Eradication of Helicobacter pylori Infections Could Ease Gut Symptoms, Motor Dysfunction in Parkinson’s Patients, Study Suggests

SEPTEMBER 28, 2018 BY JOSE MARQUES LOPES, PHD IN NEWS.

Eradicating Helicobacter pylori infections could improve motor function, ease gut symptoms and increase levodopa’s effectiveness in Parkinson’s patients, according to a review study.

The research, “Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease,” was published in the Journal of Parkinson’s Disease.

While a small subset of Parkinson’s cases have genetic causes, most cases are sporadic, with unknown environmental causes. Gastrointestinal symptoms such as constipation precede motor complications, suggesting that the disease might start in the gut and subsequently spread to the brain along the brain-gut axis.

This has been observed in rats, where injection of alpha-synuclein fibrils — the major component of Parkinson’s characteristic Lewy bodies — into the gut induced Parkinson’s-related pathology.

Chronic infections with H. pylori affect half the world’s population and may cause gastritis, ulcers, and stomach cancer, as well as various gastrointestinal symptoms. A greater occurrence of ulcers in patients with Parkinson’s was first reported in 1961. More recently, a link between H. pylori and Parkinson’s has been shown, with consistent reports of higher risk for Parkinson’s in people infected with this type of bacteria.

The research team reviewed all major studies that discussed the possible link between H. pylori and Parkinson’s, which led to four key findings:

• Having Parkinson’s increases by 1.5 to 3 times the risk of H. pylori infection.
• H. pylori infection worsens motor function in Parkinson’s patients.
• Eradication of H. pylori with triple therapy improved motor function in Parkinson’s patients compared to infected patients in clinical studies.
• Eradication of H. pylori improved gut absorption and increased plasma levels of Parkinson’s gold-standard treatment levodopa in patients. Research had shown that H. pylori binds to levodopa, preventing it from reaching the brain and reducing its effectiveness

As for pathways linking this bacterial infection with Parkinson’s, the researchers provided three possible explanations besides impaired levodopa effectiveness. One explanation is that bacterial toxins produced by H. pylori or alterations to the body’s own molecules such as cholesterol can damage neurons.

The infection can also cause a massive inflammatory response in the stomach, which would become systemic, cross the blood-brain barrier (BBB) — a semipermeable barrier that protects the brain — and worsen Parkinson’s symptoms and pathology. H. pyloricould also reach the brain by colonizing immune cells that cross the BBB themselves.

Finally, H. pylori may disrupt the normal gut microbial population, or microbiota, altering inflammatory mediators that predispose a person to Parkinson’s disease.

“Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship,” David J. McGee, PhD, the study’s lead author and a professor at the Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, said in a press release.

Although current evidence suggests that “eradication of H. pylori or return of the gut microflora to the proper balance in [Parkinson’s] patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction,” scientists still have little information on whether H. pylori infection “is a predisposing factor, disease progression modifier, or even a direct cause of [Parkinson’s]”, the authors wrote.

Specifically, future studies should explore the interactions of H. pylori with neurons and levodopa, the role of H. pylori toxins, how inflammatory responses to H. pylori may contribute to Parkinson’s; how these infections affect motor function, the role of the bacteria in changing the gut microbiota, and how H. pylori eradication eases Parkinson’s symptoms and improves treatment efficacy.

https://parkinsonsnewstoday.com/2018/09/28/eradication-of-helicobacter-pylori-infections-may-ease-gut-motor-symptoms-in-parkinsons-study-suggests/

A New Look at Freezing: ‘Scenario Looping Breakdowns’ As an Early Symptom

SEPTEMBER 28, 2018   DR. C'S JOURNEY WITH PD 

Reframing how we describe symptoms of Parkinson’s disease (PD) can help us understand the disease spectrum concept that I introduced last week. One such symptom is the movement disorder called “freezing.” I believe there is an early PD symptom variation of freezing, called “scenario looping breakdown.” Understanding it may help people realize what drives this symptom.

When I first heard the term freezing, I pictured a deer frozen in the headlights of a car. It wasn’t until I started experiencing subtle variations of inability to move a given muscle (it was frozen) that I understood freezing connected to something I lectured on when I worked with people who had neurological impairments. At that time, I called it, “scenario looping.”

