Newswise BIRMINGHAM, Ala. For decades, patients with Parkinsons disease (PD) have had the same experience. Their hands start to shake uncontrollably, their limbs become rigid and they lose their balance. Years before those movement problems set in, many begin struggling with fainting, incontinence, sexual dysfunction, anxiety and depression. Many patients are still treated with a 42-year-old drug called L-DOPA, which temporarily staves off symptoms but can itself cause heart arrhythmias, stomach bleeding and hallucinations.

This punishing experience may explain in part why patients with PD die at twice the rate of those without the disease in the years after their diagnosis. In this light, its best to tread carefully when talking about early study results that promise something better. That said, a team of researchers at the University of Alabama at Birmingham is excited.

The UAB team has identified a set of experimental drugs called LRRK2 inhibitors that may go beyond symptom relief to directly counter the inflammation and nerve cell death at the root of Parkinsons. At least, these effects have been suggested in mouse and cell culture studies meant to approximate human disease. UAB researchers reported on these findings today in a presentation at Neuroscience 2012, the annual meeting of the Society for Neuroscience in New Orleans.

We dont yet know what percentage of patients might benefit from LRKK2 inhibitors, but LRRK2 is without a doubt the most exciting target for neuroprotection to have ever been identified in Parkinsons disease, says Andrew West, Ph.D., associate professor in the Department of Neurology within the UAB School of Medicine, who gave the presentation at Neuroscience 2012. We will repeat our experiments many times before drawing final conclusions, but our ultimate goal is see our compound or something like it enter toxicology studies, and ultimately, clinical trials as soon as is prudent.

While Wests compounds are promising, they still face many crucial tests that will decide whether or not they reach human trials. But the field is excited, because this is the first time such a drug target has been found for any neurodegenerative disease. Along with evidence that LRRK2 plays a crucial role in the mechanisms of Parkinsons disease, it is a protein kinase, the same kind of enzyme (although not the same one) that has been safely and potently targeted by existing treatments for other diseases, including the cancer drugs Herceptin, Tarceva and Erbitux.

Why LRRK2? LRRK2 stands for leucine-rich repeat kinase 2. Kinases are enzymes that attach molecules called phosphates to other molecules to start, stop or adjust cellular processes. Past studies found that the most common LRRK2 mutation, called G2019S, makes LRRK2 slightly over-active. The idea is to dial LRRK2 back with drugs.

Whether its a bad version of a gene, an unlucky flu infection, a head injury or just age, something makes a protein called alpha-synuclein build up in the nerve cells of Parkinsons patients, contributing to their self-destruction. Unfortunately, alpha-synuclein and proteins like it are not part of a traditional set of drug-able targets. Once alpha-synuclein builds up, the question becomes whether the brain will handle it well or amplify the disease.

LRRK2, to Wests mind, is a critical decision-maker in the bodys answer to that question. He thinks it operates at the intersection between alpha-synuclein, neurotransmission and immune responses, which fight infectious diseases but also create disease-related inflammation when unleashed at the wrong moment, or in the wrong place or amount. Not everyone who has a LRRK2 mutation develops the disease, but Wests team thinks it becomes important when combined with other factors.

Past studies have shown that alpha-synuclein build-up in nerve cells activates nearby immune cells of the brain called microglia, and that these microglia express high levels of LRRK2. Recent cell studies in Wests lab suggest that mutated, overactive LRRK2 strengthens inflammatory responses in microglia and that inhibiting LRRK2 reduces them. Preliminary data also suggests LRRK2-driven inflammation raises the rate of nerve cell death. Its worth noting, however, that neither these mechanisms nor their relationships with each other and Parkinsons disease have been fully confirmed.

The beauty is that we dont necessarily need to confirm an exact mechanism to move drugs into clinical trials, says West. One could argue that human PD is too complex to fully model in other animals. Many predict that we will not know if we understand Parkinsons disease until we get safe, potent, specific drugs into human studies and until one of them halts or reverses the disease process.

Read the original:
UAB Team Sets Sights on Neuroprotective Treatment for Parkinson's Disease

Newswise BIRMINGHAM, Ala. For decades, patients with Parkinsons disease (PD) have had the same experience. Their hands start to shake uncontrollably, their limbs become rigid and they lose their balance. Years before those movement problems set in, many begin struggling with fainting, incontinence, sexual dysfunction, anxiety and depression. Many patients are still treated with a 42-year-old drug called L-DOPA, which temporarily staves off symptoms but can itself cause heart arrhythmias, stomach bleeding and hallucinations.

