Positive Phase 2a Results for Continuous, Noninvasive, Intraoral Levodopa-Carbidopa Administration to Treat Parkinson's Disease

Published: Oct 8, 2015 7:23 a.m. ET

PRESS RELEASE

SynAgile Corporation

- Continuous intraoral administration of levodopa-carbidopa reduced variability in plasma levodopa concentrations and reduced OFF time associated with Parkinson's disease- Met primary endpoint with statistically significant reduction in levodopa plasma variability versus standard intermittent oral tablet therapy- Met secondary endpoints with statistically significant reduction in OFF time and with improvement in UPDRS III motor score versus standard intermittent oral tablet therapy- No clinically significant adverse events- No observed delivery-site reactions

WILSON, Wyo., Oct. 8, 2015 /PRNewswire/ -- SynAgile Corporation (www.SynAgile.com), a privately held pharmaceutical company that develops and commercializes drug delivery systems using its proprietary OraFuse™ intraoral technology platform, today announced positive results from a proof-of-concept, Phase 2a, open-label clinical trial of continuous intraoral administration of levodopa-carbidopa (LD/CD).

"We are extremely pleased that the primary and secondary endpoints in our Phase 2a trial were met, demonstrating that continuous intraoral delivery of LD/CD provides reduced variability in plasma levodopa concentrations and a significant reduction in motor complications. OFF time was reduced by 43% compared to standard oral LD/CD tablet therapy," said Ephraim Heller, CEO of SynAgile. "SynAgile is developing its DopaFuse™ product as a continuous, noninvasive LD/CD therapy to address the problem of levodopa-induced motor complications, a large, unmet need facing Parkinson's patients today. These results were achieved with a noninvasive therapy that requires no surgery, bulky pumps, or needles. Continuous intraoral LD/CD therapy will appeal to many patients whose motor complications are not adequately controlled with standard oral medications. Furthermore, DopaFuse™ will potentially avoid the side effects and human factor problems associated with deep brain stimulation and Duodopa™ therapy."

Motor complications include OFF time and dyskinesia associated with chronic levodopa treatment. Motor complications affect most patients with advanced Parkinson's disease and are considered to be one of the most important issues facing Parkinson's disease patients today.

"Motor complications, and specifically OFF time, can have a profoundly negative impact on the lives of Parkinson's disease patients. A safe, convenient, noninvasive, nonsurgical, oral levodopa therapy would be a major advance in treatment," said Prof. Warren Olanow, co-Principal Investigator of the study, Chairman Emeritus, Department of Neurology, Mount Sinai School of Medicine, CEO of Clintrex LLC, and a member of the SynAgile Scientific Advisory Board. "The reduction in OFF time was clinically significant, and there were no treatment-related adverse events. The results suggest that continuous intraoral LD/CD administration may provide a safe, noninvasive approach for controlling OFF time," said Prof. Olanow.

The study compared continuous intraoral administration of LD/CD versus standard intermittent LD/CD tablets taken 4–8 times daily in patients with advanced Parkinson's disease. Continuous administration was defined as administration of a dose of LD/CD suspension every 5–10 minutes. Each patient served as his/her own control (described below). For the primary endpoint, statistically significant improvements were observed for variability in plasma levodopa concentration (as determined by linearity) and for reduction in 1-hour and 2-hour fluctuation indexes (p < 0.001 for each). OFF time was reduced by 43% (p < 0.001), and the UPDRS Part III motor score improved (p = 0.010).