Scenario looping is best described with a story: Imagine you’re at the grocery store to pick up dinner supplies. It’s early afternoon (no pressure) and while strolling aisles, your eyes wander about, checking people out. You see somebody vaguely familiar. The person turns to face you and your heart skips. It’s that gorgeous person you have a passionate crush on, walking to you with a big smile. Your face as red as the beets in the produce section, you smile and engage in pleasantries. The conversation turns to, “Well, what are you doing after you’re done shopping?” Every fiber in your body screams at you, “I want to spend intimate time with this person right now!” At the same time, you have in your hand a small shopping basket with spaghetti sauce, specialty meatballs, and gluten-free noodles. What do you do?

Arriving at the answer involves “looping” through the scenario over and over, weighing the consequences of any action until you arrive at a satisfactory answer of what to do. Scenarios of all types are presented to us every day. We constantly face decisions about how to use our time, how to structure our language, and even how to structure our internal dialogue. All of this connects to scenario looping.

Scenario looping also connects to motor sequencing. If you wanted to leave the spaghetti behind and immediately walk out with your old flame, then you would need to tell your body to do the necessary motor sequences. We may not think of motor sequences as part of how we interact with the day because so much of our movement, like walking, is nearly automatic.

The term “freezing” associated with PD commonly refers to freezing while walking. Walking is often automatic. We have done so much walking in our lives that it has become a motor sequence we don’t think of — an overlearned motor scenario loop. We don’t have to think about every step we take. We can run on autopilot. Think of autopilot as a small string of actions that almost automatically function in the background of your mind. If autopilot functions properly, you can simultaneously walk and have a conversation or listen to music. As the saying goes, “You can walk and chew gum at the same time.”

It is possible that scenario looping breakdowns are symptoms indicating PD’s presence. Patients often hesitate — the “breakdown” — before motor engagement. Here is an example: I finish making a PB&J sandwich and I put the jam away. I have the sandwich on a plate in my left hand. The jar of peanut butter is in my right hand, but the top to the jar sits on the counter. I want to put the peanut butter away, but for a moment I freeze, staring at the lid of the peanut butter jar on the counter. The motor steps should happen, almost without thought: Put down the plate, grab the lid, screw it on, and put the peanut butter away. I should engage in motor sequencing by scenario looping through the choices that must be made to complete the task and arrive at the desired outcome. But it doesn’t happen — there is a hesitation, a momentary freeze — a scenario looping breakdown.

(Graphic by Dr. C.)

The scenario looping breakdown should help the person with PD to understand more clearly what happens to their brain when they are freezing.

Next week: Deep fatigue is more than being tired.

***

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/2018/09/28/parkinsons-disease-new-look-freezing-scenario-looping-breakdown/

Axol's Human iPSC-derived Microglia for neuroimmunology research

September 27, 2018

Our Human iPSC-derived Microglia are suitable for a variety of applications including in vitro disease models, phenotypic screening and immunology studies.

Axol’s Microglia Maintenance Medium and Supplements have been tailored to support iPSC-derived Microglia. Providing you with an optimized culture system for the study of neuroinflammation in Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.

About Axol's hiPSC-derived Microglia

Homogenous Population. >90% pure population of TMEM119 positive microglia

Functional & Physiologically Relevant.Terminally differentiated iPSC-derived Microglia generated from human iPS cells are highly phagocytic and respond to inflammatory stimuli

Assay-Ready & Easy-to-Use. Pre-plated in 96-well plates and are ready for assay within 4 days

Axol’s Human iPSC-derived Microglia provide a reproducible, physiologically-relevant model in an easy-to-use, assay-ready format for investigating neuroglia involvement in neurodegeneration and neurodevelopment. We also offer a fully optimized serum-free Microglia Maintenance Medium to promote and support the maintenance of microglia.

Microglia are commonly described as the immune cells of the brain, with key roles in brain development, neurogenesis, synaptic plasticity and homeostatic maintenance.

Axol’s method for generating iPSC-derived microglia mimics the in vivo pathway of development for brain resident macrophages and produces microglia that are representative of primary human microglia in vitro. Our iPSC-derived Microglia deliver the advantage that they provide an almost infinite source of microglia from a single donor with a normal karyotype.