This punishing experience may explain in part why patients with PD die at twice the rate of those without the disease in the years after their diagnosis. In this light, its best to tread carefully when talking about early study results that promise something better. That said, a team of researchers at the University of Alabama at Birmingham is excited.

The UAB team has identified a set of experimental drugs called LRRK2 inhibitors that may go beyond symptom relief to directly counter the inflammation and nerve cell death at the root of Parkinsons. At least, these effects have been suggested in mouse and cell culture studies meant to approximate human disease. UAB researchers reported on these findings today in a presentation at Neuroscience 2012, the annual meeting of the Society for Neuroscience in New Orleans.

We dont yet know what percentage of patients might benefit from LRKK2 inhibitors, but LRRK2 is without a doubt the most exciting target for neuroprotection to have ever been identified in Parkinsons disease, says Andrew West, Ph.D., associate professor in the Department of Neurology within the UAB School of Medicine, who gave the presentation at Neuroscience 2012. We will repeat our experiments many times before drawing final conclusions, but our ultimate goal is see our compound or something like it enter toxicology studies, and ultimately, clinical trials as soon as is prudent.

While Wests compounds are promising, they still face many crucial tests that will decide whether or not they reach human trials. But the field is excited, because this is the first time such a drug target has been found for any neurodegenerative disease. Along with evidence that LRRK2 plays a crucial role in the mechanisms of Parkinsons disease, it is a protein kinase, the same kind of enzyme (although not the same one) that has been safely and potently targeted by existing treatments for other diseases, including the cancer drugs Herceptin, Tarceva and Erbitux.

Why LRRK2? LRRK2 stands for leucine-rich repeat kinase 2. Kinases are enzymes that attach molecules called phosphates to other molecules to start, stop or adjust cellular processes. Past studies found that the most common LRRK2 mutation, called G2019S, makes LRRK2 slightly over-active. The idea is to dial LRRK2 back with drugs.

Whether its a bad version of a gene, an unlucky flu infection, a head injury or just age, something makes a protein called alpha-synuclein build up in the nerve cells of Parkinsons patients, contributing to their self-destruction. Unfortunately, alpha-synuclein and proteins like it are not part of a traditional set of drug-able targets. Once alpha-synuclein builds up, the question becomes whether the brain will handle it well or amplify the disease.

LRRK2, to Wests mind, is a critical decision-maker in the bodys answer to that question. He thinks it operates at the intersection between alpha-synuclein, neurotransmission and immune responses, which fight infectious diseases but also create disease-related inflammation when unleashed at the wrong moment, or in the wrong place or amount. Not everyone who has a LRRK2 mutation develops the disease, but Wests team thinks it becomes important when combined with other factors.

Past studies have shown that alpha-synuclein build-up in nerve cells activates nearby immune cells of the brain called microglia, and that these microglia express high levels of LRRK2. Recent cell studies in Wests lab suggest that mutated, overactive LRRK2 strengthens inflammatory responses in microglia and that inhibiting LRRK2 reduces them. Preliminary data also suggests LRRK2-driven inflammation raises the rate of nerve cell death. Its worth noting, however, that neither these mechanisms nor their relationships with each other and Parkinsons disease have been fully confirmed.

The beauty is that we dont necessarily need to confirm an exact mechanism to move drugs into clinical trials, says West. One could argue that human PD is too complex to fully model in other animals. Many predict that we will not know if we understand Parkinsons disease until we get safe, potent, specific drugs into human studies and until one of them halts or reverses the disease process.

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UAB Team Sets Sights on Neuroprotective Treatment for Parkinson's Disease

Public release date: 17-Oct-2012 [ | E-mail | Share ]

Contact: Jessica Mikulski jessica.mikulski@uphs.upenn.edu 215-349-8369 University of Pennsylvania School of Medicine

PHILADELPHIA - Changes in the ability to smell and taste can be caused by a simple cold or upper respiratory tract infection, but they may also be among the first signs of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Now, new research from the Perelman School of Medicine at the University of Pennsylvania has revealed an association between an impaired sense of smell and myasthenia gravis (MG), a chronic autoimmune neuromuscular disease characterized by fluctuating fatigue and muscle weakness. The findings are published in the latest edition of PLOS ONE.

