Scientists to use iPS cells to develop method to treat Parkinson's disease

The Asahi Shimbun

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By AKIYOSHI ABE/ Starff Writer

Researchers at Kyoto University are set to begin clinical studies, possibly as early as next year, to verify a cell replacement therapy that uses human induced pluripotent stem (iPS) cells to treat Parkinson’s disease.

It would be the first time for nerve cells developed from iPS cells to be transplanted into the human brain.

The team at the university’s Center for iPS Cell Research and Application (CiRA), headed by stem cell pioneer Shinya Yamanaka, will apply for the project's approval in June from a review committee to be created within the university.

If the cell replacement therapy is proven to be effective, it could lead to the discovery of a cure for the degenerative disorder of the central nervous system. There currently are about 150,000 patients with Parkinson’s disease in Japan.

Parkinson’s disease damages dopamine-producing nerve cells, or neurons, in the brain. Although symptoms of the disease can be treated with conventional medicine, there is no cure for Parkinson’s.

Scientists are investigating how cell replacement therapy could be used to treat the disease. Clinical trials to transplant healthy nerve cells taken from deceased infants into patients’ brains have been performed overseas.

But the efficacy of such treatment has not been authenticated because of the difficulty of obtaining a sufficient amount of healthy nerve cells. Also, donated cells contain a variety of cells that are not dopamine-producing neurons.

According to a project developed by Jun Takahashi, a professor of neurosurgery at CiRA, the team will produce dopamine-producing nerve cells from iPS cells that are created from a patient’s own cells.

The synthetic neurons will then be injected into the central area of the patient’s brain at a precise location.

The main purpose of the project is to determine if such cell replacement treatment can be damaging to a patient’s health. But if the transplanted neurons function effectively, they could halt progress of the disease’s symptoms.

Because unwanted neurons can be produced in the process of formulating synthetic cells, the team has already developed a method to sort out useful neurons from a large amount of nerve cells. Animal tests have already proven the effectiveness of the neuron-screening method.

Transplanted iPS cells can also multiply prolifically in the human body and cause cancer and other tumors when they are transplanted before they develop into specific types of cells.

To confirm the safety of the transplantation of iPS-originated cells, a team of researchers at the Riken Center for Developmental Biology is currently conducting the world’s first clinical study to transplant retina cells produced from iPS cells into patients’ eyes.

Unlike retina cell transplantation, the transplantation of neurons in human brains will require image diagnostic methods, including magnetic resonance imaging (MRI), to observe the effectiveness of the treatment.

Kyoto University’s review committee will take six months or longer to discuss safety measures for the observation methods and other issues before approving the clinical trial for Parkinson’s disease treatment.

After it obtains the committee’s approval, the research team will begin preparation for producing iPS-originated nerve cells to be used in clinical tests. If the clinical trials deliver the expected results, the team plans to apply for further clinical trials based on the pharmaceutical and medical device law so that the treatment will be applicable to insurance.

http://health.einnews.com/article/265757930/DPMY8cLhvbBrlR9w

Parkinson's disease increasing, but so are better treatments

Friday, May 15, 2015

JON-MICHAEL SULLIVAN/STAFF

Dr. David Standaert, professor and chair of neurology at the University of Alabama at Birmingham, gives a presentation during the "Know More; Live More: Parkinson's 101" event presented by the Georgia Regents Neuroscience Center held at the Kroc Center in Augusta.

There is a “tsunami” of new Parkinson’s disease cases that will hit the U.S. in coming years as the population ages overall, an expert told the audience at a Georgia Regents Health System forum on Friday.But better treatments and new insights into the way damage may spread in the brain could help stem that tide.

Dr. David Standaert, director of the Center for Neurodegeneration and Experimental Therapeutics at the University of Alabama at Birmingham, spoke to a forum for patients and caregivers hosted by Georgia Regents Neuroscience Center.

Risk for Parkinson’s increases with aging, with an average of one case per 100 at age 65 but two or three per 100 at age 85, he said. With the Baby Boomer population just now hitting their 60s, the number of people with Parkinson’s is expected to increase from 1.5 million now to 4 million within the next 25 years, Standaert said.

“We’re going to see a tsunami of Parkinson’s disease as a result of the aging of the population,” he said. “We need to have better treatments for this or we’re going to have a very serious problem.”

Parkinson’s patients have long had treatments that can really help them, notably the drug levadopa and carbidopa, and more recently electrical deep brain stimulation, which makes it different from many other neurodegenerative diseases, Standaert said.

In the last year, it has seen three new treatments, including a gel form for levadopa and carbidopa delivered by an infusion pump directly into the gastrointestinal tract that can provide a “leveling out” of drug relief for patients, Standaert said.