The homogenous and reproducible population of our iPSC-derived Microglia exhibit physiologically relevant functionality as they are highly phagocytic and produce cytokines in response to pathogens. Our iPSC-derived Microglia also express the microglia-specific marker TMEM119 along with myeloid markers TREM2 and IBA-1. These phenotypes make iPSC-derived Microglia suitable models for investigating neuroinflammation in Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.

Functionally validated for:

• Cytokine release

• Phagocytosis

• Efferocytosis

• Gene expression of microglia markers

• Protein expression of microglia markers

• Cell surface marker expression

• Co-culture

Source:

https://www.axolbio.com/

https://www.news-medical.net/news/20180927/Axols-Human-iPSC-derived-Microglia-for-neuroimmunology-research.aspx

Science Exchange Collaborates with Renovo Neural to Offer Novel Neurological Research Services

September 28, 2018

Science Exchange, the leading marketplace for outsourced R&D, announced today a collaboration with Renovo Neural, a Contract Research Organization (CRO) specializing in degenerative neurological conditions.

Renovo has a history in model development for multiple sclerosis (MS) and recently expanded its efforts to offer other non-clinical research services such as immunohistochemistry and 3-D electron microscopy for a wide range of neurological disorders, including Parkinson’s Disease, Alzheimer’s Disease, and Charcot-Marie-Tooth Syndrome. 

Renovo is best known for having developed an augmented cuprizone model of MS. This model – developed by the pioneering work of Bruce Trapp and Wendy Macklin – has been documented to provide superior reliability in evaluating the remyelination potential of novel therapeutic candidate compounds. Renovo has an experienced team and proven capabilities to support research and development in neurology.

“While Renovo is already well-known in the field, collaborating with Science Exchange will help expand our reach to researchers who can benefit from the technical expertise our team can provide,” stated Vivek Shenoy, CEO of Renovo. “We will be in a better position to support R&D teams actively involved in the discovery of new therapies to treat or even reverse the debilitating effects of MS and other neurodegenerative diseases.”

“We are very excited to collaborate with Renovo Neural to make its novel neurological research services readily available to scientists worldwide,” said Elizabeth Iorns, Ph.D., co-founder and CEO of Science Exchange. “Science Exchange is committed to adding the most innovative and qualified service providers to our platform, so scientists have secure, rapid access to the services they need to aid their discoveries. Renovo Neural has impressed us with their progress in the field of neurodegenerative diseases.”

About Science Exchange

Science Exchange is the world's leading marketplace for outsourced R&D, providing large R&D organizations with the fastest path from discovery through development and commercialization. Science Exchange includes an efficient source-to-secure platform for ordering 6,000+ services from a network of more than 2,500 qualified outsourced research providers, all with pre-established contracts in place that protect client intellectual property and confidentiality. The platform increases access to innovation and improves productivity, freeing scientists from administrative tasks and delays associated with sourcing, establishing and managing service provider contracts. 

Additionally, the Science Exchange enterprise program enables large R&D organizations to consolidate research outsourcing spend into a single strategic relationship, driving efficiency, improving transparency and oversight, and delivering cost savings. Since being founded in 2011, Science Exchange has raised more than $58 million from Norwest Venture Partners, Maverick Capital Ventures, Union Square Ventures, Collaborative Fund, Index Ventures, OATV, the YC Continuity Fund, and others. For more information, visit www.ScienceExchange.com. 

About Renovo Neural

Renovo Neural, Inc. is a private CRO operating in Cleveland, Ohio, for the past 10 years. The company was co-founded by Dr. Wendy Macklin and Dr. Bruce Trapp, Chief Scientific Officer of Renovo and the current chair of the Neuroscience Department at the Lerner Research Institute at the Cleveland Clinic. Drs. Macklin and Trapp are both recognized as world-renowned experts in Multiple Sclerosis research. The company offers pre-clinical / non-clinical translational research services with a focus on the evaluation of neuro-therapeutics.

View source version on businesswire.com: https://www.businesswire.com/news/home/20180928005063/en/

Contacts

Science Exchange

Gursatya "Guru" Singh

Director of Scientific Content

marketing@scienceexchange.com

or

Renovo Neural, Inc.

Chris Ryan, +1 216-445-4202

Executive Director, Business Development

CRyan@RenovoNeural.com

The information on this page is provided by Business Wire. All rights reserved. Reproduction or redistribution of this content without prior written consent from Business Wire is strictly prohibited. L.A. Biz is not responsible for this content. 

https://www.bizjournals.com/losangeles/businesswire/press_releases/California/2018/09/28/20180928005063

Who Says You Need Permission to Study Yourself?