Trial Design

The Phase 2a trial was an open-label, single-center study of 18 Parkinson's disease patients who experienced ≥2 hours of OFF time per day. Profs. Warren Olanow and Fabrizzio Stocchi served as Co-Principal Investigators. Standard intermittent oral LC/CD tablets were compared with the same total doses of LD/CD suspension delivered into the mouth every 5–10 minutes. The study was conducted at Hospital San Raffaele in Rome, Italy. Patients were admitted to the clinic on Day 1 for baseline evaluations. On Day 2 (the "Control Day"), LD/CD was administered as commercially available LD/CD tablets at each patient's pre-baseline dosing regimen. Plasma levels of levodopa as well as ON and OFF time were measured repeatedly over the course of 8 hours. On Day 3 (the "PK Day"), a suspension of LD/CD was administered intraorally every 5–10 minutes over a period of 8 hours at a dose equal to the total dose of standard oral LD/CD that the patient consumed over the same 8-hour period on the Control Day, and plasma levels of levodopa were obtained. On Day 4 (the "Efficacy Day"), each patient received his or her first LD/CD morning dose as an oral tablet at the same dosage as the first morning dose on the Control Day. They then received the balance of the total 8-hour dose that they took on the Control Day by way of intraoral administration of a suspension of LD/CD every 5–10 minutes over a period of 8 hours. ON and OFF time were assessed as on Day 2. Patients were then discharged from the clinic on their standard medication and returned on Day 18 for a safety evaluation.

The primary endpoint was defined as the variability of the levodopa concentrations; we compared standard intermittent oral and continuous intraoral administration. Pharmacokinetic endpoints included deviation from linearity and the mean levodopa fluctuation index (Cmax^’Cmin)/Caverage). Efficacy was measured by neurologist-based assessment of motor state and dyskinesia at 30-minute intervals over the 8 hours and by UPDRS Part III, assessed at 0, 2, 4, and 8 hours on the Control Day (Day 2) and the Efficacy Day (Day 4).

Safety parameters measured included physical examinations, neurological examinations, ECGs, vital signs, blood and urine laboratory assessments, and oral site assessments by both the neurologist and the patient.

Full results of the study will be presented at an upcoming scientific meeting.

About OraFuse™ and DopaFuse™

SynAgile is developing the OraFuse™ drug delivery platform for the continuous oral delivery of drugs with poor pharmacokinetics. OraFuse™ consists of a miniature, disposable, drug-delivery device carried on a small, tooth-attached retainer that continuously infuses medication into the mouth. SynAgile's first product is DopaFuse™, which uses the OraFuse™ device to infuse a proprietary formulation of LD/CD into the mouth for the treatment of Parkinson's disease. DopaFuse™ is being developed for daily use by Parkinson's disease patients. The LD/CD is swallowed with the patient's saliva and absorbed via the conventional gastrointestinal route. The DopaFuse™ drug formulation has no taste, and the infusion is imperceptible to the patient. The DopaFuse™ system is not visible to others, is comfortable to wear, and does not interfere with speech, swallowing, or drinking. DopaFuse™ is intended to enable patients with Parkinson's disease to achieve more-constant plasma levodopa levels and reduce their motor complications. DopaFuse™ will provide patients with a safe, convenient, noninvasive therapy to reduce motor complications. In contrast to other continuous levodopa delivery systems, DopaFuse™ requires no surgical procedures or needles.

Levodopa is widely recognized as the most efficacious treatment for Parkinson's disease symptoms. However, levodopa is quickly broken down in the body and its absorption is unpredictable. Even when taken 4–8 times per day, standard oral levodopa tablets often produce widely varying plasma levodopa concentrations over the course of the day. Low plasma levodopa concentrations typically result in OFF time, characterized by tremor, rigidity, slowness of movement, and postural instability. High plasma levodopa concentrations often result in dyskinesia, characterized by involuntary muscle movements. Patients with advanced Parkinson's disease can spend many hours each day in the OFF state or with dyskinesia.

About Parkinson's Disease

Over one million people in the US and over seven million people worldwide suffer from Parkinson's disease, a neurodegenerative disorder caused by the diminished production of dopamine, which results in progressive impairment of motor function, including tremors at rest, rigidity, and impaired movement. Even when treated with the current standard of care, the majority of patients with advanced Parkinson's disease continue to experience motor complications (OFF periods and dyskinesia). These motor complications reduce patients' ability to lead productive, independent lives and are recognized by patients, caregivers, and healthcare professionals as one of the most troubling and debilitating issues associated with the disease.

