Public release date: 24-Oct-2012 [ | E-mail | Share ]

Contact: Marla Paul marla-paul@northwestern.edu 312-503-8928 Northwestern University

CHICAGO --- In an early-stage breakthrough, a team of Northwestern University scientists has developed a new family of compounds that could slow the progression of Parkinsons disease.

Parkinsons, the second most common neurodegenerative disease, is caused by the death of dopamine neurons, resulting in tremors, rigidity and difficulty moving. Current treatments target the symptoms but do not slow the progression of the disease.

The new compounds were developed by Richard B. Silverman, the John Evans Professor of Chemistry at the Weinberg College of Arts and Sciences and inventor of the molecule that became the well-known drug Lyrica, and D. James Surmeier, chair of physiology at Northwestern University Feinberg School of Medicine. Their research was published Oct. 23 in the journal Nature Communications.

The compounds work by slamming the door on an unwelcome and destructive guest -- calcium. The compounds target and shut a relatively rare membrane protein that allows calcium to flood into dopamine neurons. Surmeiers previously published research showed that calcium entry through this protein stresses dopamine neurons, potentially leading to premature aging and death. He also identified the precise protein involved -- the Cav1.3 channel.

These are the first compounds to selectively target this channel, Surmeier said. By shutting down the channel, we should be able to slow the progression of the disease or significantly reduce the risk that anyone would get Parkinsons disease if they take this drug early enough.

Weve developed a molecule that could be an entirely new mechanism for arresting Parkinsons disease, rather than just treating the symptoms, Silverman said.

The compounds work in a similar way to the drugisradipine, which is commercially available FDAapproved for treatment ofhypertension, for which a Phase 2 national clinical trial withParkinson'spatients -- led by Northwestern Medicine neurologist Tanya Simuni,M.D. -- was recentlycompleted. Isradipine studies in Parkinson's disease aremoving forward, but because isradipinewas developed for treatment ofhypertension, it interacts with other channels found in the walls ofbloodvessels. This limits the dose of the drug that can be administered to patientswithParkinson's disease.

The challenge for Silverman was to design new compounds that specifically target this rare Cav1.3 channel, not those that are abundant in blood vessels. He and colleagues first used high-throughput screening to test 60,000 existing compounds, but none did the trick.

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Parkinson's breakthough could slow disease progression

A research project underway at Lund University and funded by the Michael J. Fox Foundation will use optogenetics to monitor the effectiveness of transplanted cells in combating the effects of Parkinson's disease, the latest step in the use of the technique to study this condition.

The team led by Merab Kokaia proposes to take human skin cells and modify them to act as nerve cells, a "reprogramming" step known as transdifferentiation and which involves introducing new foreign genes into the cell.

Each cell will also be equipped with genes for a light-sensitive protein, which allows them to react when irradiated with light, in this case blue light from a laser or LED supplied via optical fiber. This responsiveness, and the ability to target it onto specific cells of interest, is the basis of optogenetics.

Once prepared, the cells will be transplanted into the brains of laboratory rats modeling Parkinson's disease.

"This is the first time such an approach is going to be used," said Kokaia. "If we get signals from the host brain as a response to light, we know that they come from the transplanted cells since they are the only ones to carry the light-sensitive protein. This gives us a much more specific way of studying the brain's reactions compared to inserting an electrode, which is the current method. With an electrode, we do not know whether the electric signals that are detected come from 'new' or 'old' brain cells."

Dopamine release One particular goal is to investigate more fully the factors affecting the release of dopamine, a chemical responsible for transmitting the signals within the brain that allow for coordination of movement, and one therefore of keen interest to researchers hoping to understand Parkinson's disease.

"The principle is that optogenetic stimulation or activation of the cells would increase release of dopamine from these cells," Kokaia commented to Optics.org. "Dopamine is the main neurotransmitter that is in short supply in Parkinson's disease, since the cells producing dopamine die. Our idea is to transform cells derived from human skin into neurons that can produce dopamine, and then use optogenetics to try to increase dopamine release from these transplanted cells."

Although this ambition might still be some way off, Kokaia believes that the approach is a sound one as a route to tackle the disease. "We know that this is long term research, but the methodology is interesting and it will be exciting to see what we can come up with," he said.

