Vaccine for Parkinson’s Disease Enters Phase 1 Clinical Trial
Copied from The Northwest Parkinson’s Foundation Weekly News Update
Brain Blogger - The word “vaccination” generally brings to mind the prevention of infectious disease. However, significant advances have recently been made in the field of therapeutic vaccination for the treatment of chronic human disorders including neurological conditions and cancer.
Simply put, a vaccine is a mixture of compounds (most often proteins) that are selected for their ability to activate the immune system. These compounds, also known as antigens, are then injected into the body where they prepare the immune system for a future assault. The result of such prophylactic vaccination is either complete immunity to the illness, or at least a significant reduction in disease severity.
While a prophylactic vaccine is administered as a preventative measure, therapeutic vaccines are intended to help fight a disease that has already taken root. For example, a therapeutic vaccine might be given to a patient with cancer in order to enlist the patient’s own immune system in the fight against the disease.
The problem with this kind of approach is ensuring that the antigen used in the vaccine does not induce an immune response against healthy parts of the body. Again, using cancer as an example, diseased cells often contain mutated proteins, or proteins that are not usually expressed in adult tissue (known as onco-fetal genes). This means that vaccines using these antigens specifically target cancer cells.
Recently, a therapeutic vaccine for Parkinson’s disease developed by Austrian pharmaceutical company Affiris entered a clinical trial, a landmark move in the management of a disease that is currently only treated at a symptomatic level.
Patients with Parkinson’s disease suffer from a number of debilitating symptoms that are the result of the loss of a particular class of neurons in the brain. These neurons are involved in the control of muscle function and are particularly sensitive to the neurotransmitter dopamine. It is for this reason that current treatments revolve around modulation of the levels of this chemical.
The underlying molecular cause of the disease is a protein called alpha-synuclein. Ordinarily this protein is found throughout the neocortex, hippocampus, thalamus, substantia nigra, and cerebellum, although its precise function remains unknown. Importantly, this protein is very unusual in that it does not fold up like the majority of proteins. Its “floppy”, unfolded appearance means that it is particularly susceptible to getting tangled up and forming protein aggregates within brain cells, thus sentencing the affected cell to death. The formation of protein aggregates also underlies other brain disorders, including Alzheimer’s disease and Creutzfeld-Jacob disease.
It is the alpha-synuclein protein tangles that are targeted by the vaccine currently in trials, PD01A. The study, funded by the Michael J. Fox Foundation to the tune of $1.5 million, will assess the safety of the vaccine in both men and women with Parkinson’s disease, with the results expected in July of 2014.
Given the prevalence of protein aggregates in brain diseases, therapeutic vaccination might therefore represent a promising future treatment for several neurological conditions.
Pig cell treatment for Parkinson's cleared for trial
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radionxz.co.nz - A new treatment that injects cells from a pig's brain into the brains of people with Parkinson's disease is one step closer to being used.
New Zealand company Living Cell Technologies has been given clearance from the Ministry of Healthy to trial the treatment called NTCELL.
In a world first, the brain cells of a piglet bred in Southland could soon be transplanted into people suffering from the disease.
The neurodegenerative condition stems from a lack of a chemical in the brain, dopamine, which causes a loss of coordination and uncontrolled movements.
The principal investigator for the trial, Barry Snow, says the pig cells keep nerves healthy and stop tremors.
"What we anticipate these growth factors will do from the pig cells is help the dying back nerve cells from Parkinson's disease start to regrow again. In fact, we know these cells from the pigs work really well in animal models."
Living Cell Technologies has tested the transplant on rats and monkeys and says both species had fewer tremors and better control of their movements.
A professor at the company, Bob Elliot, says they plan to test the transplant on four people with severe Parkinson's. He says if successful, it will be a better option compared with deep brain stimulation used now which uses electric currents to probe the brain.
"The electrical treatment doesn't do anything about regenerating the damaged part of the brain, it just stirs the brain up in that sort of general area. Whereas this treatment is actually getting right at where the cause of the problem is and replacing those dead brain cells with new ones."
Parkinson's New Zealand chief executive Deidre O'Sullivan says their members are excited and fully supportive.
"People always talk about a cure, however, slowing down progression or preventing progression is almost as good as a cure. In terms of impact on quality of life of people living with Parkinson's, it will have a massive impact."
But Ms O'Sullivan says they will remain cautious, as with any new treatment.
The Anti-Vivisection Society, which opposes experiments on animals, says that caution is warranted. Director Phil Clayton says humans do not react to treatments in the same way as animals.
"Experiments on other species like that don't give predictive results of what would happen in humans - so if that's all that's been relied on, they should stop and think again and find some either better evidence or not do the trials."
The trial will have to be assessed and approved by a health ethics committee before it can go ahead.
Living Cell Technologies' chief executive Andrea Grant says a similar trial that involved transplanting cells from a pig's pancreas into people with Type 1 diabetes was approved in New Zealand in 2008. A fourth trial is about to be held in Argentina.