About SynAgile

SynAgile is a biopharmaceutical company focused on developing and commercializing transformative therapeutics using its proprietary OraFuse™ intraoral continuous dosing technology, with an initial focus on treating debilitating motor complications in patients with Parkinson's disease using its DopaFuse™ levodopa-carbidopa therapy.

OraFuse and DopaFuse are trademarks of SynAgile Corporation. Duodopa is a trademark of AbbVie Inc.

Contact

SynAgile Corporation

Ephraim Heller, CEO

(510) 788-4435

eheller@synagile.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/synagile-corporation-announces-positive-phase-2a-results-for-continuous-noninvasive-intraoral-levodopa-carbidopa-administration-to-treat-parkinsons-disease-300156341.html

http://health.einnews.com/article/290510978/FGCvnzxbrordt8Z-

Boxing exercise program to fight Parkinson's comes to Augusta

By Tom Corwin

Staff Writer

Wednesday, Oct. 7, 2015

Still smarting from a diagnosis of Parkinson’s disease in August, Jim Bodden of Evans hopes to soon fight back – actually punch back – against his disease.

Back |  Next 

TODD BENNETT/STAFF

Certified trainer Tambra Craven is bringing the Rock Steady Boxing program to the Augusta area. The boxing-like exercises can help patients with Parkinson's disease. 

Most people would associate Parkinson’s and boxing with one of its most famous patients, boxing great Muhammad Ali. But the Rock Steady Boxing program, which began in Indianapolis and has spread across the country, finds boxing-based exercises can provide a number of benefits to patients, said Tambra Cra­ven, a certified trainer who began Day One Fitness and became certified in Rock Steady Boxing to start an affiliated program in Augusta.

Boxing exercises are one of the highest-rated ways of keeping fit and can help push people beyond what other exercise regimens demand, she said.

“If you got on a treadmill and worked at your own pace you wouldn’t see the same benefits,” Craven said. But there are also aspects to it that specifically address issues Parkinson’s patients have, she said.

“It’s a full-body workout. There are a lot of core and stability exercises in boxing,” Craven said. “Of course that helps people who have issues with stability, gait problems, things like that.”

The program also incorporates other aspects, such as getting the participant to yell while punching or yell back during drills because Parkinson’s patients can lose their voices over time. Bod­den said he is already dealing with that and is in speech therapy.

“That is one of the important areas that you lose,” he said, his voice already straining. “You have to work hard to keep it.”

The classes will also help patients deal with some of the realities of their disease, such as falling, Craven said.

“We practice falling,” she said. “We’re going to fall. It’s going to happen. Get comfortable with how you fall, how to safely fall and not injure yourself or minimize injury, and then get back up and not be embarrassed about it.”

There is one key reason the Rock Steady Boxing program is succeeding and spreading: People like it, Craven said.

“It’s fun,” she said. “So when you are talking about people who may not feel the best, they want to come do something that is fun. It is more fun than physical therapy. It’s also way cooler to say.”

Classes will start Nov. 2, with a location to be determined. Though the program normally splits participants into four levels based on ability, the first ones are likely to be mixed with modifications for those who need them. 

The hope – and the reason the group is called Day One Fitness – is that from the first day of diagnosis patients will hear about the program and what it might offer, Craven said.

“There’s a gym around the corner that can help bring hope into your lives, that will help slow down the progression of this disease,” she said.

http://health.einnews.com/article/290333562/VvScdcAI3OYwYZTk

The Parkinson Alliance Survey Reports a Relationship Between Patience and Well-Being in Parkinson's Disease

KINGSTON, N.J., Oct. 7, 2015 /PRNewswire-USNewswire/ -- 

The Parkinson Alliance conducted its 19th survey-based research, entitled Patience and Well-Being in Parkinson's Disease. The survey examined how patience relates to functional impairment and psychological well-being in Parkinson's disease (PD).  Data was gathered from 1,482 participants with Parkinson's and included individuals who have had Deep Brain Stimulation (DBS) and those without DBS.  This survey revealed that in individuals with Parkinson's disease (with and without DBS), patience was significantly related to psychological well-being and quality of life.  While patience did not have a strong relationship with the level of functional difficulty the person with Parkinson's experiences, functional difficulty did have an impact on psychological well-being and quality of life.