"This study demonstrates, for the first time, that myasthenia gravis is associated with profound dysfunction of the olfactory system dysfunction equivalent to that observed in Alzheimer's disease and Parkinson's disease," said senior study author Richard Doty, PhD, director of the Smell and Taste Center at Penn. "The results are the strongest evidence to date that myasthenia gravis, once thought of as solely a disorder of the peripheral nervous system, involves the brain as well."

The general notion that MG is strictly a peripheral nervous system disease stems, in part, from early observations that the disorder is not accompanied by obvious brain pathology. Behavioral and physiological evidence that has been presented in support of MG's involvement in the central nervous system (CNS) has frequently been discounted due to lack of replicability of findings. For example, while some studies have found MG-related deficits in verbal memory, relative to controls, others have not. Nevertheless, scientists have continued to report CNS-related dysfunctions in MG, including visual and auditory deficiencies in this disease. Further, EEG tests have shown abnormalities in MG patients and MG-related antibodies have been detected in cerebrospinal fluid of patients.

In order to further explore the role of the central nervous system in MG, Doty and colleagues employed a smell test that has been used to assess the underlying connection between sense of smell and other neurodegenerative diseases.

"Our sense of smell is directly linked to numerous functions of the brain," says Doty, one of the original researchers who made the connection between loss of smell and Parkinson's disease. "Olfaction is a good model system for other, more complicated, brain circuits. Understanding our sense of smell, or lack thereof, offers broader insights into brain functions and diseases stemming from the brain."

In the current study, 27 MG patients were individually matched for age and sex to 27 normal controls. Eleven patients with polymyositis, a disorder with debilitating muscle symptoms similar to those of MG, also were tested. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT), a picture test that is equivalent in content and form to the UPSIT designed to control for non-olfactory cognitive deficits. The research team also monitored each patient during the UPSIT and found no impaired ability to inhale, ruling out physical impediments to sniffing the odors.

Researchers found that the UPSIT scores of the MG patients were significantly lower than those of the age- and sex-matched normal controls, as well as the patients with polymyositis. Of the MG patients, only 15 percent were even aware of a smell problem before testing.

"The marked difference in smell dysfunction between the MG patients and the controls cannot be explained by any other physical or cognitive differences," says Doty. "Although we are still exploring the physiological basis of this dysfunction in MG, it's important to note that the extent of the diminished ability to identify odors found in this study is of the same magnitude as that observed in a range of CNS-related diseases, including Alzheimer's and Parkinson's."

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Association between rare neuromuscular disorder and loss of smell, Penn Study finds

Published: Wednesday, October 17, 2012 at 5:40 p.m. Last Modified: Wednesday, October 17, 2012 at 5:40 p.m.

A decade ago, deep-brain stimulation for Parkinsons disease was considered a risky procedure. Today, its on the cutting edge of personalized medicine, and researchers at the University of Floridas McKnight Brain Institute are at the forefront of its evolution.

When we started in 2002, there were only a handful of places in the U.S. that did it. There was a lot of skepticism about the operation from internists and neurologists, said Dr. Michael Okun, a neurologist at UF. Now it has gone from crazy to cool to completely accepted.

Okun published an article today in the New England Journal of Medicine that explains how the procedure is helping with Parkinsons disease and other neurological conditions such as obsessive compulsive disorder, Tourettes syndrome and depression.

Okun and Dr. Kelly Foote, a neurosurgeon at UF, have performed more than 800 procedures in the past decade, mostly in Parkinsons patients whose medications have become less effective, leading to complications such as on-off fluctuations.

During the off periods, the medication stops working and patients symptoms such as tremors or immobility worsen. This happens in most patients after about five years, said Okun, and patients with off periods of more than three hours a day are good candidates for deep-brain stimulation.

During the procedure, doctors first identify the part of the brain to target. For most patients, that will be either the subthalamic nucleus or the globus pallidus, two tiny sites involved in controlling movement.

Doctors then drill a dime-sized hole in the skull so they can place a lead that delivers electric current to the troublesome spot responsible for the degeneration caused by the disease.