Ms Grant says they will do what it takes to ensure that this trial is approved also.
"We've taken this technology platform now into appoximately 35 patients around the world and there's been no issue with viral or microbiological transfer in any of those patients.
"So in terms of the safety aspects - which is what ethics is mainly concerned with - we're feeling that we've ticked all the boxes."
Ms Grant says the company hopes to have its application approved by the end of this year so it can begin in 2013.
If all goes to plan, the NTCELL treatment could be available to the public in 2016.
Copyright © 2012, Radio New Zealand
Five abstracts evaluating Abbott's LCIG presented at Parkinson's disease congress
Copied from The Northwest Parkinson’s Foundation Weekly Newsletter
News Medical - Today Abbott (NYSE: ABT) announced results from five abstracts evaluating levodopa-carbidopa intestinal gel (LCIG), its investigational compound for advanced Parkinson's disease. The abstracts include the results from the second interim analysis of a long-term safety and tolerability trial, as well as secondary endpoint analyses from the Phase 3 pivotal trial. All of the abstracts were presented at The 16th International Congress of Parkinson's Disease and Movement Disorders, June 17-21 in Dublin, Ireland.
LCIG is currently approved in 40 countries. In the U.S., LCIG is an investigational therapy that is currently being evaluated in patients with advanced Parkinson's disease in additional Phase 3 clinical trials. In these trials, levodopa-carbidopa is administered in gel form, directly into the small intestine via a procedurally-implanted tube connected to a portable pump that delivers continuous supply of LCIG during awake hours.
Long-Term Safety and Tolerability
In a 54 week open-label safety and tolerability study of 354 patients with advanced Parkinson's disease, the primary endpoint of safety showed adverse events (AEs) were mostly mild to moderate, were generally associated with the Percutaneous Endoscopic Gastrostomy (PEG) tube placement procedure and its complications, were transient, and resolved over time.
In the secondary endpoint analysis from the open-label study, patients experienced an average daily "off" time of 6.7 hours, and 7.7 hours of "on" time without troublesome dyskinesia at baseline. "Off" time refers to periods of poor mobility, slowness and stiffness experienced by patients with Parkinson's disease, while "on" time refers to periods of good motor symptom control. At week 54, mean daily "off" time had decreased an average of 4.5 hours, and "on" time without troublesome dyskinesia had increased by 5.1 hours. "On" time with troublesome dyskinesia decreased an average of 0.6 hours.
"Despite the many advances that have been made over the years in treating patients with Parkinson's disease, managing motor complications such as wearing off in the advanced stages of the condition continues to be challenging for physicians, patients and their caregivers," said Dr. C.W. Olanow, M.D., Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. "Data from the various clinical trials evaluating LCIG suggest that patients with advanced Parkinson's disease may benefit from continuous intestinal infusion of levodopa and carbidopa."
The most common treatment emergent AEs were complication of device insertion (33.1 percent), abdominal pain (30.0 percent), procedural pain (21.7 percent) and nausea (16.1 percent). The most common serious treatment emergent AEs were complication of device insertion (6.5 percent), abdominal pain (3.1 percent) peritonitis (2.8 percent) and polyneuropathy (2.8 percent). Twenty-six patients (7.3 percent) withdrew due to at least one AE; 17 of these patients withdrew due to at least one serious AE. Gastrointestinal- and PEG-related issues were the most common cause of withdrawal from the study.
Phase 3 Efficacy
Functional and quality of life secondary endpoint analyses from a twelve-week double-blind, double-dummy pivotal trial of 71 patients comparing LCIG to standard levodopa-carbidopa immediate release (LC-IR) tablets were also presented. The primary endpoint of this study showed a reduction in mean daily "off" time of 4.0 hours, a statistically significant difference of 1.91 fewer hours spent in "off" time with LCIG compared to LC-IR tablets. These data were previously presented at the American Academy of Neurology Annual Meeting (April 21-28, 2012, New Orleans, Louisiana). The most common adverse events were complication of device insertion (51 percent), abdominal pain (42 percent), procedural pain (32 percent), nausea (25 percent), constipation (21 percent), orthostatic hypotension (18 percent), post-operative wound infection (17 percent), and incision site erythema (16 percent).
"We are pleased to showcase the clinical trial results being presented for LCIG in patients with advanced Parkinson's disease," said Robert Lenz, M.D., divisional vice president, Global Pharmaceutical Research and Development, Abbott. "Obtaining pivotal and supportive clinical data is a critical stage in the overall development process of LCIG and further supports our efforts to develop LCIG for advanced PD patients in the U.S. who are in need of alternative therapies."
It is estimated that at least three million people worldwide have been diagnosed with Parkinson's disease. As the disease progresses, the effect of oral medications may not last as long and can cause increasing side effects. Patients with advanced Parkinson's disease may experience fluctuations between bradykinetic (slowness of movement) and hyperdyskinetic (involuntary movement) states.