But future treatments could come from a better understanding of not only what causes Parkinson’s disease but what really causes the damage and makes the disease progress from year to year. An excess of a particular 

protein called alpha-synuclein is known to accumulate in the brains of Parkinson’s patients and is thought to misfold and clump together, similar to what is thought to happen in the brains of Alzheimer’s patients with another type of protein.

Standaert and others believe these clumped, misfolded proteins can travel through the brain and cause an inflammatory reaction there.

“Synuclein is the upstream culprit of the thing that actually is killing neurons and producing the damage,” he said. While there are other causes, from genetics to the environment, of why people start to develop Parkinson’s, “I think once you trigger that, then that’s where inflammation becomes important,” Standaert said. “The cause is upstream but inflammation is what makes it worse from year to year.”

There are other diseases where there are drugs to fight an improper immune response in the brain, such as lupus or multiple sclerosis, so even if the cause is different some of the treatments might eventually be beneficial, he said.

“I think there could be a convergence in treatments, absolutely,” Standaert said.

His own lab has used a mouse model to knock out a key immune protein that found where synuclein was not toxic to those animals. While that is not possible in humans, Standaert’s lab has targeted the gene that controls that protein and has a grant from the Michael J. Fox Foundation for Parkinson’s Research to explore whether that could be a target for interventions.

But part of the problem will also be just getting the correct diagnosis in the first place.

Marilyn Sullivan, of Aiken, noticed years before her husband, Robert, was diagnosed with Parkinson’s that he was shuffling his feet and she was having trouble hearing him. She bought him new shoes and took him around to different specialists before he was finally diagnosed two years ago.

“No one ever mentioned Parkinson’s,” she said. Dr. Kapil Sethi, director of the Georgia Regents Movement Disorders Program, told her she shouldn’t feel bad it took so long.

“You did your job,” he said. “It’s a common problem” with the diagnosis.

http://health.einnews.com/article/265709286/cDuNcheGGHypvWKC

A LITTLE TIDBIT OF INFORMATION

OUGH & GAG: Oh, that pesky phlegm!

Sherryl Klingelhofer

September 17, 2012 at 11:10am

Dad had so much trouble with it, and I know others who do, too...

Here’s an idea if you are already dealing with this common Parkinson’s problem! 

We had a Physical Therapist show us an exercise to help the body "remember" how to swallow that helped Dad clear his throat a bit.  Doesn't get RID of the phlegm, but made it easier to deal with.

• SIT UPRIGHT---make sure the head is over the torso and the torso is not leaning back or in a concave shape that would curve the esophagus or compromise the entry in the throat.  If needed, put a small pillow or rolled towel behind the spine against the back of the chair to assist upright posture!

• Cough.  Drink a SIP of water.  Cough. (you may need to swallow---do so with or without the sip of water)

• Wait and repeat about half a dozen times.  Do this a couple times daily in between meals, but also try it BEFORE eating to jump start the brain...

That laying back in a bed or lounge chair is a real booger (we might just as well stay in icky-mode)!  It lets the phlegm sit right on the "swallower", so positioning is really important!  Next time you start the choking, shove your hips back into the chair and lean slightly forward to cough/swallow.

…………………………
You can practice opening and closing the throat if swallowing is being compromised!  And since you never think about keeping the muscles in the throat active, until after the fact, begin these now to avoid future issues!

• Say “X” then “R” several times (yes, out loud so it can be heard!)---do it slowly and pretend you telling someone how to enunciate and say them correctly!

• Say “QUICK-QUACK-QUIRK” several times as above

• Make a fire engine noise by saying (loudly!)  “rrr-RRR-rrr-RRR-rrr-RRR” and make it go up and down as they do:  you will feel your throat at work!

Nerve cells in the fast lane

Last updated: Friday 15 May 2015 at 12am PST 

Dopamine-producing neurons  important function in the brain

Nerve cells that produce dopamine for the purpose of transmitting signals to other cells affect numerous crucial brain functions. This becomes evident in diseases such as Parkinson's and schizophrenia, where dopamine transmission in the brain is impaired. In collaboration with researchers from Bonn, RUB scientists at the Mercator Research Group "Structure of Memory" have now identified in what way a specific form of this important cell is generated and which networks it forms in the course of brain development. In the process, the researchers discovered a data highway of sorts: the nerve cells use not only dopamine for signal transmission, but also the much-faster glutamate. The results have now been published in the trade magazine Nature Neuroscience.

Crucial role in signal transmission

Dopamine-producing neurons fulfil a crucial role in signal transmission: as the brain develops, they mature into several specialised subtypes, which, acting as a kind of networkers, generate synapses to other important brain regions. Their name derives from the fact that they utilise dopamine as a messenger. This neurotransmitter is very important: it affects, for example, motor control, reward behaviour, motivation and impulse control. Symptoms of diseases such as Parkinson's and schizophrenia include dying of dopamine neurons resp. disruption of dopamine signal transmission.

