmatimes.com/news/fda_approves_drug_for_excessive_drooling_1243134

Parkinson’s sufferers find some relief with the power of dance

6 July 2018      by Tia Relji

Dance therapy is allowing patients with Parkinson’s to cope with the progressive nature of the disease, study finds

Left to right: Cassie Camilleri, Sara Houston, Natalie Muschamp, Marie-Louise Coleiro Preca

https://youtu.be/uijYYYP_JLc

Dance therapy has allowed patients with Parkinson's disease to cope better despite the progressive nature of the disease, according to lecturer and researcher Sara Houston.

Houston, who is a principal lecturer at Roehampton University involved in groundbreaking five-year research into dance for Parkinson's, was speaking during a screening of a mini-documentary on the topic.

"With dance therapy, Parkinson's patients reported feeling better despite the disease progressing... they cope better and prove more able than those who do not dance. This means they are more independent and can support themselves better."

The mini-documentary was a collaboration between voluntary organisation Step up for Parkinson's, THINK magazine and the University of Malta.

The event was opened by President Marie-Louise Coleiro Preca, Step Up For Parkinson's founder Natalie Muschamp, and THINK Magazine co-editor Cassie Camilleri.

Dance groups had a number of positive effects on patients, Houston said, as it would help them make friends and rebuild confidence.

In her research, Houston also found that as a result of the group dance therapy sessions, further groups arose, and patients were doing activities which otherwise they would not have.

Houston shared an anecdote of a patient who reported feeling "degraded" by the disease, and felt that she needed to know that her body was doing something "pretty".

"Dancing is beyond physical exercise. It helps patients feel good about themselves," Houston said.

Dance therapy for Parkinson’s is an innovative initiative which ought to be celebrated, as it provides empowerment and hope for anyone living with the disease, which is approximately 2,800 people in Malta, Coleiro Preca said during the event. Of these, 1,400 persons are diagnosed with the disease while another 1,400 are their carers.

The President expressed her support for Step up for Parkinson’s, which she said helps to educate people on the condition and strengthens resilience in favor of human dignity.

The documentary itself provided a glimpse into the lives and struggles of patients and their carers, their experience with the disease, and how dance therapy has helped to improve their lives.

Apart from the physical improvements reported by the patients, the dance classes also provide a sense of community and allows patients to make friends who are going through similar experiences. “Everyone’s in the same boat here… we are like a big family,” one couple interviewed in the documentary said.

“Even if you’re worried about something, at least you get to forget about your troubles for an hour and a half here…” another participant said.

https://www.maltatoday.com.mt/lifestyle/health/88046/watch_parkinsons_sufferers_find_some_relief_with_the_power_of_dance#.W0Ejni3MwQ4

Enzo Cilenti: how a bike bonds me to my father, a Parkinson's sufferer

Rob Kemp  July 7, 2018

Actor Enzo Cilenti, 43, who plays Yezzan zo Qaggaz in Game of Thrones is in a reflective mood. “One of my earliest memories is of being taken to the Whitaker & Mapplebeck cycle shop in our home town of Bradford to pick up my mum’s birthday gift to my dad, a new bike,”

“I was about four at the time and I remember the shop as an Aladdin’s cave of wheels, frames and parts, the smell of oil and gleaming new bikes. From that moment I was completely hooked and have cycled when I can ever since.”

Almost forty years later Enzo and his father Pietro, who has Parkinson’s, are taking part in the Deloitte Ride Across Britain to raise awareness of the disease, taking to their trusty tandem for the nine-day cycle trek from Land’s End to John O’Groats.

“We’ve done several tandem rides in aid of research into Parkinson’s disease,” explains Pietro, 66. “We rode a 100km around London at night and also Mount Ventoux (the legendary Tour de France stage climb) on the tandem - but this one will be very special. It’s always been a dream of mine to ride through this great country and it’ll probably be the last time we get to do something like this.”

Enzo and Pietro during the London night ride

For Enzo, who is married to Resident Evil actress Sienna Guillory, cycling has always played a major role in his relationship with his father and they rediscovered cycling together when Enzo’s mum bought them both places on a cycling Tour of the Alps.

“That was in 2001, before my diagnosis,” says Pietro. “Cycling through those amazing mountains on 30km long climbs was a real eye-opener. We really got to know one another well. You’d end each day with a lovely meal and sense of achievement.”