The Michael J. Fox Foundation agrees, and has provided a grant of $75,000 to the project. Established by actor Michael J. Fox in 2000, the Foundation has invested over $300 million towards combating Parkinson's disease, and is said to be the largest private funder of research into the condition in the world.

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Optogenetics assists in fight against Parkinson's disease

A research project underway at Lund University and funded by the Michael J. Fox Foundation will use optogenetics to monitor the effectiveness of transplanted cells in combating the effects of Parkinson's disease, the latest step in the use of the technique to study this condition.

The team led by Merab Kokaia proposes to take human skin cells and modify them to act as nerve cells, a "reprogramming" step known as transdifferentiation and which involves introducing new foreign genes into the cell.

Each cell will also be equipped with genes for a light-sensitive protein, which allows them to react when irradiated with light, in this case blue light from a laser or LED supplied via optical fiber. This responsiveness, and the ability to target it onto specific cells of interest, is the basis of optogenetics.

Once prepared, the cells will be transplanted into the brains of laboratory rats modeling Parkinson's disease.

"This is the first time such an approach is going to be used," said Kokaia. "If we get signals from the host brain as a response to light, we know that they come from the transplanted cells since they are the only ones to carry the light-sensitive protein. This gives us a much more specific way of studying the brain's reactions compared to inserting an electrode, which is the current method. With an electrode, we do not know whether the electric signals that are detected come from 'new' or 'old' brain cells."

Dopamine release One particular goal is to investigate more fully the factors affecting the release of dopamine, a chemical responsible for transmitting the signals within the brain that allow for coordination of movement, and one therefore of keen interest to researchers hoping to understand Parkinson's disease.

"The principle is that optogenetic stimulation or activation of the cells would increase release of dopamine from these cells," Kokaia commented to Optics.org. "Dopamine is the main neurotransmitter that is in short supply in Parkinson's disease, since the cells producing dopamine die. Our idea is to transform cells derived from human skin into neurons that can produce dopamine, and then use optogenetics to try to increase dopamine release from these transplanted cells."

Although this ambition might still be some way off, Kokaia believes that the approach is a sound one as a route to tackle the disease. "We know that this is long term research, but the methodology is interesting and it will be exciting to see what we can come up with," he said.

The Michael J. Fox Foundation agrees, and has provided a grant of $75,000 to the project. Established by actor Michael J. Fox in 2000, the Foundation has invested over $300 million towards combating Parkinson's disease, and is said to be the largest private funder of research into the condition in the world.

Go here to read the rest:
Optogenetics assists in fight against Parkinson's disease

TORONTO, ONTARIO--(Marketwire - Oct 29, 2012) - Cynapsus Therapeutics Inc. (TSX VENTURE:CTH) today announced that its APL-130277 for Parkinson''s was recognized as one of the Top Ten Neurology Projectsto Watch in 2012 by a joint selection committee including Dr. Harry Tracy, a noted authority on pharmacological interventions for diseases of the brain and editor of the highly respected biotechnology publication NeuroPerspective, as well as with Elsevier Business Intelligence, the publishers of In Vivo, Startup and The Pink Sheet.Cynapsus has been invited to present the APL-130277 Project at Elsevier''s Therapeutic Area Partnerships Meeting taking place on November 28-30, 2012 at the Westin Copley in Boston.

Criteria for selection of the Top 10 Neurology Projects to Watch in 2012 were:

APL130277 is a unique and innovative, sublingual thin film strip formulation of apomorphine. Apomorphine is an approved drug prescribed in the US, Europe and several other countries. It is administered as a subcutaneous injection or infusion to Parkinson''s patients experiencing daily "OFF" or motor fluctuation episodes. APL130277 would provide patients with a convenient and more tolerable alternative to multiple daily injections. As a new means of delivering an approved drug, this clinical stage project is expected to follow a bioequivalence regulatory and clinical path which would culminate in a New Drug Approval application in 2015.

"We are humbled to be recognized from among several hundred worthy neuroscience projects, worldwide. This is a significant honor and further independent validation of the potential of APL-130277. This comes only a few months after receiving a significant grant from The Michael J. Fox Foundation for Parkinson''s Research (MJFF) to help support our next clinical study (CTH103). The MJFF Clinical Intervention Award was provided through the Edmond J. Safra Core Programs for Parkinson''s Research," said Mr. Anthony Giovinazzo, President and Chief Executive Officer of Cynapsus."Since we started this project, we determined that there are a large number of Parkinson''s patients who would benefit from needle-free delivery of the drug.This includes patients who want a convenient alternative to a very painful injection regimen, patients who have resisted initiating therapy because of the needle issues, and the increase in PD population as a result of the growing aging baby boomer generation. These factors combined indicate that the number of Parkinson''s patients worldwide could potentially increase 2-to-3 fold over the next 8 to 10 years. This significant potential unmet medical need coupled with a short and lower risk clinical pathway would be of interest to many in global and specialty pharma, especially given that our pending patent estate, when approved and granted, would provide protection to 2031 at a minimum."