Glutamate facilitates rapid signal transmission

In collaboration with colleagues from the German Center for Neurodegenerative Diseases (DZNE), the Life & Brain Center Bonn and the Mercator Research Group "Structure of Memory", scientists at Bonn University discovered a data highway of sorts in the animal model. While dopamine-aided signal transmission between neurons is relatively slow, the analysed dopamine-producing neurons have additionally used glutamate as a messenger.

Researchers excited single nerve cells with light stimuli

Using genetic-engineering methods, the researchers coupled the dopamine-producing neurons of mice with light-sensitive proteins. Thus, they were able to excite individual dopamine-neurons with light stimuli and track the signalling pathways. With the aid of glutamate, locally inhibiting neurons were activated in the prefrontal cortex, a control centre in the brain. These, in turn, are responsible for the regulation of signal transmission in the prefrontal cortex: they are involved, for example, in deciding if a signal should be forwarded. In order to identify in what way different subtypes of dopamine-producing neurons are generated, the researchers muted one gene in mice. Thus, the formation of dopamine-neurons in the prefrontal cortex was suppressed.

Mice had to nudge a blinking light

What were the consequences of the lack of dopamine-producing cells? Together with the team headed by Prof Dr Magdalena Sauvage from Ruhr-Universität Bochum, the researchers from Bonn tested this in attention experiments. Mice were rewarded with food if they nudged a rapidly blinking light as quickly as possible. "The results have shown that animals in which the dopamine-producing cells had been genetically switched off didn't demonstrate any apparent changes to their attention and impulse control, but they pursued acquired behaviour patterns much more persistently," says Prof Sauvage. A pathological clinging to certain notions or repeating words and movements in an unsuitable context does also occur in mental disorders such as obsessive-compulsive disorder or schizophrenia, where the function of the prefrontal cortex is disturbed. Accordingly, the results of the research cooperation contribute to an improved understanding of the development and function of dopamine-producing neurons and possibly the diseases related thereto.

http://www.medicalnewstoday.com/releases/293853.php?tw

Amarantus Announces Successful Delivery and Distribution of MANF in Preclinical Model to Brain Areas Involved in Parkinson's Disease

SAN FRANCISCO and GENEVA, May 15, 2015 (GLOBE NEWSWIRE) 

-- Amarantus BioScience Holdings, Inc. (OTCQB:AMBS), a biotechnology company focused on developing therapeutic and diagnostic products for neurological disorders and orphan indications, announced that it has completed a study of mesencephalic-astrocyte-derived neurotrophic factor (MANF) administration to the putamen and the substantia nigra of pigs by convection-enhanced delivery. This study generated MANF brain delivery and distribution data, further supporting the rationale for MANF's development in the treatment of Parkinson's disease (PD). The study was conducted in the United Kingdom in collaboration with Renishaw plc's (LON:RSW) Neurological Applications Department and its leading academic partner, Functional Neurosurgery Research Group at the University of Bristol.

In previously reported studies, MANF has been demonstrated by multiple laboratories to be neuroprotective and neurorestorative in rat models of Parkinson's disease. The current study demonstrated that: (i) MANF can be delivered to the porcine putamen and substantia nigra, brain areas centrally involved in PD, and (ii) that pharmacologically efficacious levels are achieved using Renishaw's convection-enhanced delivery device currently in human clinical development. The porcine brain is considered a good model to evaluate the feasibility of delivering therapeutic agents to the human brain, as it has a significantly larger brain volume than that of a rat or non human primate (NHP). These data demonstrating accurate surgical targeting and distribution of MANF mark an important step in the development of MANF for the treatment of PD.

"We are very encouraged by this important set of data demonstrating that MANF can be delivered to the brain with great accuracy," said Gerald E. Commissiong, President & CEO of Amarantus. "MANF was precisely delivered to sites of the brain affected by Parkinson's disease and the volume of distribution was thought to be sufficient to elicit a treatment effect. This data further positions Amarantus in the Parkinson's disease space, as we are preparing to initiate our Phase 2b small molecule program of our lead product candidate, eltoprazine, in Parkinson's disease levodopa-induced dyskinesia and continue with the development of MANF as a potential disease-modifying treatment for PD."