“There’s that distinctly male thing about not opening up with your peers or with your family in this case,” says Enzo. “But when you put two blokes side by side, as opposed to looking at each other across a dinner table, and suddenly stuff comes out. It’s a moment of communion, you’re breathing in a particular way because of the demands of the ride and whilst I don’t what to get too Zen about it - it’s a wonderful thing for any human to be doing to share such experiences with one of the most important people in your life.”

Enzo with his wife, the actress Sienna Guillory

Riding on a tandem however, especially on the challenge of Mount Ventoux, does test a relationship as Pietro reveals; “It can put much more pressure on both, especially if one of you feels the other isn’t doing the right thing. I used to ride a tandem with my wife – there’s a saying that any marriage that can survive the stress and pressure of riding a tandem is destined to last!”  

When the pair took to the two-seater for the Nightrider around the capital they found the experience altogether very different; “Mount Ventoux was the hardest ride I’ve done to date,” says Enzo. “But the night ride was an amazing ride for us both. I’ve lived in London for over twenty years but saw the place in a very different light that night. Just a couple of miles into it we were cycling through Piccadilly with all these boy racers in Lamborghinis looking at us two idiots on a tandem, but it was a brilliant event.”

The pair also rode the BOXCAM event from Bristol, through Oxford to Cambridge for the charity and as Pietro’s condition becomes more challenging he’s thankful for the efforts being made by them.

“We’ve got some hard days coming up but Parkinson’s UK are working hard to help us. It’s so frustrating when you see things moving in the wrong direction, in terms of the condition, but they are looking to find treatments that bring hope and relief in the short term as well as a cure in the future.”

When you put two blokes side by side, as opposed to looking at each other across a dinner table, suddenly stuff comes out.Enzo Cilenti

Enzo knows that the task – riding their 50kg tandem for nine days in a row, averaging 100 miles a day - will be tough, but he’s keen to reassure his father that they’re going to give it their best shot. “The offer to do this ride came at a perfect time. I was looking to get into better shape because a role I’d got required me to be naked. I figured that if I was going to inflict that upon possibly several million viewers I’d better get fit! Over the winter I got on an indoor bike trainer every day and I get out now several times a week slowly ramping up the mileage.”

“This disease is absolutely horrible, but it’s great that something both dad and I have a passion for can bring him some relief too,” says Enzo. “So often something half decent comes out of adversity and these rides with dad have been wonderful for both of us.”

The Deloitte Ride Across Britain takes place from the 8-16th September: www.rideacrossbritain.com. 

There is a full list of spaces available via Parkinson’s UK at www.parkinsons.org.uk/cycling

To support Enzo & Pietro visit uk.virginmoneygiving.com/Team/PeterandEnzoCilentiTeamTandem

https://www.telegraph.co.uk/health-fitness/body/enzo-cilenti-bike-bonds-father-parkinsons-sufferer/

How does Parkinson’s disease develop?

July 7, 2018

Study raises doubts on a previous theory of Parkinson’s disease…

The exact causes of Parkinson’s disease are still unknown, in a recent study a team of researchers led by Professor Henning Stahlberg from the Biozentrum of the University of Basel has now questioned the previous understanding of this disease.

The arms and legs tremble incessantly, the muscles become weaker and the movements slower − these are typical symptoms that many Parkinson’s patients suffer from. More than six million people are affected worldwide. In these patients, the dopamine-producing nerve cells in the brain slowly die off. The resulting lack of this neurotransmitter impairs motor function and often also affects the cognitive abilities.

Questionable: protein fibrils cause Parkinson’s disease

So far, it was assumed that the protein alpha-synuclein is one of the trigger factors. This protein can clump together and form small needles, so-called fibrils, which accumulate and deposit as Lewy bodies in the nerve cells. These toxic fibrils damage the affected brain cells. A team of scientists led by Prof Henning Stahlberg, in collaboration with researchers from Hoffmann-La Roche Ltd. and the ETH Zurich, have now artificially generated an alpha-synuclein fibril in the test tube. They have been able to visualize for the first time its three-dimensional structure with atomic resolution. “Contrary to our expectations, the results seem to raise more questions than they can hope to answer,” says Prof Stahlberg.