Emily MullinSep 27, 2018

Sara Riggare can’t finish her PhD because an ethics committee says she needed their approval first.

The authorities say scientist Sara Riggare should have obtained ethical approval for her work — even though she is her own research subject. Illustration by Calum Heath

For the past six years, Sara Riggare, who has Parkinson’s disease, has been conducting research on herself as part of her PhD at the prestigious Karolinska Institute in Sweden. Using mobile apps, she tracks her symptoms, sleep, and activity.

She’s not unique in doing so: Many people self-monitor with apps and wearable devices like Fitbit and the Apple Watch, a trend spurred by the broader Quantified Self movement, where “lifeloggers” track everything from their blood sugar to their microbiome, and even carry out experiments on themselves.

But Riggare goes further than most in using her self-experimentation to contribute to science — including publishing studies on herself. In one study in the Journal of Parkinson’s Disease, she describes using a smartphone app that measures finger-tapping speed to evaluate how the effects of her Parkinson’s medications vary over the course of the day. For another peer-reviewed study, she vaped with an e-cigarette, then tracked and analyzed the effects of nicotine on her Parkinson’s symptoms. She gleaned important health insights from both studies, including that nicotine seemed to decrease the involuntary movements that are a common side effect of one drug.

But earlier this month, Riggare was told by a dissertation committee that she wouldn’t be able to defend her PhD in November as planned. The reason? She didn’t get approval from an ethics committee prior to conducting these studies. No law explicitly prevents her from experimenting on herself as a private person, but her dissertation committee interpreted a Swedish law called the Ethical Review Act to mean that she should’ve first obtained that permission because her experiments are considered research.

“The Swedish law on ethical review states that research on human beings with the intention to affect a research person physically may only be conducted after acquiring ethical permit,” the Karolinska Institute said in a statement provided to NEO.LIFE. “The reason is that research subjects must be protected. As a PhD student, Sara Riggare is part of a research group that includes her supervisors. The research group may not perform experiments on human beings without ethical permit, even if the person is one of its members.”

Should anyone have the power to prevent people from experimenting on themselves — or be able to deny credit for the science that self-experimenters produce?

In other words, the dissertation committee considered the two studies she had done toward her degree inadmissible. The Karolinska Institute requires that doctoral students publish at least two papers in peer-reviewed journals before they can defend their thesis. If Riggare can’t get retroactive approval for her research, she’ll have to do more research, which could take years.

Riggare was disappointed. (She announced the ruling on public Facebook and blog posts, but declined to make herself available for an interview, citing her health and workload.)

In an era of empowered patients and DIY scientists who constantly collect data about themselves on apps and smart devices, patient-driven research raises important questions. Should anyone have the power to prevent people from experimenting on themselves — or be able to deny credit for the science that self-experimenters produce?

“Of course we as a society need to ensure that all medical research is conducted in an ethical manner,” Riggare wrote in her post. “We also have a collective responsibility to ensure that our rules and regulations are appropriate for the day and age we live in.”

Who experiments on who?

Medical research actually has a long history of self-experimentation. And in many cases, it’s been heralded. Werner Forssmann, who performed the first heart catheterization on himself, and Barry Marshall, who gave himself ulcers in order to prove they were caused by bacterial infection, both won Nobel Prizes for their extreme experiments.

At the world-renowned Karolinska Institute, Nobel Prize winners give their talks at the Aula Medica lecture hall. Image by Ainali/Wikipedia

Since the 1970s, though, the research world has moved to a system in which studies involving human subjects need to be first reviewed and approved by an ethics committee. This requirement was designed to prevent abuses committed under the guise of medical research, like the Tuskegee experiment, in which African American men with syphilis were deliberately left untreated.

In the U.S., an institutional review board or IRB has the authority to approve or veto a study, or ask for modifications; other countries have their own versions. Their purpose is to protect human participants. One way they do that is by making sure researchers provide volunteers with clear information about any risks in the study, and get the participants’ informed consent — that is to say, the participants fully understand what they’re getting into and agree to it anyway.

“The whole reason that ethics boards exist is because of the information asymmetry in research,” says Mad Price Ball, executive director of the Open Humans Project, a platform that allows you to upload, connect and store your health data. That asymmetry means that volunteers typically know much less about the risks than the researchers do.