In the study single bilateral catheters were implanted into the putamen and the substantia nigra, respectively. High accuracy to within 0.5 mm of the planned target was demonstrated by post-operative magnetic resonance imaging (MRI) while infusing Gadolinium-DTPA (Gd) during real-time scanning. MANF was administered to the porcine brain target sites 14 days later by convection-enhanced delivery. No evidence of reflux was detected. Immuno-staining on serial axial and coronal sections combined with volumetric analysis demonstrated MANF distribution volumes of 307 mm³ and 105 mm³ for the putamen and the substantia nigra, respectively. The observed distribution in porcine putamen was comparable to the one required to elicit neuroprotection in the rat PD model. Moreover, MANF and Gd distribution volumes correlated well and Gd did not appear to alter MANF's pattern of distribution. The Company believes these data provide a firm basis for studies in NHPs as well as subsequent human clinical trials.

The Company expects to publish further data from this study in peer-reviewed journals and at scientific congresses over the course of 2015.

About Parkinson's Disease

Parkinson's disease is a chronic, progressive neurological disorder that causes motor symptoms such as tremors, rigidity and slowed movements as well as non-motor symptoms including cognitive impairment and autonomic dysfunction. The Parkinson's Disease Foundation estimates that there are approximately one million people living with PD in the United States and seven to ten million PD patients worldwide. The most commonly prescribed treatments for PD are levodopa-based therapies. There is currently no cure available for Parkinson's disease.

About Mesencephalic-Astrocyte-derived Neurotrophic Factor (MANF)

MANF (mesencephalic-astrocyte-derived neurotrophic factor) is believed to have broad potential because it is a naturally-occurring protein produced by the body for the purpose of reducing and preventing apoptosis (cell death) in response to injury or disease, via the unfolded protein response. By manufacturing MANF and administering it to the body, Amarantus is seeking to use a regenerative medicine approach to assist the body with higher quantities of MANF when needed. Amarantus is the front-runner and primary holder of intellectual property around MANF, and is initially focusing on the development of MANF-based protein therapeutics. MANF, a naturally-occurring protein that reduces and prevents apoptosis (programmed cell death) in response to injury or disease, was discovered utilizing Amarantus' proprietary PhenoGuard^™ Protein Discovery Engine.

MANF's lead indication is retinitis pigmentosa, and additional indications including Parkinson's disease, diabetes and Wolfram's syndrome are currently being pursued. Further applications for MANF may include Alzheimer's disease, traumatic brain injury, myocardial infarction, antibiotic-induced ototoxicity and certain other rare orphan diseases currently under evaluation.

About Amarantus BioScience Holdings, Inc.

Amarantus BioScience Holdings (AMBS) is a biotechnology company developing treatments and diagnostics for diseases in the areas of neurology, psychiatry, ophthalmology and regenerative medicine. AMBS' Therapeutics division has development rights to eltoprazine, a Phase 2b ready small molecule indicated for Parkinson's disease levodopa-induced dyskinesia, adult ADHD and Alzheimer's aggression, and owns the intellectual property rights to a therapeutic protein known as mesencephalic-astrocyte-derived neurotrophic factor (MANF) and is developing MANF-based products as treatments for brain and ophthalmic disorders. AMBS' Diagnostics division owns the rights to MSPrecise^®, a proprietary next-generation DNA sequencing (NGS) assay for the identification of patients with relapsing-remitting multiple sclerosis (RRMS) at first clinical presentation, has an exclusive worldwide license to the Lymphocyte Proliferation test (LymPro Test^®) for Alzheimer's disease, which was developed by Prof. Thomas Arendt, Ph.D., from the University of Leipzig, and owns intellectual property for the diagnosis of Parkinson's disease (NuroPro). AMBS also owns the discovery of neurotrophic factors (PhenoGuard^™) that led to MANF's discovery.

For further information please visit www.Amarantus.com, or connect with the Company on Facebook, LinkedIn, Twitter and Google+.

Forward-Looking Statements

Certain statements, other than purely historical information, including estimates, projections, statements relating to our business plans, objectives, and expected operating results, and the assumptions upon which those statements are based, are forward-looking statements. These forward-looking statements generally are identified by the words "believes," "project," "expects," "anticipates," "estimates," "intends," "strategy," "plan," "may," "will," "would," "will be," "will continue," "will likely result," and similar expressions. Forward-looking statements are based on current expectations and assumptions that are subject to risks and uncertainties which may cause actual results to differ materially from the forward-looking statements. Our ability to predict results or the actual effect of future plans or strategies is inherently uncertain. Factors which could have a material adverse effect on our operations and future prospects on a consolidated basis include, but are not limited to: changes in economic conditions, legislative/regulatory changes, availability of capital, interest rates, competition, and generally accepted accounting principles. These risks and uncertainties should also be considered in evaluating forward-looking statements and undue reliance should not be placed on such statements.