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It is important to know that in some congenital forms of Parkinson’s disease, affected persons carry genetic defects in the alpha-synuclein gene. These mutations, it is suspected, eventually cause the protein to fold incorrectly, thus forming dangerous fibrils. “However, our 3D structure reveals that a mutated alpha-synuclein protein should not be able to form these type of fibrils,” says Prof Stahlberg. “Because of their location, most of these mutations would rather hinder the formation of the fibril structure that we have found.” In brief, if the fibril structure causes Parkinson’s disease, the genetic defect would have to protect against the disease. But this is not the case. So, it could be possible that a different type of fibril or another form of the protein triggers the disease in these patients.

More investigations are now needed to understand this fibril structure. What are the effects of the alpha-synuclein mutations? Do they lead to distinct forms of protein aggregates? What is the role of the fibrils for the nerve cells, and why do these cells die? To date, the exact physiological function of alpha-synuclein is still not known. Since only the symptoms of this neurodegenerative disease can be alleviated with the current medications, new concepts are urgently needed.

The study has been published in eLife.

https://www.drugtargetreview.com/news/33125/how-does-parkinsons-disease-develop/

Earlier Parkinson’s Onset and Dystonia Symptoms Seen in GCH1 Mutations in Study

JULY 5, 2018    BY JOSE MARQUES LOPES, PHD 

Earlier disease onset and involuntary foot muscle contractions may be a consequence of mutations in the GCH1 gene in both Parkinson’s patients and those with dopa-responsive dystonia (DRD), a study reports.

These mutations may also explain the lack of problems found with the autonomic nervous system — which controls organs not under conscious control, such as the heart, stomach, and intestines — and stable cognitive health of this patient population.

The study, “GCH1 mutations in dopa-responsive dystonia and Parkinson’s disease,” published in the Journal of Neurology.

DRD is a form of dystonia, or abnormal muscle tone, that typically responds well to sustained use of levodopa, a Parkinson’s treatment. This dystonia usually manifests itself in childhood and is most commonly caused by mutations in the GCH1 gene.

Familial Parkinson’s disease, found in about 15% of all cases — is usually linked to mutations in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene.

GCH1 provides instructions to make an enzyme called GTP cyclohydrolase. This enzyme is involved in the production of certain molecules that — a low or deficient levels — limit the synthesis of the neurotransmitter dopamine.

Loss of dopamine-producing neurons in a brain area called the substantia nigra and low levels of this neurotransmitter are hallmarks of Parkinson’s disease

Studies have shown a link between DRD and Parkinson’s: symptoms of DRD and parkinsonism overlap, and more than one-third of DRD patients have a family history of Parkinson’s disease.

Mutations in the GCH1 gene are also a Parkinson’s risk factor, and may be implicated in the mechanisms common to both diseases. This could explain the link between the two.

Researchers screened 294 patients — 268 with Parkinson’s and 26 with DRD — for GCH1 mutations and to determine if such mutations resulted in different clinical symptoms from those common to Parkinson’s and dopa-responsive dystonia patients.

Besides genetic analysis, the study involved brain magnetic resonance imaging scans, assessments of dopamine transporter (DAT) in the striatum — a brain area critical in the control of movement — and metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans, used to determine problems in the autonomic nervous system of patients with Parkinson’s-related disorders.

Fifteen patients, 14 of them women, had heterozygous mutations in the GCH1 gene —  or mutations in only one of the two gene copies. Five were Parkinson’s patients, and 10 had DRD. (We carry two copies of every gene in our body, one inherited from the mother the other one from the father.)

These mutations occurred in probands — the first patient in a family diagnosed with a genetic disease — from seven families and in five sporadic, or non-familial, cases.

The prevalence of GCH1 mutations in probands was higher in DRD patients (26.9%) than in Parkinson’s patients (1.9%). In this population, DRD symptoms were also evident at an earlier age (16.5 years old) than Parkinson’s were (35.4 years old).  But DRD has a known tendency to manifest at even earlier ages, while Parkinson’s symptoms typically become evident at later ages than was seen here.

Dystonia was a common symptom, with four of the five Parkinson’s patients and seven of the 10 with DRD having foot dystonia. But rates of tremor, rigidity, gait disturbance and sleep issues were different in the two groups.

Dysautonomia — problems with the workings of the autonomic nervous system — psychosis, and cognitive decline were uncommon in both groups, Parkinson’s and DRD patients. However, these complications are frequent in patients with mutations in a different gene, the PRKN gene, and linked to the inherited juvenile form of Parkinson’s disease (occurring in those younger than 50 years of age).

“To our knowledge, there are no reports about dysautonomia in patients with GCH1mutations,” the researchers wrote. “Therefore, the low prevalence of dysautonomia seems to be a key factor for distinguishing patients with GCH1 mutations from those with the common type of [Parkinson’s].”