You want to make sure that you take your time and get it right. Those leads have to be within a half-millimeter to work their magic, Okun said.

Deciding where to place the lead also depends on the patient. If you see a patient and tremors are important maybe they are a dentist or a chef, they might choose one target in the brain. If its a singer or trial litigator, they may target another part of the brain.

Continued here:
UF: Deep-brain stimulation helping with OCD, Tourette's, along with Parkinson's

Published: Wednesday, October 17, 2012 at 5:40 p.m. Last Modified: Wednesday, October 17, 2012 at 5:40 p.m.

A decade ago, deep-brain stimulation for Parkinsons disease was considered a risky procedure. Today, its on the cutting edge of personalized medicine, and researchers at the University of Floridas McKnight Brain Institute are at the forefront of its evolution.

When we started in 2002, there were only a handful of places in the U.S. that did it. There was a lot of skepticism about the operation from internists and neurologists, said Dr. Michael Okun, a neurologist at UF. Now it has gone from crazy to cool to completely accepted.

Okun published an article today in the New England Journal of Medicine that explains how the procedure is helping with Parkinsons disease and other neurological conditions such as obsessive compulsive disorder, Tourettes syndrome and depression.

Okun and Dr. Kelly Foote, a neurosurgeon at UF, have performed more than 800 procedures in the past decade, mostly in Parkinsons patients whose medications have become less effective, leading to complications such as on-off fluctuations.

During the off periods, the medication stops working and patients symptoms such as tremors or immobility worsen. This happens in most patients after about five years, said Okun, and patients with off periods of more than three hours a day are good candidates for deep-brain stimulation.

During the procedure, doctors first identify the part of the brain to target. For most patients, that will be either the subthalamic nucleus or the globus pallidus, two tiny sites involved in controlling movement.

Doctors then drill a dime-sized hole in the skull so they can place a lead that delivers electric current to the troublesome spot responsible for the degeneration caused by the disease.

You want to make sure that you take your time and get it right. Those leads have to be within a half-millimeter to work their magic, Okun said.

Deciding where to place the lead also depends on the patient. If you see a patient and tremors are important maybe they are a dentist or a chef, they might choose one target in the brain. If its a singer or trial litigator, they may target another part of the brain.

Continued here:
UF: Deep-brain stimulation helping with OCD, Tourette's, along with Parkinson's

Pilot Study in Neurosurgery Shows Safety and Benefits of Extradural Stimulation

Newswise Philadelphia, Pa. (October 16, 2012) Electrical stimulation using extradural electrodesplaced underneath the skull but not implanted in the brainis a safe approach with meaningful benefits for patients with Parkinson's disease, reports the October issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The technique, called extradural motor cortex stimulation (EMCS), may provide a less-invasive alternative to electrical deep brain stimulation (DBS) for some patients with the movement disorder Parkinson's disease. The study was led by Dr. Beatrice Cioni of Catholic University, Rome.

Study Shows Safety and Effectiveness of Extradural Brain Stimulation The researchers evaluated EMCS in nine patients with Parkinson's disease. Over the past decade, DBS using electrodes implanted in specific areas within the brain has become an accepted treatment for Parkinson's disease. In the EMCS technique, a relatively simple surgical procedure is performed to place a strip of four electrodes in an "extradural" locationon top of the tough membrane (dura) lining the brain.

The electrodes were placed over a brain area called the motor cortex, which governs voluntary muscle movements. The study was designed to demonstrate the safety of the EMCS approach, and to provide preliminary information on its effectiveness in relieving the various types of movement abnormalities in Parkinson's disease.

The electrode placement procedure and subsequent electrical stimulation were safe, with no surgical complications or other adverse events. In particular, the patients had no changes in intellectual function or behavior and no seizures or other signs of epilepsy.

Extradural stimulation led to small but significant and lasting improvements in control of voluntary movement. After one year, motor symptoms improved by an average of 13 percent on a standard Parkinson's disease rating scale, while the patient was off medications.

'Remarkable' Improvement in Walking and Related Symptoms The improvement appeared after three to four weeks of electrical stimulation and persisted for a few weeks after stimulation was stopped. In one case where the stimulator was accidentally switched off, it took four weeks before the patient even noticed.