Investor and Media Contact:
Jenene Thomas
Jenene Thomas Communications, LLC
Investor Relations and Corporate Communications Advisor
T: (US) 908.938.1475E:

- See more at: http://globenewswire.com/news-release/2015/05/15/736287/10134645/en/Amarantus-Announces-Successful-Delivery-and-Distribution-of-MANF-in-Preclinical-Model-to-Brain-Areas-Involved-in-Parkinson-s-Disease.html?f=22&fvtc=3&fvtv=4000#sthash.vEQmLOOU.dpuf

http://health.einnews.com/article/265601829/AfTvGVLtyHuOc4df

Genentech Brain Trust Leaves With $217 Million For New Startup To Fight Alzheimer's And Parkinson's

Marc Tessier-Lavigne

Three former top researchers at Genentech , the legendary biotech that is now part of Roche Holding , have raised $217 million in venture capital to start a new company, Denali Therapeutics, focused on treating and curing neurodegenerative diseases like Alzheimer’s, ALS, and Parkinson’s.

The news is another sign of both the large amounts of money available to all biotechnology startups and for a financial turnaround for research efforts against brain diseases that have been tough to beat. NeuroPerspective, a newsletter that tracks neurological treatments, says in the past five years the number of drugs being developed by large drugmakers for brain and nervous system disorders fell 50% to 129 – but that last year, investors poured $3.3 billion into the field, more than in any of the last ten years. The raise for Denali is a series A, the very first round of getting funding for a new company. It is the largest such round in biotech history.

One reason for the overstuffed purse: One co-founder, Denali’s chairman of the board of directors, is Marc Tessier-Lavigne, a well-known neuroscientist and president of Rockefeller University in New York. He served as Genentech’s head of drug research during its legendary run in the late 2000s, before the company was bought by Roche in 2009. He’s also giving up a board seat at pharma giant Pfizer PFE +1.18% in order to make time for his new company.

“The science in the field has been breaking open and this has been accelerating over the past decade,” says Tessier-Lavigne. “Denali is based on the idea that the time is right to tackle these diseases systematically and deeply.”

Denali CEO Ryan Watts

Leading day-to-day operations as chief executive will be Ryan Watts, until now director of neuroscience at Roche’s Genentech division. Alex Schuth, who headed technology innovation and diagnostics business development at Genentech, is the third co-founder. The company will be based in San Francisco.

The company is named after the tallest mountain in North America. “For me it means an inspiring challenge,” says Watts. “We wanted a name that was recognizable that represents a huge unmet need.”To climb this particular mountain, Watts says that Denali will be avoiding already crowded areas in the development of drugs for diseases like Alzheimer’s. For instance, companies including Biogen, Eli Lilly , Merck, and Genentech are all trying to slow the progression of Alzheimer’s with drugs that block a substance called beta amyloid, which is present in tangles in the brains of Alzheimer’s patients. Watts says Denali won’t pile in.

Instead, Watts sees a new generation of drug targets emerging from human genetics. He says that just as oncogenes – cancer genes – have lead to a flood of cancer drugs, newly discovered genes linked to degenerative brain disease (the Denali guys called them degenogenes) will provide a basis for a new generation of brain medicines.

Denali co-founder Alex Schuth

Denali will also focus on how inflammation drives brain disease; how the trafficking of substances between cells is involved in Parkinson’s and Alzheimer’s; and on factors that influence how brain cells die that are common to all brain diseases. Already, the company is looking at least 12 different drug targets in these areas, though it will not disclose more about them yet.

Investors include Fidelity Biosciences, ARCH Venture Partners, Flagship Ventures and the Alaska Permanent Fund (represented by Crestline Investors). Additional investors include sovereign wealth funds, public mutual funds and private family offices, with significant reserves for additional future financing.

Robert Nelsen, co-founder of  ARCH Ventures and an investor in other hot biotech startups like JUNO Therapeutics and Agios, both of which now sport $4 billion market capitalizations, says that combining forces in a big effort is already drawing attention among researchers even before the company officially launches.

“The best scientists in the world are now calling us, “ Nelsen says. The next step, he says, is engaging the Food and Drug Administration about how to develop brain drugs more quickly, as has happened in HIV, hepatitis C, and cancer. “ You can’t wait 10 or 20 years for the perfect study in Alzheimer’s when it’s going to cost us a trillion dollars in today’s dollars by 2050. The societal cost of these diseases is mind-blowing.”

http://www.forbes.com/sites/matthewherper/2015/05/14/former-genentech-researchers-raise-217-million-for-company-to-fight-alzheimers-and-parkinsons/?ss=pharma-healthcareAlso on Forbes:

The Top 10 Biotech Companies In The U.S.

Tips for Optimizing PD Medications : By Dr. De Leon

MAY 14, 2015 ~ DEFEATPARKINSONS

One of the biggest reasons for hospitalizations in the Parkinson’s community aside from medical emergencies and trauma (usually because medications not well adjusted) in my experience is acute side effects such as hallucinations, confusion, psychosis, or pain all stemming from improper intake of prescribed Parkinson’s medications.