In the study, the majority of individuals reported that patience helps them cope with their symptoms, and over half of the participants reported that patience increased their engagement in social activities.  Results from our survey supports the notion that patience can be a buffer against negative emotions in stressful situations, allow the person to cope more adaptively with frustrations, facilitate positive interpersonal interactions, and facilitate goal attainment.  Exercise was the number one technique that survey participants used to increase their patience.

"There are numerous adaptive coping mechanisms that may relate to increasing patience that are unknown, unfamiliar or underutilized by individuals with PD.  Furthermore, a more holistic approach to well-being to address a broader scope of wellness for people with PD and family and/or carers is being proposed.  Three facets of the 'well-being model' rather than the 'symptom-focused model' include mindfulness (of which "patience" is a part), perspective management, and behavioral activation," comments Jeffrey Wertheimer, Ph.D., ABPP-CN, clinical neuropsychologist and Chief Research Consultant for The Parkinson Alliance.  

Information about patience and additional aspects of psychological well-being as it relates to individuals with PD are discussed in this report.  The entire report is available for download at www.dbs4pd.org and includes take home points, general implications, and recommendations.

About The Parkinson Alliance

The Parkinson Alliance is a national non-profit organization dedicated to raising funds for Parkinson's research and improving the quality of life in the DBS community.  After undergoing bi-lateral DBS in 2000, Margaret Tuchman, President of PA, founded DBS4PD.org to keep the community informed.

Contact

Carol Walton

CEO

The Parkinson Alliance

1-800-579-8440

info@parkinsonalliance.org

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/the-parkinson-alliance-survey-reports-a-relationship-between-patience-and-well-being-in-parkinsons-disease-300155779.html

Motor Problems Not First Effect of Parkinson's

Oct. 3,2015

MONTREAL -- The nonmotor manifestations of Parkinson's disease -- including GI and urinary problems, cognitive decline, sleep difficulty, and pain -- pose a substantial burden to patients, often being prominent before the motor problems develop, a researcher said here.

In a retrospective audit of 517 patients, 23% were graded as having a severe nonmotor symptom burden even as the Hoehn-Yahr scale of motor decline was moderate, at a median score of 2.4, reported Elisaveta Sokolov, MBBS, of King's College in London.

Moreover, the nonmotor symptom burden was very severe in 21% of patients, yet their Hoehn-Yahr scale score was a median of 2.9, which is not considered advanced from a motor perspective, Sokolov said at the World Parkinson Congress here.

"These observations suggest that even at relatively mild motor stages, the nonmotor symptom burden can be great and can have a huge impact on patients' quality of life," she said.

"Parkinson's disease is no longer considered a complex motor disorder characterized by extrapyramidal symptoms, but a progressive multisystem or multiorgan disease with variegated neurologic and nonmotor deficiencies," she explained.

Her research team has been focusing on the nonmotor aspects of Parkinson's disease not only because of their quality of life impact, but also because this can help elucidate the etiology of the disease and identify potential targets for disease-modifying drug therapies.

Patients often report that nonmotor manifestations are more disabling and less amenable to treatment than some motor symptoms.

The current study was part of a 5-year longitudinal, naturalistic study of nonmotor symptoms and progression in early and late disease; researchers also evaluated the relationship between nonmotor manifestations and motor decline.

Patients in this analysis were predominantly men, whose mean age was 68 and whose mean Hoehn-Yahr stage was 2, which reflects bilateral involvement without impairment of balance.

The scale used in this study ranged from grades 1 to 5, with grade 1 representing minimal functional disability and 5 being confinement to a wheelchair or bed. Among the 517 patients in this cohort, only 1% were classified as having grade 1, or mild, nonmotor symptoms, 30% were grade 2, or moderate, and 69% were grades 3/4, representing severe and very severe involvement.

Among those with the grade 3/4 nonmotor symptoms, some patients had specific dominant endophenotypes, featuring primarily sleep or fatigue problems.

Only a single patient had no nonmotor symptoms at all, Sokolov noted.