Other abstracts presented were:
Abstract 385: "Randomized, Double-blind, Double-dummy Study of Continuous Infusion of Levodopa-carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Functional and Quality-of-Life Outcomes."
Kiebertz K, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.
Abstract 436: "Levodopa-carbidopa Intestinal Gel in Parkinson's Disease Patients with Severe Motor Fluctuations: Interim Quality-of-Life Endpoints in an Ongoing, Open-label Study."
Standaert DG, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.
Abstract 410: "Stable Levodopa Plasma Levels with Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease Patients."
Nyholm D, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.
Scientists develop groundbreaking treatment for Parkinson's disease
Copied from The Northwest Parkinson’s Foundation Weekly News Update.
Fox news.com - UK scientists believe they created a groundbreaking form of therapy that could revolutionize the way Parkinson's disease is treated.
One of the patients involved in the gene-therapy trial, Sheila Roy, says it was like turning back the clock 10 years.
She is one of only 15 people worldwide to have had the new treatment, which effectively creates a medicine factory in her brain.
Parkinson's disease occurs when the brain gradually stops producing the nerve-controlling chemical dopamine. Over time, symptoms such as tremors, slow movement and stiffness get worse.
ProSavin, the new treatment, uses a "stripped-down" virus to transport dopamine-making genes into the brain. It is injected into a region called the striatum that helps control movement.
Once the virus gets into the brain cells, it reprograms them to gradually start producing their own dopamine. Roy was diagnosed with Parkinson's in her forties. After 17 years with the disease, she suffered from severe tremors, and a lack of balance made simple tasks such as writing impossible.
"People would take knives off me in the kitchen because I was everywhere with the knife," she said. "My vocal cords would suddenly shut so I can't breathe."
She added, "If I hit a wall of people, then I can't function -- I just stop -- but I'm starting to see a glimmer of the person I used to be, which is exciting."
Philip Buttery, from the Cambridge Centre for Brain Repair, in eastern England, said it was still early but that the treatment appears to be having positive results.
"It seems to be having an overall beneficial effect in smoothing out people's days, probably allowing a slight dose reduction in medication and, in some patients, a better sleep pattern and a better quality of life for all," he said.
It is not a cure, and more clinical trials are needed, he added.
The scientists at Oxford BioMedica, in southern England, also are developing gene therapy treatments for other degenerative illnesses.
Chief scientific officer Stuart Naylor said, "Rather than popping lots of tablets, the idea of a single shot therapy, single shot treatment, single shot placement of a gene therapy that provides that long-term therapeutic correction is something that hasn't been ever experienced before in medicine."
Michael J. Fox Foundation: New treatment for Parkinson's Disease
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Digital Journal - The Michael J. Fox Foundation, which was set up in the name of the actor to study Parkinson's Disease, has announced that it is to work with the ‘big pharma’ company Sanofi to look at a potential new treatment for the disease.
The Michael J. Fox Foundation and the company Sanofi have announced trials for a new treatment for Parkinson's Disease.
Parkinson’s Disease is a disorder of the brain that leads to shaking (tremors) and difficulty with walking, movement, and coordination. The Michael J. Fox Foundation (MJFF) is a charitable organization is dedicated to finding a cure for Parkinson’s disease and the development of improved therapies for those living with Parkinson’s. The organization works with the actor, Michael J. Fox, who has Parkinson’s Disease. Fox first developed the disease in 1990.
The drug company Sanofi has entered into a collaboration the MJFF to conduct a clinical trial to assess the safety and tolerability of new drug, a type of inhibitor called phosphodiesterase (coded AVE8112), which is designed to help patients with Parkinson's Disease.
According to the Top News Net, Todd Sherer, Ph.D., Chief Executive Officer of MJFF, said that the drug had:
"Shown promising pro-cognitive activity in preclinical models that could be of interest to the under-addressed cognitive aspects of Parkinson's disease, an area of unmet need where a new treatment could make a tangible difference in patients' lives. Groundbreaking collaborations with like-minded partners such as Sanofi are a hallmark of the Fox Foundation's approach and help us speed scientific advances with potential to improve the treatment of Parkinson's for patients today and in the future."
Under the terms of the collaboration, MJFF will sponsor a phase I b clinical trial to assess the safety and tolerability of AVE8112 in patients with Parkinson's disease. All data and results generated by the clinical trial will be owned by MJFF and shared with Sanofi.
To add to this, the Euro Pharma Review quotes Dr. Elias Zerhouni, President, Global R&D, Sanofi, as saying “The Michael J. Fox Foundation has been a driving force in discovering and developing improved therapies for those living with Parkinson's disease. Through this research collaboration, together we will be able to study Sanofi's pharmaceutical compound for a possible new treatment for PD patients around the world.”
Further development plans will be based upon the results of the study.