One way to avoid unnecessary ER visits is to be informed about the medications we have been prescribed by our neurologists/MDS physicians.

Keep a detail record of all medications prescribed. This should include dosing, frequency, and duration as well as prescribing physician. Plus you should leave a space for comments on side effects next to each medication. Also include in this chart any research trials and the name and number of coordinator. PDF (Parkinson’s Disease Foundation) as well as NPF (National Parkinson’s Foundation) have charts which you can down load or you can make your own.

First, each time you visit your physician take your entire pill bottles including both prescription and over the counter medications. Even esoteric things like over the counter laxatives can be of importance. These can lead to dehydration and electrolyte abnormalities causing leg cramps which can be confused with potentially similar side effects with some PD meds such as Neupro patch which can also cause cramps. Other medications can interfere with prescribed Parkinson’s medications (e.g. certain muscle relaxants are contraindicated with intake of Azilect) causing potentially dangerous reactions.

Second: if you have trouble understanding or communicating bring someone with you to every visit which can serve as an interpreter and help remember and jot down instructions for you.

Third, when you receive a new medication take time to understand what is for. Find out if it be replacing another one?  Will it be taken in conjunction with existing medications?  How do you start it? Do you have to tapper up? If replacing another one do you simply stop existing medication or do you have to wean off?  What is starting dose and target dose? Find out about potential side effects? What should you do if they occur? Find out if there are any dietary restrictions.

Fourth: are all medications in the class prescribed the same? Are there assistance programs if you can’t afford new medication prescribed? Are there similar medications if insurance won’t cover and no assistance programs? Get description of the plan.

Fifth, it is important that when you obtain your medications you maintain a regular schedule which is easy to do when things are going well but much more difficult when life starts throwing curve balls like unexpected sickness of a loved one causing you to travel outside of your comfort zone. I recommend getting a pill box to keep things organized. Always keep some extra (at least 2 weeks) in case of unexpected emergencies like in climate weather where you are forced to be shut in. Maintain an emergency medical kit ready at all times. You can get one from NPF. Don’t double medications if you missed a dose. If away from home and run out simply ask pharmacist to lend you some till you can contact your doctor. Remember, there are a number of gadgets and apps to remind you to take your medications on time. Do not self medicate. Sometimes unknowingly we may be making our symptoms worst. We feel bad so we take Sinemet or derivative thereof and then we feel worst when it runs out so we take more and we get in a vicious cycle. In cases of dyskenisias and PD symptom fluctuation sometimes LESS isMORE! The goal of treatment is to maintain as close a balance as we can to natural brain equilibrium as possible which means usually a cocktail treatment because our brain is run an in constant equilibrium between all the different neurotransmitters offsetting this delicate system  is what gets us into trouble when we replace only one type of chemical in my experience!

Talk to your physician always before making any changes or adjustments to your regimen.

Finally, keep in mind differences in brand vs. generic although they are not supposed to be much difference between the two because according to the FDA generics are supposed to have same active ingredient leading to similar quality and performance however because they are not required to have same inactive ingredient there may be great variability noticed from person to person when switched and even between varying generics in the same individual.  Always make sure to look at the prescription handed to you by pharmacist to make sure you are getting the right medication and dosage since pills may look very different month to month if getting generics leading to confusion and increase side effects especially if having dyskenisias; variation in medication maybe the greatest culprit. If having motor fluctuations stick to same generic or buy brand if possible. Teva makes the best quality generics.

December 5, 2014 | Foreword by Darcy Blake, article by Maria De Leon | Dr. De Leon has a remarkable story of tenacity and resilience. After attending school at Hahnemann University Hospital in Philadelphia, and working as a  fellow at Baylor College of Medicine with Dr. Jankovic, she studied at Queen Square Institute in London before she held a solo practice as a Movement Disorder Specialist for ten years. Her career as a physician stopped short when the unthinkable happened, and this is her remarkable story of overcoming obstacles to help people with Parkinson’s Disease. DB

sources:

http://www.pdf.org

http://www.npf.org

A tale of two roads into protein unfolding

May 13,2015

You are taking a class on origami and Mr. Otaki asks you to fold that little red piece of paper into a very elaborate design. You have to do it in a very short time. You try your best but you fail. Your origami sucks!

Bad protein folding is associated with a number of age-related diseases including Parkinson's, Alzheimer's, Huntington's and even cancer.
Credit: Guilherme Augusto

Surprised, Mr. Otaki wants to understand what you did wrong and starts unfolding your failed attempt at a red dragon. The unfolding reveals all the intermediate steps you went through and indicates exactly how you screwed up. That attempt at a red dragon is now history and lies in the trash basket. You get another square and prepare for a fresh attempt at mastering the art of paper folding.