Extradural stimulation was particularly effective in relieving the "axial" symptoms of Parkinson's disease, such as difficulties walking. Patients had significant improvement in walking ability, including fewer problems with "freezing" of gait. The EMCS procedure also reduced tremors and other abnormal movements while improving scores on a quality-of-life questionnaire.

Although DBS is an effective treatment for Parkinson's disease, it's not appropriate for all patients. Some patients have health conditions or old age that would make surgery for electrode placement too risky. Other patientsincluding four of the nine patients in the new studyare eligible for DBS but don't want to undergo electrode placement surgery.

See the original post here:
Less-Invasive Method of Brain Stimulation Helps Patients with Parkinson's Disease

Pilot Study in Neurosurgery Shows Safety and Benefits of Extradural Stimulation

Newswise Philadelphia, Pa. (October 16, 2012) Electrical stimulation using extradural electrodesplaced underneath the skull but not implanted in the brainis a safe approach with meaningful benefits for patients with Parkinson's disease, reports the October issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The technique, called extradural motor cortex stimulation (EMCS), may provide a less-invasive alternative to electrical deep brain stimulation (DBS) for some patients with the movement disorder Parkinson's disease. The study was led by Dr. Beatrice Cioni of Catholic University, Rome.

Study Shows Safety and Effectiveness of Extradural Brain Stimulation The researchers evaluated EMCS in nine patients with Parkinson's disease. Over the past decade, DBS using electrodes implanted in specific areas within the brain has become an accepted treatment for Parkinson's disease. In the EMCS technique, a relatively simple surgical procedure is performed to place a strip of four electrodes in an "extradural" locationon top of the tough membrane (dura) lining the brain.

The electrodes were placed over a brain area called the motor cortex, which governs voluntary muscle movements. The study was designed to demonstrate the safety of the EMCS approach, and to provide preliminary information on its effectiveness in relieving the various types of movement abnormalities in Parkinson's disease.

The electrode placement procedure and subsequent electrical stimulation were safe, with no surgical complications or other adverse events. In particular, the patients had no changes in intellectual function or behavior and no seizures or other signs of epilepsy.

Extradural stimulation led to small but significant and lasting improvements in control of voluntary movement. After one year, motor symptoms improved by an average of 13 percent on a standard Parkinson's disease rating scale, while the patient was off medications.

'Remarkable' Improvement in Walking and Related Symptoms The improvement appeared after three to four weeks of electrical stimulation and persisted for a few weeks after stimulation was stopped. In one case where the stimulator was accidentally switched off, it took four weeks before the patient even noticed.

Extradural stimulation was particularly effective in relieving the "axial" symptoms of Parkinson's disease, such as difficulties walking. Patients had significant improvement in walking ability, including fewer problems with "freezing" of gait. The EMCS procedure also reduced tremors and other abnormal movements while improving scores on a quality-of-life questionnaire.

Although DBS is an effective treatment for Parkinson's disease, it's not appropriate for all patients. Some patients have health conditions or old age that would make surgery for electrode placement too risky. Other patientsincluding four of the nine patients in the new studyare eligible for DBS but don't want to undergo electrode placement surgery.

See the original post here:
Less-Invasive Method of Brain Stimulation Helps Patients with Parkinson's Disease

The sixth annual North Shore Walk for Parkinsons Disease will be held on Saturday, Oct. 20. The 3-mile walk starts at the First Church Congregational, 40 Monument Ave. in Swampscott. Registration is $25 and starts at 10 a.m.; the walk begins at 10:30 a.m. Free T-shirts will be provided for the first 100 walkers.

The North Shore Walk for Parkinsons Disease was started by the Wistran family of Swampscott in honor of Dr. Daniel Wistran, who has been battling Parkinsons disease since 1997.

All donations support the Michael J. Fox Foundation, which is dedicated to finding a cure for Parkinsons disease within the decade. Five million people worldwide are living with Parkinsons disease a chronic, degenerative neurological disorder. In the United States, 60,000 new cases will be diagnosed this year alone. There is no known cure for Parkinsons disease.

For more information, call 781-307-5804 or email northshorewalk@gmail.com. Donations may be made online teamfox.org/goto/northshorewalk.