Self-experimentation, however, changes the formula. In this case the researcher who knows the most about the study is also the study’s volunteer.

“When the researcher and the participant are one and the same, the idea that they are not adequately informed but that some ethical committee is, I think is silly,” says Michelle Meyer, a bioethicist and lawyer at Geisinger Health System in Pennsylvania.

Under some circumstances, she notes, self-experimentation can raise ethical concerns. For example, graduate students could possibly feel pressure to do research on themselves to get published or do a dissertation.

“You could imagine the principal investigator of a lab saying, ‘We’re all going to test this on ourselves,’” she says. “Just because they’re all co-investigators on a study doesn’t mean that there can’t be power differentials that could be troubling.”

There’s a real concern that the science produced by people like Riggare will be lost, says Mad Price Ball.

Christian Munthe, professor of practical philosophy at the University of Gothenburg in Sweden and a member of the delegation for medical ethics of the Swedish Society of Medicine says he agrees with the Karolinska Institute’s review of Swedish law. However, he says, “the legal fault formally falls on the head of department for the unit where the candidate’s research was undertaken. It is, furthermore, good reason for the candidate to demand and get compensation in the form of extended PhD funding for the lost time, so that she can finish her PhD training in a proper manner.”

In the U.S., Meyer says, many IRBs have taken a similar position: if you’re doing research and it involves human subjects, you are a human subject even if you’re also the researcher.

“I think the conversation is about whether that’s an appropriate policy or not,” says Meyer, adding that IRBs weren’t designed with self-experimentation in mind.

Ball expects that other scientific self-experimenters, including in the U.S., could also be denied credit for their work, and worries it could encourage “senseless risk aversion” in research. Plus, Ball says, there’s a real concern that the science produced by people like Riggare will be lost: “When knowledge has been gained, should you really decide to toss a whole body of work into the dumpster? That’s a serious ethical question.”

https://medium.com/neodotlife/who-says-you-need-permission-to-study-yourself-1c347a25c10c

Is coffee good for you?

September 28, 2018

At just a couple of calories a cup, good old black coffee packs quite a punch. It wakes you up, boosts your metabolic rate and decreases the risk of some diseases.

Not that habitual coffee drinkers need convincing, but evidence of its health benefits stacks up quickly:

• It gives you energy and may help you lose weight and sharpen your mental focus, thanks to the magic of caffeine. Studies have shown that caffeine may improve your mood, help your brain work better and improve performance during exercise.
• A regular java habit is associated with a lower risk of Type 2 diabetes and Parkinson's disease. Additionally, in one study, caffeine was linked to a lower risk of Alzheimer's disease.
• Coffee is an excellent source of antioxidants, which may help protect cells from damage.
• Higher consumption of coffee—caffeinated and decaf alike—was associated with a lower risk of total mortality, including deaths attributed to heart disease, nervous system diseases and suicide. More specifically, habitual coffee drinking has been linked to a lower risk of coronary heart disease in women.

For health-conscious coffee lovers then, the most important question isn't, "Is it good for you?" but rather, "How do you take it?"

If you dress your coffee up too much with cream and sugar, you risk negating the health benefits.

"We know that sugar has adverse effects," said Penny Kris-Etherton, a nutrition professor at Penn State University. "Even if you add sugar and don't exceed your calorie needs, you're still negating some of the benefits because sugar is a negative food ingredient."

That warning goes double for even fancier coffee drinks. The federal dietary guidelines say three to five cups of coffee per day can be part of a healthy diet, but that only refers to plain black coffee.

"They're not talking about these large Frappuccinos that have at least 800 calories a beverage," Kris-Etherton said. "Very quickly, calories can add up, and weight gain will create negative effects on cardiac risk."

Despite its benefits, caffeine also can be dangerous if consumed in excess. 

"We all know how important sleep is," Kris-Etherton said. "You don't want to disrupt normal sleep habits and good sleep because you've had too much caffeine, so if you want to include coffee in your diet, be sure to think about timing."

Anyone who's had one cup too many knows that heart-fluttering feeling that comes next; for some people, those jitters may be a warning sign.

"Some people are slow metabolizers of caffeine," Kris-Etherton said. "It's a genetic predisposition. Some people can experience jitters, palpitation, insomnia sort of like those energy drinks that give you a big boost."