About Parkinson''s Disease

Parkinson''s disease is a chronic, degenerative neurological disorder that results from the loss of dopamineproducing nerve cells in the brain. Currenttreatments for Parkinson''s disease are able to reduce the symptoms of the disease but are not able to treat the underlying neurodegenerative processes that lead to a decline in physical and cognitive functions that affects some patients with Parkinson''s disease. It is estimated that over one million people in the United States and 5 million people globally are living with Parkinson''s disease. According to the National Institute of Neurodegenerative Disease and Stroke, the average age of onset is 60, although some people are diagnosed at age 40 or younger.

About Cynapsus Therapeutics

Cynapsus is a specialty pharmaceutical company developing the only orally administered convenient (sublingual) delivery of the only approved drug (apomorphine) to treat the motor symptoms of Parkinson''s disease. Over one million people in the United States and an estimated 5 million people globally suffer from Parkinson''s disease. Parkinson''s disease is a chronic and progressive neurodegenerative disease that impacts motor activity, and its prevalence is increasing with the aging of the population. Based on the IMPACT Registry Study and the results of Cynapsus'' Global 500 Neurologists Survey, is estimated that between 25 percent and 50 percent of patients experience "OFF episodes" in which they have impaired movement or speaking capabilities. Current medications only control the disease''s symptoms, and most drugs become less effective over time as the disease progresses.

Cynapsus'' lead drug candidate, APL130277, is an easytoadminister, fastacting reformulation of an approved drug, apomorphine, used to rescue patients from OFF episodes. Cynapsus is focused on rapidly maximizing the value of APL130277 by completing pivotal studies in advance of a New Drug Application expected to be submitted in 2015. Cynapsus anticipates outlicensing to an appropriate pharmaceutical partner before such an application is submitted.

More information about Cynapsus (TSX VENTURE:CTH) is available at http://www.cynapsus.ca and at the System for Electronic Document Analysis and Retrieval (SEDAR) at http://www.sedar.com.

Go here to see the original:
Cynapsus Therapeutics' APL 130277 for Parkinson's Chosen As One Of The Top Ten Neurology Projects To Watch For 2012

TORONTO, ONTARIO--(Marketwire - Oct 29, 2012) - Cynapsus Therapeutics Inc. (TSX VENTURE:CTH) today announced that its APL-130277 for Parkinson''s was recognized as one of the Top Ten Neurology Projectsto Watch in 2012 by a joint selection committee including Dr. Harry Tracy, a noted authority on pharmacological interventions for diseases of the brain and editor of the highly respected biotechnology publication NeuroPerspective, as well as with Elsevier Business Intelligence, the publishers of In Vivo, Startup and The Pink Sheet.Cynapsus has been invited to present the APL-130277 Project at Elsevier''s Therapeutic Area Partnerships Meeting taking place on November 28-30, 2012 at the Westin Copley in Boston.

Criteria for selection of the Top 10 Neurology Projects to Watch in 2012 were:

APL130277 is a unique and innovative, sublingual thin film strip formulation of apomorphine. Apomorphine is an approved drug prescribed in the US, Europe and several other countries. It is administered as a subcutaneous injection or infusion to Parkinson''s patients experiencing daily "OFF" or motor fluctuation episodes. APL130277 would provide patients with a convenient and more tolerable alternative to multiple daily injections. As a new means of delivering an approved drug, this clinical stage project is expected to follow a bioequivalence regulatory and clinical path which would culminate in a New Drug Approval application in 2015.