View original post here:
Parkinson’s walk set for Saturday in Swampscott

CAMBRIDGE, Mass., Oct.17, 2012 /PRNewswire/ --NeuroPhage Pharmaceuticals, Inc. announced today positive data with NPT001 in an alpha-synuclein pre-clinical model for Parkinson's disease (PD). The study was funded by The Michael J. Fox Foundation (MJFF). NPT001 is a first-in-class drug candidate with potential disease-modifying activity that disrupts and clears a variety of amyloid aggregates in the brain. In addition to reducing beta amyloid and tau aggregates in Alzheimer's disease (AD) preclinical studies, the new study demonstrates that NPT001 disrupts alpha-synuclein fibrils which are thought to play a critical role in PD.

The study was conducted in collaboration with Dr. Eliezer Masliah at the University of California San Diego (UCSD) and demonstrated that a single NPT001 treatment produced significant reductions in neuropathology along with improved motor performance in the PD model. Specifically, NPT001 significantly reduced alpha-synuclein deposits in the brain and restored dopamine-producing cells to normal function. Deficits in dopamine production are responsible for many of the behavioral dysfunctions in PD. In addition, NPT001 was well-tolerated and produced no observable adverse effects.

The data will be presented at the upcoming 2013 ADPD meeting in Florence, Italy. "The effects produced by NPT001 are robust and impressive, and the treatment improved the critical functions that are impaired in the brain of Parkinson patients," said Dr. Franz Hefti, PD expert and Chairman of NeuroPhage's Scientific Advisory Board.

"We are excited by the results of this study showing dose-dependent amelioration of neuropathology and functional improvement in a Parkinson's disease pre-clinical model following treatment with NPT001. These results, taken together with our biochemical and cell data for alpha-synuclein, support the development of NPT001 for PD in addition to the ongoing clinical development for Alzheimer's disease," said Dr. Kimberley S. Gannon, NeuroPhage's Senior Vice President of Preclinical Research & Development.

NeuroPhage's technology platform permits the development of therapeutics that target multiple misfolded proteins involved in neurodegeneration such as beta amyloid and tau (involved in AD), as well as alpha-synuclein (involved in PD). In February 2012, NeuroPhage announced that it had received a grant from MJFF for PD research on NPT001.

About Parkinson's Disease

Parkinson's disease is a chronic, progressive disorder of the central nervous system and results from the loss of cells in an area of the brain called the substantia nigra. These cells produce dopamine, a chemical messenger responsible for transmitting signals within the brain. Loss of dopamine causes critical nerve cells in the brain, or neurons, to fire out of control, leaving patients unable to direct or control their movement in a normal manner. The symptoms of Parkinson's may include tremors, difficulty maintaining balance and gait, rigidity or stiffness of the limbs and trunk, and general slowness of movement (also called bradykinesia). Patients may also eventually have difficulty walking, talking, or completing other simple tasks. Symptoms often appear gradually yet with increasing severity, and the progression of the disease may vary widely from patient to patient. There is no cure for Parkinson's disease. Drugs have been developed that can help patients manage many of the symptoms; however they do not prevent disease progression.

About The Michael J. Fox Foundation

The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today. The Foundation has funded over $304 million in research to date.

About NeuroPhage

More here:
NeuroPhage Reports Beneficial Effects of its Drug Candidate in a Pre-clinical Study of Parkinson's Disease Funded by ...

CAMBRIDGE, Mass., Oct.17, 2012 /PRNewswire/ --NeuroPhage Pharmaceuticals, Inc. announced today positive data with NPT001 in an alpha-synuclein pre-clinical model for Parkinson's disease (PD). The study was funded by The Michael J. Fox Foundation (MJFF). NPT001 is a first-in-class drug candidate with potential disease-modifying activity that disrupts and clears a variety of amyloid aggregates in the brain. In addition to reducing beta amyloid and tau aggregates in Alzheimer's disease (AD) preclinical studies, the new study demonstrates that NPT001 disrupts alpha-synuclein fibrils which are thought to play a critical role in PD.

The study was conducted in collaboration with Dr. Eliezer Masliah at the University of California San Diego (UCSD) and demonstrated that a single NPT001 treatment produced significant reductions in neuropathology along with improved motor performance in the PD model. Specifically, NPT001 significantly reduced alpha-synuclein deposits in the brain and restored dopamine-producing cells to normal function. Deficits in dopamine production are responsible for many of the behavioral dysfunctions in PD. In addition, NPT001 was well-tolerated and produced no observable adverse effects.