As with motor manifestations, many of the nonmotor symptoms are associated with Parkinson's disease itself."However, recent evidence suggests that nonmotor symptoms such as anxiety, tingling, coldness of limbs, and unclear thinking may frequently occur before motor symptoms emerge, highlighting the importance of their recognition in clinical practice," she noted.

This study emphasizes the importance of including assessments of nonmotor function in patients with Parkinson's disease with the goal of implementing true holistic care of the multi-morbid patient with the disease, she concluded.

The study was funded by the U.K. National Institute of Health Research.

http://www.medpagetoday.com/MeetingCoverage/WPC/42039

What is impulsive and compulsive behaviour?

POSTED BY: ADMIN | OCTOBER 5, 2015

Peter Raymond

Impulsive and compulsive behaviour is a possible side effect of some Parkinson’s drugs. Although only a relatively small number of people experience this behaviour, it can have a significant impact on the person affected and those around them.

Impulsive and compulsive behaviour can affect some people who take dopamine agonists, but can also affect people who take other Parkinson’s drugs, in particular levodopa.

If you’re prescribed medication for Parkinson’s, it’s important that you and your specialist or Parkinson’s nurse discuss the potential risk of impulsive and compulsive behaviour.

Our Impulsive and compulsive behaviour in Parkinson’s monitoring and information tool can help with this.

This can also be used to monitor treatment over time.

Watch our film below and find out what you can do if you’re affected by impulsive and compulsive behaviour:

Transcript

What is impulsive and compulsive behaviour?

Impulsive behaviour is when a person can’t resist the temptation to carry out certain activities.

These are often activities that give an immediate reward, such as shopping or gambling.

Compulsive behaviour is when a person has an overwhelming drive or urge to act in a certain way, often repetitively, to reduce the worry or tension that they get from their urge.

Some people continue to act in this way, even if they no longer get any pleasure or reward.

In many cases, this behaviour is out of character and the person may carry out these activities without any thoughts about financial, social or legal consequences.

We have a dedicated impulsive and compulsive behaviour section on our online forum for people to share their experiences and get support.

Impulsive and compulsive behaviour is also referred to sometimes as impulse control disorder or ICD.

Types of impulsive and compulsive behaviour

This behaviour can be expressed in one or more of these ways:

• addictive gambling
• obsessive shopping – a preoccupation with buying things
• binge eating
• hypersexuality – a focus on sexual feelings and thoughts

Punding, or compulsive hobbyism, is when someone does things such as collecting, sorting or continually handling objects. It may also be experienced as:

• a deep fascination with taking technical equipment apart without always knowing how to put it back together again
• hoarding things
• pointless driving or walking
• talking in long monologues without any real content

Addiction to Parkinson’s medication, called dopamine dysregulation syndrome, is when a person takes more of a drug than is needed to control their Parkinson’s symptoms.

Are certain people more likely to experience impulsive and compulsive behaviour?

You are more likely to experience impulsive and compulsive behaviour if you’re:

• diagnosed with Parkinson’s at a young age
• male
• single and live alone
• a smoker
• someone with a personal or family history of addictive behaviour

If you’re aware that you, or a friend or relative, may be experiencing impulsive and compulsive behaviour, don’t live in denial. I don’t want anyone else to go through what I’ve been through.

If you have a history of ‘risk-taking’, such as gambling, drug abuse or alcoholism, you may be more likely to develop dopamine addiction.

This is where you take more of your medication than is needed to control your Parkinson’s symptoms (known as dopamine dysregulation syndrome).

It’s important to remember that not everyone will experience this side effect, so it shouldn’t put you off taking your medication.

You should work with your specialist or Parkinson’s nurse to find the most appropriate treatment option for you, and you should monitor the effects of this treatment together.

Spotting the signs of impulsive and compulsive behaviour

Impulsive and compulsive behaviour is not normal.

If you think you or another person with Parkinson’s may be experiencing impulsive and compulsive behaviour, tell your GP, specialist or Parkinson’s nurse right away, so they can help.