Protein folding is the process by which a protein undergoes many folding steps until it assumes its functional conformation, a three-dimensional structure called the native state of the protein. It is in this native state that proteins are able to do the many jobs assigned to them, including cell division, growth, cell nutrition and locomotion, among others. The story of protein folding is not unrelated to origami--except that unlike bad paper folding, which simply goes in the trash, bad protein folding is associated with a number of age-related diseases including Parkinson's, Alzheimer's, Huntington's and even cancer.

It is already known that protein misfolding generates a number of intermediate proteins that may accumulate in the brain. For instance, an abnormally folded version of the protein amyloid beta accumulates in the brain of Alzheimer's patients, damaging neurons and impairing the brain in carrying out its normal functions. Thus, a good understanding of protein folding and misfolding might be crucial for the development of treatments against these devastating diseases.

Researchers have used physical and chemical strategies such as high pressure and urea to force folded proteins into unfolding so all the steps, and the intermediate proteins that are generated along the process, can be observed and studied. However, the mechanisms underlying the effects of these two strategies and how exactly they work in protein unfolding have never been clearly understood.

Using nuclear magnetic resonance spectroscopy, a technique that provides detailed information on the structure, composition, state, and chemical environment of molecules, and small-angle X-ray scattering, which informs on the shape and size of macromolecules, Dr. Jerson Lima Silva and Dr. Guilherme Augusto, at the Federal University of Rio de Janeiro, Brazil, have revealed for the first time all the mechanistic details on how high pressure and urea act on proteins. "We were surprised to see that these two strategies differ significantly in the way they force proteins into unfolding," says Dr. Silva.

In a paper entitled "A hypothesis to reconcile the physical and chemical unfolding of proteins" and published in the renowned journal Proceedings of the National Academy of Sciences in the week of May 11, 2015, the two authors show that whereas high pressure pushes water molecules towards the protein until it unfolds, urea has the opposite effect by pulling the protein's molecules. Although the final result seems similar, with the protein unfolding in both cases, the intermediates formed are very different and the roads to unfolding are very specific.

"The push-and-pull hypothesis predicts that the molecular mechanisms leading to protein unfolding can be very different depending on the nature of the causal agent involved," says Dr. Guilherme Augusto.

These new findings greatly contribute to our understanding on how proteins' native state might be disrupted, and hopefully will open effective new avenues for how to avoid such disruption. 

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/293765.php?tw

Amarantus Receives Notice of Allowance for U.S. Patent Application Covering Proprietary Methods of Administration and Compositions in the Treatment of Parkinson's Disease

Press Release | Wed May 13, 2015 1:00pm EDT

SAN FRANCISCO and GENEVA, Switzerland, May 13, 2015 (GLOBE NEWSWIRE) -- Amarantus BioScience Holdings, Inc. (OTCQB:AMBS), a biotechnology company focused on developing therapeutic and diagnostic products for neurological disorders and orphan indications, announced that a Notice of Allowance was received from the U.S. Patent and Trademark Office (USPTO) for U.S. Patent Application Serial No. 11/713,156 entitled, "Pharmacological Treatment of Parkinson's Disease." Upon issuance, the patent will provide additional intellectual property protection for the Company's lead product candidate, eltoprazine. The allowed patent claims cover methods and compositions for the administration of eltoprazine for the alleviation of akinesia, rigidity and/or tremor associated with Parkinson's disease.

Eltoprazine, a small molecule 5HT1A/1B partial agonist, is currently preparing to commence Phase 2b clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID). PD-LID is an abnormal involuntary, movement disorder resulting from prolonged levodopa-based therapy, the most commonly prescribed treatment for Parkinson's disease (PD). PD-LID occurs in approximately 60-80% of PD patients and is one of the most difficult problems facing people with the disease. This dyskinesia can be severely disabling and impact quality of life by prohibiting the ability to perform routine daily functions.

"This Notice of Allowance for eltoprazine in Parkinson's is a meaningful addition to the intellectual property estate we have established related to eltoprazine and comes at an important time as we are gearing up to commence enrollment and patient dosing in our Phase 2b program in PD-LID," said Gerald E. Commissiong, President & CEO of Amarantus. "We believe eltoprazine has tremendous potential as an important therapy to address a significant unmet need and improve the quality of life for individuals with Parkinson's disease and their families."

Amarantus expects to initiate patient enrollment and dosing in a 60-subject Phase 2b clinical study with eltoprazine in individuals with PD in the second quarter of 2015. The PD-LID study will be conducted at Parkinson's disease centers of excellence in the United States and Europe. This trial is a double-blind, placebo-controlled, four-way crossover, dose range finding, clinical study designed to evaluate dose response effect of repeated eltoprazine dosing on safety, tolerability and dyskinesia severity using state-of-the-art rating scales, diaries and motion sensors. Pharmacokinetics and pharmacodynamics will also be evaluated.