Caffeine also is addictive, and cutting back too quickly can cause withdrawal symptoms, especially terribly harsh headaches.

"Those migraines are pretty bad," she said. "If you are drinking a lot and then go cold turkey, the effects will be greater than if you have less caffeine and taper off."

It's worth noting that kids shouldn't drink coffee, Kris-Etherton said. The American Academy of Pediatrics recommends that, in general, kids avoid caffeine-containing beverages.

Kris-Etherton also cautioned that brewing methods can affect cardiovascular risk. For example, she said, paper filters remove a compound called cafestol that increases LDL cholesterol (the harmful type), so unfiltered coffee could pose a higher health risk.

"Most people drink filtered coffee," she said. "But you know, French presses are so popular too, and that may not be good for you, especially if you drink a lot of coffee."

Still, Kris-Etherton said, research shows that the health benefits of coffee—even decaf—seem to outweigh the risks: "Just pay attention to how you're feeling after consuming coffee. Get in sync with how your body's feeling."

https://medicalxpress.com/news/2018-09-coffee-good.html

Catalent selected to provide oral delivery systems for GB Sciences

27-Sep-2018 

The partnership will tackle the first-ever formulations of APIs containing up to nine cannabinoids and terpenoids for the treatment of Parkinson’s disease

GB Sciences and Catalent Pharma Solutions, a provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products, has announced that GB Sciences has selected Catalent to provide oral delivery systems, formulation development and clinical-scale oral dose manufacturing of GB Sciences’ proprietary APIs for its Parkinson’s disease therapies. 

A proof of concept study will be conducted by Catalent at its Swindon, UK facility to evaluate GB Sciences’ clinical candidates GBS101, GBS102 and GBS103 using Catalent’s proprietary Zydis Orally Disintegrating Tablet (ODT) technology.

GB Sciences’ three patent-pending APIs for Parkinson’s disease are complex mixtures containing up to nine individual components that function synergistically. Preclinical studies have shown that these cannabinoid-containing complex mixtures are more potent than would have been predicted by combining the activity of each individual compound.

“To prepare our Parkinson’s disease formulations for human clinical trials, we wanted the ease-of-use offered by Zydis ODTs for our Parkinson’s patients, many of whom may have difficulties in swallowing. Catalent’s proprietary delivery method also potentially offers consistent dosing for our complex cannabinoid and terpenoid-containing APIs,” explained Dr Andrea Small-Howard, Chief Science Officer of GB Sciences. 

“The creation of GB Sciences’ proprietary APIs in Zydis ODT formulations is a very important step towards readying them for our Exploratory IND filing and planned phase zero human trial for patients with mild to moderate Parkinson’s disease.”

Jonathan Arnold, President of Oral Drug Delivery at Catalent, added: “Dissolving rapidly in the mouth, ODTs are convenient and ease administration, offering an alternate dosage form for patients who have difficulty swallowing, as is sometimes the case with Parkinson’s disease, as well as with geriatric or pediatric patients.” 

GB Sciences selected Catalent as its development partner due to its expertise in tackling formulation challenges, and ability to achieve the stability and dosing necessary for these novel complex mixtures.

Catalent has early development and oral drug delivery solutions available for the efficient delivery of GB Sciences’ proprietary APIs.

https://www.manufacturingchemist.com/news/article_page/Catalent_selected_to_provide_oral_delivery_systems_for_GB_Sciences/147512

Early Parkinson's patients waiting too long to seek medical evaluation

 September 27, 2018, University of South Florida

Figure 1. Relationship between time of diagnosis, need for symptomatic therapy and the opportunity for a patient to participate in an early PD disease modifying therapy trial. Credit: University of South Florida

The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson's Disease (PD). A paper published in Nature Partner Journal: Parkinson's Disease notes too many early PD patients wait too long before seeking medical attention, or start taking symptomatic medications before they are required, thereby dramatically shrinking the pool of candidates for clinical trials.

Parkinson's disease is a disorder of the central nervous system that affects movement. Symptoms include tremors, stiffness, and slow and small movement. The pace of progression varies among patients, making the months following diagnosis crucial to researchers studying the disease's progression.

"The critical time of about one year from when the patient can be diagnosed with early PD based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year," said lead author Robert A. Hauser, MD, director of the Parkinson's & Movement Disorder Center at the University of South Florida. "It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease."