Someone experiencing impulsive or compulsive behaviour may not realise they have a problem. So it’s important that carers and family members note any unusual behaviour and tell the appropriate healthcare professional as soon as possible.

Some of this behaviour may be embarrassing and you may feel uncomfortable talking to a healthcare professional about it. But remember that they will have spoken to others with similar problems before.

You can use our Impulsive and compulsive behaviour in Parkinson’s monitoring and information tool to help with this discussion.

Treatment for impulsive and compulsive behaviour

Impulsive and compulsive behaviour can be controlled. Treatment may involve reducing the daily dose of Parkinson’s medication, having psychotherapy and looking into other types of Parkinson’s medication.

We do not advise anyone to stop taking or to change their Parkinson’s drugs without seeking the advice of their health professional.

Dopamine agonist withdrawal syndrome can happen if someone stops taking dopamine agonists suddenly. This can lead to symptoms such as depression, anxiety and pain.

You’ll find more detail in our Impulsive and compulsive behaviour in Parkinson’s information sheet.

Legal action against drug manufacturers

If you’re thinking about taking legal action against a drug manufacturer, there may be a limited time frame in which to do so.

Anyone considering this path would need to seek specialist legal advice as soon as possible.

Impulsive and compulsive behaviour research

We’ve published the results of 2 research projects we funded on impulsive and compulsive behaviour. These projects focused on risk factors and how the symptoms should be managed.

http://healthpassion.info/parkinsons-drugs-and-impulsive-and-compulsive-behaviour/

AMARANTUS ANNOUNCES PUBLICATION OF STUDY ON TARGETED DELIVERY OF MANF TO BRAIN AREAS ASSOCIATED WITH PARKINSON'S DISEASE

- Renishaw plc’s convection-enhanced delivery device results in accurate targeting and distribution of MANF to Parkinson’s disease-associated brain areas -

- Study confirms the potential of convection-enhanced delivery of MANF as a novel treatment strategy for Parkinson’s disease -

- Results support the co-infusion of gadolinium as a proxy measure of MANF distribution in future clinical studies -

SAN FRANCISCO and GENEVA, Oct. 06, 2015 (GLOBE NEWSWIRE) --  

Amarantus Bioscience Holdings, Inc. (OTCQX:AMBS), a biotechnology company developing therapeutic and diagnostic product candidates in orphan indications and neurology, announced the publication of a study demonstrating the targeted delivery of mesencephalic-astrocyte-derived neurotrophic factor (MANF) to brain regions associated with Parkinson’s disease in a porcine model. The paper entitled, “Convection-enhanced delivery of MANF – volume of distribution analysis in porcine putamen and substantia nigra1,” from the collaboration with Renishaw plc's (LON:RSW) Neurological Applications Department and the Functional Neurosurgery Research Group at the University of Bristol, was published in the Journal of the Neurological Sciences.

The publication reports for the first time the distribution of MANF in putamen and substantia nigra following convection-enhanced delivery (CED) in a large animal model and confirms the potential of targeted infusion of MANF as a novel treatment strategy for PD. The study demonstrates that: (i) MANF can successfully be delivered to the porcine putamen and substantia nigra, the brain areas centrally involved in PD, and (ii) that pharmacologically meaningful volumes of distribution of MANF can be achieved using Renishaw's convection-enhanced delivery device currently in human clinical development.

“Our decades-long human experience with convection-enhanced delivery of protein therapeutics taught us that the therapeutic potential of neurotrophic factor treatment of PD is heavily dependent on the ability to accurately and effectively target the affected brain regions,” said Prof. Steven Gill, MB, FRCS, MS, honorary professor of neurosurgery at the University of Bristol. “These published data confirm the translational potential of CED of MANF as a novel treatment strategy in PD.”

“We now have definitive confirmation that MANF can be precisely and accurately delivered to specific sites in the brain that are affected by Parkinson’s disease. Moreover, MANF can be distributed via CED in a volume thought to elicit a therapeutic effect,” said Gerald E. Commission, President & CEO of Amarantus. “The availability of an accurate and effective targeting method to deliver MANF to the brain is an important step for the development of MANF in PD. We believe these data provide a firm basis for studies in non-human primates as well as subsequent human clinical trials.”