The data will be presented at the upcoming 2013 ADPD meeting in Florence, Italy. "The effects produced by NPT001 are robust and impressive, and the treatment improved the critical functions that are impaired in the brain of Parkinson patients," said Dr. Franz Hefti, PD expert and Chairman of NeuroPhage's Scientific Advisory Board.

"We are excited by the results of this study showing dose-dependent amelioration of neuropathology and functional improvement in a Parkinson's disease pre-clinical model following treatment with NPT001. These results, taken together with our biochemical and cell data for alpha-synuclein, support the development of NPT001 for PD in addition to the ongoing clinical development for Alzheimer's disease," said Dr. Kimberley S. Gannon, NeuroPhage's Senior Vice President of Preclinical Research & Development.

NeuroPhage's technology platform permits the development of therapeutics that target multiple misfolded proteins involved in neurodegeneration such as beta amyloid and tau (involved in AD), as well as alpha-synuclein (involved in PD). In February 2012, NeuroPhage announced that it had received a grant from MJFF for PD research on NPT001.

About Parkinson's Disease

Parkinson's disease is a chronic, progressive disorder of the central nervous system and results from the loss of cells in an area of the brain called the substantia nigra. These cells produce dopamine, a chemical messenger responsible for transmitting signals within the brain. Loss of dopamine causes critical nerve cells in the brain, or neurons, to fire out of control, leaving patients unable to direct or control their movement in a normal manner. The symptoms of Parkinson's may include tremors, difficulty maintaining balance and gait, rigidity or stiffness of the limbs and trunk, and general slowness of movement (also called bradykinesia). Patients may also eventually have difficulty walking, talking, or completing other simple tasks. Symptoms often appear gradually yet with increasing severity, and the progression of the disease may vary widely from patient to patient. There is no cure for Parkinson's disease. Drugs have been developed that can help patients manage many of the symptoms; however they do not prevent disease progression.

About The Michael J. Fox Foundation

The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today. The Foundation has funded over $304 million in research to date.

About NeuroPhage

More here:
NeuroPhage Reports Beneficial Effects of its Drug Candidate in a Pre-clinical Study of Parkinson's Disease Funded by ...

The nuclei of brain stem cells in some Parkinson's patients become misshapen with age. The discovery opens up new ways to target the disease.

Nubby nucleus: Brain cells from a deceased Parkinsons patient have deformed nuclei (bottom) compared with normal brain cells from an individual of a similar age. Merce Marti and Juan Carlos Izpisua Belmonte

Stem cells in the brains of some Parkinson's patients are increasingly damaged as they age, an effect that eventually diminishes their ability to replicate and differentiate into mature cell types. Researchers studied neural stem cells created from patients' own skin cells to identify the defects. The findings offer a new focus for therapeutics that target the cellular change.

The report, published today in Nature, takes advantage of the ability to model diseases in cell culture by turning patient's own cells first into so-called induced pluripotent stem cells and then into disease-relevant cell typesin this case, neural stem cells. The basis of these techniques was recognized with a Nobel Prize in medicine last week.

The authors studied cells taken from patients with a heritable form of Parkinson's that stems from mutations in a gene. After growing several generation of neural stem cells derived from patients with that mutation, they saw the cell nuclei start to develop abnormal shapes. Those abnormalities compromise the survival of the neural stem cells, says study coauthor Ignacio Sancho-Martinez of the Salk Institute for Biological Studies in La Jolla, California.

Today's study "brings to light a new avenue for trying to figure out the mechanism of Parkinson's," says Scott Noggle of the New York Stem Cell Foundation. It also provides a new set of therapeutic targets: "Drugs that target or modify the activity [of the gene] could be applicable to Parkinson's patients. This gives you a handle on what to start designing drug screens around."

The strange nuclei were also seen in patients who did not have a known genetic basis for Parkinson's disease. The authors suggest this indicates that dysfunctional neural stem cells could contribute to Parkinson's. While that conclusion is "highly speculative," says Ole Isacson, a neuroscientist at Harvard Medical School, the study demonstrates the "wealth of data and information that we now can gain from iPS cells."

See original here:
Parkinson's cells