"We are humbled to be recognized from among several hundred worthy neuroscience projects, worldwide. This is a significant honor and further independent validation of the potential of APL-130277. This comes only a few months after receiving a significant grant from The Michael J. Fox Foundation for Parkinson''s Research (MJFF) to help support our next clinical study (CTH103). The MJFF Clinical Intervention Award was provided through the Edmond J. Safra Core Programs for Parkinson''s Research," said Mr. Anthony Giovinazzo, President and Chief Executive Officer of Cynapsus."Since we started this project, we determined that there are a large number of Parkinson''s patients who would benefit from needle-free delivery of the drug.This includes patients who want a convenient alternative to a very painful injection regimen, patients who have resisted initiating therapy because of the needle issues, and the increase in PD population as a result of the growing aging baby boomer generation. These factors combined indicate that the number of Parkinson''s patients worldwide could potentially increase 2-to-3 fold over the next 8 to 10 years. This significant potential unmet medical need coupled with a short and lower risk clinical pathway would be of interest to many in global and specialty pharma, especially given that our pending patent estate, when approved and granted, would provide protection to 2031 at a minimum."

About Parkinson''s Disease

Parkinson''s disease is a chronic, degenerative neurological disorder that results from the loss of dopamineproducing nerve cells in the brain. Currenttreatments for Parkinson''s disease are able to reduce the symptoms of the disease but are not able to treat the underlying neurodegenerative processes that lead to a decline in physical and cognitive functions that affects some patients with Parkinson''s disease. It is estimated that over one million people in the United States and 5 million people globally are living with Parkinson''s disease. According to the National Institute of Neurodegenerative Disease and Stroke, the average age of onset is 60, although some people are diagnosed at age 40 or younger.

About Cynapsus Therapeutics

Cynapsus is a specialty pharmaceutical company developing the only orally administered convenient (sublingual) delivery of the only approved drug (apomorphine) to treat the motor symptoms of Parkinson''s disease. Over one million people in the United States and an estimated 5 million people globally suffer from Parkinson''s disease. Parkinson''s disease is a chronic and progressive neurodegenerative disease that impacts motor activity, and its prevalence is increasing with the aging of the population. Based on the IMPACT Registry Study and the results of Cynapsus'' Global 500 Neurologists Survey, is estimated that between 25 percent and 50 percent of patients experience "OFF episodes" in which they have impaired movement or speaking capabilities. Current medications only control the disease''s symptoms, and most drugs become less effective over time as the disease progresses.

Cynapsus'' lead drug candidate, APL130277, is an easytoadminister, fastacting reformulation of an approved drug, apomorphine, used to rescue patients from OFF episodes. Cynapsus is focused on rapidly maximizing the value of APL130277 by completing pivotal studies in advance of a New Drug Application expected to be submitted in 2015. Cynapsus anticipates outlicensing to an appropriate pharmaceutical partner before such an application is submitted.

More information about Cynapsus (TSX VENTURE:CTH) is available at http://www.cynapsus.ca and at the System for Electronic Document Analysis and Retrieval (SEDAR) at http://www.sedar.com.

Go here to see the original:
Cynapsus Therapeutics' APL 130277 for Parkinson's Chosen As One Of The Top Ten Neurology Projects To Watch For 2012

/sci-tech/article/45157

A team of scientists at Northwestern University have discovered what might slow the progression of Parkinson's disease. This compound was developed by Richard B. Silverman at the Weinberg College of Arts and Sciences and creator of the molecule that became the drug Lyrica.

This compound or rather the family of compounds work by blocking calcium flow in the brains neurons. The main mechanism is the suppression of a membrane protein, which allows calcium to flow into the dopamine neurons. With this membrane protein blocking calcium flow into the dopaime neuron it avoids further cell damage.

D. James Surmeier, the chair of physiology at Northwestern previously published research which showed that calcium entry through the protein channel Cav1.3 stresses the dopamine neurons which could potentially lead to premature aging and death. The research team at Northwestern has previously published research showing how calcium entry through the protein channel Cav1.3 stresses the dopamine neurons, which has been shown to lead to premature aging and death.

"We've developed a molecule that could be an entirely new mechanism for arresting Parkinson's disease, rather than just treating the symptoms," Silverman explained.

A Phase 2 national clinical trail with Parkinson's patients was led by Northwestern Medicine neurologist Tanya Simuni, M.D. The new compound works in a similar way as the drug Isradipine (A calcium channel blocker used to reduce risk of stroke and heart attack). However Irasdiphine interacts with other channels found in the walls of blood vessels and Isradipine can not be used in a high enough concentration to be effective against Parkinson's.