Hauser says that in order to determine whether or not a potential disease slowing therapy is actually working, they must be able to compare the therapy to a placebo without interference from symptomatic treatment. Otherwise, they won't know if the therapy is slowing the disease's progression or if they are just seeing the effects of symptomatic treatment.

This requires patients to seek assessment soon after they notice the onset of tremor or slow movement. In addition, physicians should consider referring patients to clinical trials soon after diagnosis and delay prescribing symptomatic medication until it's necessary. If a patient waits until symptomatic treatment is necessary, the opportunity to participate in these crucial clinical trials is lost.

More information: Robert A. Hauser. Help cure Parkinson's disease: please don't waste the Golden Year, npj Parkinson's Disease (2018). DOI: 10.1038/s41531-018-0065-1

https://medicalxpress.com/news/2018-09-early-parkinson-patients-medical.html

Researchers evaluate controversial treatment for Parkinson's disease psychosis

September 26, 2018, University of California - San Diego

In the wake of media and public reports about increased mortality linked to a new drug for treating Parkinson's disease psychosis (PDP)—a symptom of the progressive nervous system disorder in which patients experience hallucinations and delusions—researchers at University of California San Diego School of Medicine conducted a retrospective study of qualifying patients in the UC San Diego Health system, concluding that the new drug, pimavanserin (marketed as Nuplazid), did not pose a statistically significant greater risk of death.

The findings are published in the September 26 online issue of Neurology.

"This paper is important because pimavanserin has been in the news, and there is considerable debate and concern about its safety," said Fatta B. Nahab, MD, associate professor in the Department of Neurosciences at UC San Diego School of Medicine and the study's corresponding author. "We wanted to better understand and assess the risks of using pimavanserin within our own patient community, either alone or in combination with other commonly prescribed medications."

Parkinson's disease (PD) is a complex neurodegenerative disorder. Symptoms generally develop slowly over years, and typically affect movement, balance and walking. However, cognitive dysfunction, such as PDP, often appears in the latter stages of the disease and is a leading contributor to patients being placed in nursing homes.

PD itself is not fatal, but it is associated with serious disease complications, making the condition the 14th leading cause of death in the United States, according to the Centers for Disease Control and Prevention.

Using anonymized medical records of 4,478 UC San Diego Health patients with a diagnosis of Parkinson's disease, Nahab and colleagues singled out 676 cases that met the study criteria of having a PD diagnosis and being prescribed pimavanserin, quetiapine (an antipsychotic drug marketed as Seroquel) or both medications between April 29, 2016 and April 29, 2018. 

The Food and Drug Administration approved Nuplazid for PDP in April 2016 after designating it a "breakthrough therapy." The expedited approval followed a single, six-week clinical trial of 199 participants. The drug is marketed by Acadia Pharmaceuticals, Inc., based in San Diego.

As the first drug approved to treat hallucinations and delusions associated with PDP, Nuplazid was immediately popular, with sales exceeding $100 million in 2017. But lingering concerns about limited clinical testing were exacerbated by reports of increased adverse effects in patients using pimavanserin, "including deaths, life-threatening incidents, falls, insomnia, nausea and fatigue," according to an April 9, 2018 story by CNN.

In their review of the 676 qualifying patient cases, UC San Diego researchers found a lower mortality percentage for those using pimavanserin compared to those using only quetiapine or those using both drugs. "But the differences were not significant," said Nahab.

The researchers did note a significant increased risk of mortality—74 percent—in the quetiapine-only group compared with individuals not on these medications and a trend toward increased risk in the combination therapy group. "It's reasonable to assume, however, that individuals requiring these medications have greater diseaseseverity and are at a higher risk of complications and death," said Nahab.

"Our findings provide the largest comparative report of mortality risk in PDP to date," said Nahab, "but there were limitations to our study based on its design and nature. We did not find any new or unexpected concerns about the use of pimavanserin in the treatment of PDP, which may provide some reassurance to clinicians, patients and families. But more work is needed to better evaluate factors like disease severity and cause of death to improve our understanding of the potential risks of treating PDP."

More information: Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine, Neurology (2018). DOI: 10.1212/WNL.0000000000006396 , http://n.neurology.org/content/early/2018/09/26/WNL.0000000000006396

Journal reference: Neurology

Provided by: University of California - San Diego

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