All patients had an excellent response to levodopa. “The prognoses of juvenile and young-onset PD and DRD are remarkably good because of the excellent response to levodopa. Therefore, we emphasize the importance of initiating genetic screening and low-dose levodopa treatment at an early stage,” they added.

All of the DRD patients and three of  the five with Parkinson’s had  normal heart-to-mediastinum ratio, which reflects sympathetic activity in the heart and is used to evaluate people with heart failure.

Five of the six DRD patent and three of four with Parkinson’s also had normal dopamine transporter levels. This contrasts with previous studies, reporting that dopamine transporter density is unusually low in Parkinson’s patents. The researchers attributed this discrepancy to possible compensatory activity in patients with GCH1 mutations.

“GCH1 mutations induce the distinctive symptoms among young or middle age at onset PD and DRD. Our findings warrant further studies for clarifying the differences between PD and DRD with or without GCH1 mutations,” they concluded.

https://parkinsonsnewstoday.com/2018/07/05/gch1-mutations-linked-with-early-parkinsons-onset-and-dystonia-symptoms-in-study/

Speak Out & Loud Crowd Program Helps Patients With Parkinson's

By:  Alexus Arthur     July 6, 2018

According to the Parkinson's Voice Project, nine out of ten people with Parkinson's are at risk of developing a weak voice that can make it hard to hear or understand them.

A program known as Speak Out and Loud Crowd helps these individuals be heard.

The Minot State Communications Disorders program received a grant and will be implementing this program for staff and students.

The Speak Out program works with patients individually and teaches them how to speak with intent and deliberation.

The Loud Crowd program focuses on maintaining those skills.

"To do this and to be able come in and have the students learn but also the patients learn is a win-win plus two," said Lisa Roteliuk, MSU Assistant Professor - Communication Disorders.

Roteliuk says that Speak Out will start this fall and Loud Crowd will follow in the spring semester for graduate students.

https://www.myndnow.com/news/minot-news/speak-out-loud-crowd-program-helps-patients-with-parkinson-s/1286748660

Michael J. Fox Foundation Grants $7.7M for New Parkinson’s Research

July 6, 2018    BY STACY GRIEVE, PHD

New research projects focused on better ways to monitor and treat Parkinson’s disease were awarded funding recently by the Michael J. Fox Foundation (MJFF).

From more than 200 funding proposals submitted to its 2018 spring funding program, 39 projects were funded. Selected projects primarily come from the United States (19), but funding also was granted to projects in 11 other countries.

The $7.7M in total funding includes programs that address the concerns of both patients and physicians: better treatments and better quality of life.

Two of the programs, Target Advancement and Therapeutic Pipeline, hope to uncover biological processes involved in Parkinson’s disease to develop new treatments.

The Improved Biomarkers and Clinical Outcome Measures Program and the Mitochondrial Biomarkers Program focus on studies that develop methods to predict disease onset and monitor its progression.

Led by Stella Sarraf, PhD, researchers at Amydis hope to develop a non-invasive eye-scanthat can be used to measure alpha-synuclein — a protein implicated in Parkinson’s development — in retinal tissue. This tool would allow for more widespread screening, earlier diagnosis and better disease-tracking.

Caryl E. Sortwell, PhD, from Michigan State University, will test how a drug normally used to treat asthma or other breathing disorders can decrease alpha-synuclein production. Because studies have shown that individuals taking an asthma drug had lower risk of Parkinson’s disease, the effect of clenbuterol (marketed as Dilaterol, Spiropent, Ventipulmin) will be tested in a Parkinson’s preclinical model.

Two other projects, from Fundacion Ciencia and Vida, Chile, and University of Georgia, will investigate if certain immune cells used for cancer immunotherapy, called CAR T-cells and natural killer cells, can target alpha-synuclein and protect brain cells in Parkinson’s disease.

German researchers will investigate if impaired daily living activities can be a predictor of Parkinson’s dementia, while Dutch scientists will assess an at-home speech therapy program using a mobile app and video conferencing with a therapist.

Samuel M. Goldman, MD, from the University of California, San Francisco will look at how exposure to certain pesticides increases the risk of Parkinson’s disease. Specifically, the team will look at how these environmental poisons affect mitochondrial DNA (a molecule whose impairment is observed in all forms of Parkinson’s disease).