Study Summary
The porcine model is increasingly being used in neuroscience research as the large brain volume and similarity of cortical and subcortical anatomy to the human brain may offer increased translational relevance over rat and non-human primate models. The aims of this recently published study using convection enhanced delivery (CED) in pig brains were two-fold: (1) To assess the targeting and to determine distribution volumes of MANF in porcine putamen and substantia nigra and (2) to correlate the distribution volumes of MANF with co-infused gadolinium-DTPA.

Using a recessed-step catheter design it was possible to achieve reflux-free infusions in both putamen and substantia nigra. The volumes of distribution of gadolinium-DTPA and MANF were determined by real-time magnetic resonance imaging (MRI) and immunohistochemical analysis, respectively. The authors concluded that the distributions of gadolinium-DTPA and MANF correlated well and that co-infusion of gadolinium as a proxy measure of MANF distribution in future clinical studies is supported by these data.

CED of MANF resulted in an effective distribution within the target regions of the brain as evidenced by immunohistochemical staining. Comparison of the MANF diffusion (Vd) and infusion (Vi) volumes indicated an approximate (Vd:Vi) ratio of 3 in the putamen and 2 in the substantia nigra. The volume of the substantia nigra pars compacta (SNpc) in patients with PD has recently been reported as less than 120 mm3. An extrapolation of the results from this present study indicates that with a single catheter targeted to the human SNpc and assuming a Vd:Vi ratio of 2, it may be possible to distribute MANF throughout this target in approximately 30 minutes using a maximum infusion flow rate of 5 ml/min. Similar considerations apply to the delivery of MANF to the human putamen. Infusion times in the range of 30 to 120 minutes are likely to be acceptable to patients and reports are emerging of using faster flow rates safely in the human putamen which would further reduce the infusion time. Moreover, pre-clinical data from a rat PD disease model suggests that only a fraction of the striatal volume needs to be targeted to elicit a pharmacological effect.

The abstract, “Convection-enhanced delivery of MANF – volume of distribution analysis in porcine putamen and substantia nigra,” may be accessed online via the Journal of the Neurological Sciences at http://www.jns-journal.com/article/S0022-510X(15)00477-3/abstract.

1N.U. Barua, A.S. Bienemann, M. Woolley, M.J. Wyatt, D. Johnson, O. Lewis, C. Irving, G. Pritchard, S.Gill, Convection-enhanced delivery of MANF – volume of distribution analysis in porcine putamen and substantia nigra, Journal of the Neurological Sciences (2015), doi: 10.1016/j.jns.2015.08.003.

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 (programmed 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 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 (OTCQX:AMBS) is a biotechnology company developing treatments and diagnostics for diseases in the areas of neurology and orphan diseases. The Company has an exclusive worldwide license to intellectual property rights associated to Engineered Skin Substitute (ESS), an orphan drug designated autologous full thickness skin replacement product in development for the treatment of adult severe burns currently preparing to enter Phase 2 clinical studies. The Company is currently evaluating human clinical data from previously conducted studies in pediatric severe burns and Congenital Giant Hairy Nevus to support clinical development expansion into those areas.  AMBS also has development rights to eltoprazine, a small molecule currently in a Phase 2b clinical program for Parkinson's disease levodopa-induced dyskinesia with the potential to expand into adult ADHD and Alzheimer's aggression. AMBS owns the intellectual property rights to a therapeutic protein known as mesencephalic-astrocyte-derived neurotrophic factor (MANF) and is developing MANF as a treatment for orphan ophthalmic disorders, initially in retinitis pigmentosa (RP) and retinal artery occlusion (RAO). AMBS also owns the discovery of neurotrophic factors (PhenoGuard™) that led to MANF's discovery.

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).

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

http://health.einnews.com/pr_news/290110011/amarantus-announces-publication-of-study-on-targeted-delivery-of-manf-to-brain-areas-associated-with-parkinson-s-disease?n=2&code=lAb0qDE0aV13cmUw