One challenge for Silverman was in creating a new compound that would specifically target the rare Cav1.3 channel. He and his colleagues did a high-throughput screening to test 60,000 existing compounds, none of which did what Silverman required. Subsequently, Silverman looked at compounds he had developed for other neurodegenerative diseases and identified one compound he believed had promise. Soosung Kang, a postdoctoral associate in Silverman's lab was tasked with refining the molecules until they where able to only shut the Cav1.3. It took Mr. Kang 9 months to finally succeed.

"The drug relived the stress on the cells," Surmeier said. "We have a long way to go before we are ready to give this drug, or a reasonable facsimile, to humans, but we are very encouraged,"

The next step for the Northwestern team is to improve the pharmacology of the compounds to make them suitable for human use and eventually move to Phase 1 clinical trials.

See original here:
Slowing Down Parkinson's

/sci-tech/article/45157

A team of scientists at Northwestern University have discovered what might slow the progression of Parkinson's disease. This compound was developed by Richard B. Silverman at the Weinberg College of Arts and Sciences and creator of the molecule that became the drug Lyrica.

This compound or rather the family of compounds work by blocking calcium flow in the brains neurons. The main mechanism is the suppression of a membrane protein, which allows calcium to flow into the dopamine neurons. With this membrane protein blocking calcium flow into the dopaime neuron it avoids further cell damage.

D. James Surmeier, the chair of physiology at Northwestern previously published research which showed that calcium entry through the protein channel Cav1.3 stresses the dopamine neurons which could potentially lead to premature aging and death. The research team at Northwestern has previously published research showing how calcium entry through the protein channel Cav1.3 stresses the dopamine neurons, which has been shown to lead to premature aging and death.

"We've developed a molecule that could be an entirely new mechanism for arresting Parkinson's disease, rather than just treating the symptoms," Silverman explained.

A Phase 2 national clinical trail with Parkinson's patients was led by Northwestern Medicine neurologist Tanya Simuni, M.D. The new compound works in a similar way as the drug Isradipine (A calcium channel blocker used to reduce risk of stroke and heart attack). However Irasdiphine interacts with other channels found in the walls of blood vessels and Isradipine can not be used in a high enough concentration to be effective against Parkinson's.

One challenge for Silverman was in creating a new compound that would specifically target the rare Cav1.3 channel. He and his colleagues did a high-throughput screening to test 60,000 existing compounds, none of which did what Silverman required. Subsequently, Silverman looked at compounds he had developed for other neurodegenerative diseases and identified one compound he believed had promise. Soosung Kang, a postdoctoral associate in Silverman's lab was tasked with refining the molecules until they where able to only shut the Cav1.3. It took Mr. Kang 9 months to finally succeed.

"The drug relived the stress on the cells," Surmeier said. "We have a long way to go before we are ready to give this drug, or a reasonable facsimile, to humans, but we are very encouraged,"

The next step for the Northwestern team is to improve the pharmacology of the compounds to make them suitable for human use and eventually move to Phase 1 clinical trials.

See original here:
Slowing Down Parkinson's

Ever since Roy Roden was diagnosed with Parkinsons disease three years ago, hes been on a race to get the most out of life while his body still can.

He has skydived, traveled, zip-lined.

Now, the South Florida native is putting his relay into higher gear, planting his foot firmly on a bike pedal.

Roden and his wife Lynn, of North Miami Beach, will take off Thursday with their two dogs on a cross-country bike ride from Seattle to Miami, to raise awareness and money for Parkinsons.

If you found out you have a degenerative disease, what are you going to do with the next 10 years of your life? Roden said. I want to do something.

Roden, 54, plans to spread the word about clinical trials and share his experience with his most recent treatment, deep brain stimulation.

His doctors are behind him.

I give it the thumbs up, said Dr. Carlos Singer, professor of neurology at the University of Miami School of Medicine and division chief of Parkinsons and movement disorders. It can be inspiring to people. Its neat. It shows how active a person with Parkinsons can be.

A progressive, neurodegenerative brain disorder, Parkinsons is the second most common degenerative disease of the brain, after Alzheimers. It affects one million people in the United States, including an estimated 35,000 in South Florida, according to the National Parkinson Foundation, which is based in Miami.

Each year, about 50,000 to 60,000 cases of Parkinsons are diagnosed, with an average age at diagnosis of 62.

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Couple to bike cross-country for Parkinson’s charities