“Our latest funding round builds on The Michael J. Fox Foundation’s longstanding tradition of supporting novel research poised for scientific breakthroughs that move the field toward patients’ greatest unmet need — therapies to prevent, slow or stop Parkinson’s progression — and better lives for those living with the disease today,” CEO Todd Sherer, PhD, said in a MJFF press release.

https://parkinsonsnewstoday.com/2018/07/06/michael-j-fox-foundation-grants-7-7m-new-parkinsons-research/

Study raises doubts on a previous theory of Parkinson's disease

 July 6, 2018, University of Basel

Cross section of an alpha-synuclein fibril. Left: 3D reconstruction of the fibril, showing two interacting protein molecules. Right: atomic model of the fibril structure. Credit: Universität Basel

Parkinson's disease was first described by a British doctor more than 200 years ago. The exact causes of this neurodegenerative disease are still unknown. In a study recently published in eLife, a team of researchers led by Prof. Henning Stahlberg from the Biozentrum of the University of Basel has now questioned the previous understanding of this disease.

The arms and legs tremble, the muscles become weaker and the movements slower − these are typical symptoms that many Parkinson's patients suffer. More than 6 million people are affected worldwide. In these patients, the dopamine-producing nerve cells in the brain slowly die off. The resulting lack of this neurotransmitter impairs motor function and often also affects the cognitive abilities.

Questionable: Protein fibrils cause Parkinson's disease

It has been assumed that the protein alpha-synuclein is one of the trigger factors. This protein can clump together and form small needles, so-called fibrils, which accumulate and deposit as Lewy bodies in the nerve cells. These toxic fibrils damage the affected brain cells. A team of scientists led by Prof. Henning Stahlberg from the Biozentrum of the University of Basel, in collaboration with researchers from Hoffmann-La Roche Ltd. and the ETH Zurich, have now artificially generated an alpha-synuclein fibril in the test tube. 

They have been able to visualize for the first time its three-dimensional structure with atomic resolution. "Contrary to our expectations, the results seem to raise more questions than they can hope to answer," says Stahlberg.

It is important to know that in some congenital forms of Parkinson's disease, affected persons carry genetic defects in the alpha-synuclein gene. These mutations, it is suspected, eventually cause the protein to fold incorrectly, thus forming dangerous fibrils. "However, our 3-D structure reveals that a mutated alpha-synuclein protein should not be able to form these type of fibrils," says Stahlberg. "Because of their location, most of these mutations would rather hinder the formation of the fibril structure that we have found." In brief, if the fibril structure causes Parkinson's disease, the genetic defect would have to protect against the disease. But this is not the case. So, it could be possible that a different type of fibril or another form of the protein triggers the disease in these patients.

More investigations are now needed to understand this fibril structure. What are the effects of the alpha-synuclein mutations? Do they lead to distinct forms of protein aggregates? What is the role of the fibrils for the nerve cells, and why do these cells die? To date, the exact physiological function of alpha-synuclein is still not known. Since only the symptoms of this neurodegenerative disease can be alleviated with the current medications, new concepts are urgently needed.

More information: Ricardo Guerrero-Ferreira et al. Cryo-EM structure of alpha-synuclein fibrils, eLife (2018). DOI: 10.7554/eLife.36402

Journal reference: eLife

Provided by: University of Basel

https://medicalxpress.com/news/2018-07-previous-theory-parkinson-disease.html

The Michael J. Fox Foundation for Parkinson's Research

July 5, 2018

This Sunday, July 8, Michael J. Fox will join Jane Pauley on CBS Sunday Morning to talk about his experience living with Parkinson's, as well as Fox Insight, an online clinical study where people with PD and their loved ones share information that could transform the search for better treatments. Tune in!

https://www.facebook.com/michaeljfoxfoundation/

NLY01 Is Neuroprotective In Parkinson’s Disease Mouse Model

by Florian Rosado July 4, 2018

An experimental drug that slows the progression of Parkinson’s disease itself — as well as its symptoms — in mice, has been developed by researchers at Johns Hopkins.

In experiments performed with cultures of human brain cells and live mouse models, they report the drug blocked the degradation of brain cells that is the hallmark of Parkinson’s disease. The drug is expected to move to clinical trials this year.

“It is amazingly protective of target nerve cells,”

said Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine. Dawson explained that if planned clinical trials for the drug, named NLY01, are successful in humans, it could be one of the first treatments to directly target the progression of Parkinson’s disease, not just the muscle rigidity, spasmodic movements, fatigue, dizziness, dementia and other symptoms of the disorder.