The USPTO issues a Notice of Allowance after it makes a determination that a patent should be granted from a patent application.

About Eltoprazine

Eltoprazine is a small molecule 5HT1A/1B partial agonist in clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID), adult attention deficit hyperactivity disorder (ADHD), and Alzheimer's aggression. Eltoprazine has been evaluated in over 680 human subjects to date, and has a well-established safety profile. Eltoprazine was originally developed by Solvay Pharmaceuticals, now AbbVie, for the treatment of aggression. Solvay out-licensed the eltoprazine program to PsychoGenics. PsychoGenics licensed eltoprazine to Amarantus following successful proof-of-concept trials in PD-LID and adult ADHD.

About Parkinson's Disease and Levodopa-Induced Dyskinesia (PD-LID)

Parkinson's disease is a chronic, progressive neurodegenerative disorder that causes motor symptoms such as tremors, rigidity and slowed movements as well as non-motor symptoms including cognitive impairment, mood disorders and autonomic dysfunction. The Parkinson's Disease Foundation estimates that there are approximately one million people living with Parkinson's disease in the United States and seven to 10 million PD patients worldwide. The most commonly prescribed treatments for Parkinson's disease are levodopa-based therapies. In the body, levodopa is converted to dopamine to replace the dopamine loss caused by the disease. As dopamine neurons in the brain are lost the therapeutic efficacy of levodopa attenuates, and increased use is associated with a side effect of dyskinesias. These are involuntary, uncontrollable and often exaggerated and jerky movements. They are distinct from the static, rhythmic tremor as a symptom of Parkinson's disease. Levodopa-induced dyskinesia can be severely disabling, rendering patients unable to perform routine daily tasks.

About Amarantus BioScience Holdings, Inc.

Amarantus BioScience Holdings (AMBS) is a biotechnology company developing treatments and diagnostics for diseases in the areas of neurology, psychiatry, ophthalmology and regenerative medicine. AMBS' Therapeutics division has development rights to eltoprazine, a Phase 2b ready small molecule indicated for Parkinson's disease levodopa-induced dyskinesia, adult ADHD and Alzheimer's aggression, and owns the intellectual property rights to a therapeutic protein known as mesencephalic-astrocyte-derived neurotrophic factor (MANF) and is developing MANF-based products as treatments for brain and ophthalmic disorders. AMBS' Diagnostics division owns the rights to MSPrecise®, a proprietary next-generation DNA sequencing (NGS) assay for the identification of patients with relapsing-remitting multiple sclerosis (RRMS) at first clinical presentation, has an exclusive worldwide license to the Lymphocyte Proliferation test (LymPro Test®) for Alzheimer's disease, which was developed by Prof. Thomas Arendt, Ph.D., from the University of Leipzig, and owns intellectual property for the diagnosis of Parkinson's disease (NuroPro). AMBS also owns the discovery of neurotrophic factors (PhenoGuard™) that led to MANF's discovery.

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Parkinson's Protein May Spur Immune Response

TUESDAY, May 12, 2015 (HealthDay News) 

Researchers say more work needs to be done to understand findings By Robert Preidt

-- A protein known to accumulate in Parkinson's disease and other degenerative brain disorders activates the brain's immune defenses, researchers say.
The protein is called a-synuclein. The researchers noted that diseases such as Parkinson's and Lewy body dementia are characterized by the abnormal accumulation of this protein. The immune response appears to increase inflammation.
The researchers said the high blood pressure drug candesartan and an experimental drug both reduce the immune response triggered by the protein. But much more research is needed on these findings.
"We have made important progress in understanding how a-synuclein sets up the chronic brain inflammation that is a hallmark of these diseases," study senior author Kathleen Maguire-Zeiss, an associate professor in the department of neuroscience at Georgetown University Medical Center in Washington, D.C., said in a university news release.
The normal role of a-synuclein is unclear, but it is known that the protein can quickly change its structural shape -- "misfold" -- and become toxic. Misfolded a-synuclein can activate cells that provide the main immune defense in the central nervous system.
"The real job of [these immune cells] is to keep the brain healthy by getting rid of pathogens as well as cellular debris," Maguire-Zeiss said. "However, in a diseased state [these immune cells] can become chronically activated, leading to a continuous onslaught of inflammation which is damaging to the brain."
The study was published online May 12 in the journal Science Signaling.
More information
The U.S. National Institute of Neurological Disorders and Stroke has more about Parkinson's disease.
SOURCE: Georgetown University Medical Center, news release, May 12, 2015
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