GLP1R Agonists

According to the investigators, NLY01 works by binding to so-called glucagon-like peptide-1 receptors (GLP1Rs) on the surface of certain cells. Similar drugs, called GLP1R agonists, are used widely in the treatment of type 2 diabetes to increase insulin levels in the blood.

Though past studies in animals suggested the neuroprotective potential of this class of drugs, researchers had not shown directly how it operated in the brain. To find out, Dawson and his team tested NLY01 on three major cell types in the human brain: astrocytes, microglia and neurons.

They found that microglia, a brain cell type that sends signals throughout the central nervous system in response to infection or injury, had the most sites for NLY01 to bind to — two times higher than the other cell types, and 10 times higher in humans with Parkinson’s disease compared to humans without the disease.

Dawson and his team knew that microglia secreted chemical signals that converted astrocytes — the star shaped cells that help neurons communicate with their neighbors —i nto aggressive “activated” astrocytes, which eat away at the connections between cells in the brain, causing neurons to die off. They speculated that NLY01 might stop this conversion.

“The activated astrocytes we focused on go into a revolt against the brain, and this structural breakdown contributes to the dead zones of brain tissue found in those with Parkinson’s disease. The ideas was that if we could find a way to calm those astrocytes, we might be able to slow the progression of Parkinson’s disease,”

said Dawson.

Blocking Astrocyte Conversion

In a preliminary experiment in laboratory-grown human brain cells, Dawson’s team treated human microglia with NLY01 and found that they were able to turn the activating signals off.

When healthy astrocytes were combined with the treated microglia, they did not convert into destructive activated astrocytes and remained healthy neuroprotective cells. Dawson’s team suspected that neurons throughout the body could be protected in the same way.

They explored this hypothesis by testing the drug’s effectiveness in mice engineered to have a rodent version of Parkinson’s disease.

In one experiment, Dawson’s team injected the mice with alpha-synuclein, the protein known to be the primary driver of Parkinson’s disease, and treated mice with NLY01. Similar but untreated mice injected with alpha-synuclein showed pronounced motor impairment over the course of six months in behavioral tests such as the pole test, which allows researchers to measure motor impairment such as that caused by Parkinson’s disease.

However, Dawson’s team found that the mice treated with NLY01 maintained normal physical function and had no loss of dopamine neurons, indicating that the drug protected against the development of Parkinson’s disease.

Alpha-synuclein Transgenic Mice

In a second experiment, Dawson’s team used mice that were genetically engineered to naturally produce more human-type alpha-synuclein typically used to model human Parkinson’s disease that runs in families.

Under normal conditions, these so-called transgenic mice will succumb to the disease in 387 days. However, Dawson’s team found that treatment with NLY01 extended the lives of the 20 mice treated with the drug by over 120 days.

Upon further investigation, Dawson’s team found that the brains of the mice treated with NLY01 showed few signs of the neurodegenerative characteristics of Parkinson’s disease.

Dawson cautions that the experimental drug must still be tested for safety as well as effectiveness in people, but based on the safety profile of other similar drugs, he does not anticipate any major roadblocks to its use in humans.

NLY01

Dawson says he and his team have reason to be hopeful that NLY01 could, in a relatively short period of time, make an impact on the lives of those with Parkinson’s.

Similar drugs to NLY01 already approved by the Food and Drug Administration for the treatment of type 2 diabetes include exenatide, lixisenatide, liraglutide and dulaglutide, each of which can cost approximately $2,000 for a 90-day supply. NLY01 is a long-acting drug with improved the brain penetration compared to these approved drugs for diabetes.

Parkinson’s disease is a progressive disorder of the nervous system that affects approximately 1 million people in the U.S., according to the Parkinson’s Foundation. Early symptoms include tremors, trouble sleeping, constipation and trouble moving or walking, which ultimately give way to more severe symptoms such as loss of motor function and the ability to speak, and dementia.

Most people begin showing symptoms in their 60s, but cases have been reported in patients as young as 2 years old.

The work was supported by NIH/NINDS NS38377, Maryland Stem Cell Research Foundation, the JPB Foundation, National Institute on Aging, the American Parkinson Disease Association (APDA) and the National Research Foundation of Korea.

Seung Pil Yun, et al
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Nature Medicine (2018)

https://reliawire.com/nly01-parkinsons-model/