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I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's diseases as well and thought it would be nice to have a place where updated news is in one place. That is why I began this blog.
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Saturday, March 7, 2015
Thursday, March 5, 2015
By B. D. Colen, Harvard Staff Writer
March 3, 2015
Harvard Stem Cell Institute (HSCI) researchers at University-affiliated McLean Hospital have taken what they describe as an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson’s disease.
Ole Isacson and colleagues reported that dopamine-producing neurons derived from the skin cells of primates survived for more than two years after implantation into one of the animals, and markedly reduced its Parkinson’s symptoms. The primate did not require immunosuppression, the scientists reported in the journal Cell Stem Cell.
Penelope J. Hallett, an assistant professor of psychiatry at Harvard Medical School (HMS) who works at McLean with Isacson, is the first author on the paper.
Such positive results were only seen in one animal because the experimental protocols evolved and were improved over time. Originally, the experiments were conducted using neurons derived from embryonic stem cells, which required using immunosuppressive drugs in the animals, and did not produce results that were as positive.
The current experiments used induced pluripotent stem cells, or iPS cells, which use a patient’s own skin cells to create the stem cells and then the neurons, so the patient — or in this case, the primate — does not recognize the new dopamine-producing neurons as foreign and reject them.
“It’s very difficult to get cell survival in primates,” said Isacson, who has been refining his experiments for more than 15 years. “This is a very high bar to clear.” Isacson is an HSCI principal faculty member, an HMS professor of neurology, and director of the Center for Neuroregeneration Research/ Neuroregeneration Laboratories at McLean.
Isacson said the conclusion of this experiment marks “the first time that an animal has recovered to the same activity level he had before.” He noted that the animal was “able to move as fast around its home cage” as an animal without Parkinson’s, and had normal agility, though individual motions were still slowed by the disease.
In this latest experiment, the neurons were implanted into only one side of the animals’ brains, and the improvements were seen on the opposite side, as would be expected.
Parkinson’s, which may affect as many as 1 million Americans, is caused by a depletion of dopamine-producing neurons in the brain. The disease causes a range of symptoms, from mild tremors to dementia and death, and can include slowed movements, muscle rigidity, tremors, changes in speech, loss of autonomic movement, and related issues. Current treatments include medications, electrical implants in the brain, and, in a limited number of cases, fetal neuron transplants.
Isacson stressed that there are a number of technical hurdles to be cleared before his team will be ready for its first clinical trial. He said he and Kevin Eggan, another HSCI principal faculty member working on neurological diseases, as well as other Harvard clinicians “will have to establish a protocol we believe will be safe and desirable from a clinical standpoint.”
“Conservatively, I’d say we’re three years” from requesting the go-ahead from the U.S. Food and Drug Administration for a Phase 1 clinical trial, Isacson said.
“Our next year will be dedicated to making cells” free of contaminants, creating a matrix on which to grow cells that “is free of any animal proteins,” and establishing a cell-freezing protocol, which will be necessary for transporting and storing the cells. Additionally, he said, the researchers need to perfect cell-sorting technology.
The current experiments were funded by HSCI and the Harvard Miller Consortium.
March 3, 2015
Carnegie Mellon University
Neuroscientists have identified a new pathway by which several brain areas communicate within the brain's striatum. The findings illustrate structural and functional connections that allow the brain to use reinforcement learning to make spatial decisions. Knowing how these specific pathways work together provides crucial insight into how learning occurs. It also could lead to improved treatments for Parkinson's disease.
Credit: Carnegie Mellon University
Published in the Journal of Neuroscience, the findings illustrate structural and functional connections that allow the brain to use reinforcement learning to make spatial decisions, such as the dorsolateral prefrontal (DLPFC), orbitofrontal cortex (OFC) and posterior parietal cortex (PPC). Communication between these regions is important for abilities like how a baseball player is able to estimate where to swing his bat or how a person finds a car in a large parking lot filled with similar cars.
Knowing how these specific pathways work together provides crucial insight into how learning occurs. It also could lead to improved treatments for Parkinson's disease.
"By understanding precisely how these systems communicate together, we can come up with a better understanding for how these systems operate in the healthy brain, but also start to understand how in Parkinson's disease different types of systems 'cascade,' or start with one symptom like motor dysfunction and move to another like memory or decision-making problems," said Timothy Verstynen, assistant professor of psychology and a faculty member in the Center for the Neural Basis of Cognition (CNBC) in CMU's Dietrich College of Humanities and Social Sciences.
The hope is that more knowledge of how the connectivity is related to behavior will help scientists develop therapeutic interventions that focus on strengthening potentially weakened or damaged pathways.
For the study, Verstynen and Kevin Jarbo, a Ph.D. student in psychology, used diffusion spectrum imaging and fiber technology to analyze brain images collected from 60 healthy adults. The advanced imaging techniques allowed Verstynen and Jarbo to visualize the white matter pathways from the DLPFC, OFC and PPC.
They found that the pathways from all three areas projected to similar areas within a forebrain region called striatum, a part of the basal ganglia pathways that are most commonly associated with Parkinson's disease. The patterns were consistent across all participants.
The researchers followed the structural connectivity analysis with a functional connectivity analysis by using resting state fMRI images. The results showed that the convergence zones were not only structurally connected but functionally connected as well. More importantly, the areas at the surface of the brain in all three cortical areas showed a high overlap of structure and functional connectivity.
"Our findings suggest that there may be a structural and functional network in the brain that allows us to integrate information about where we are focusing our attention in our visuospatial environment with reward and punishment signals associated with our past action choices in order to learn how to update, and hopefully improve, our future action decisions," Jarbo said.
An additional implication for this study is a deeper understanding of how reinforcement learning occurs.
"A lot of models of the reinforcement learning process assume that reward signals from the orbitofrontal cortex converge with information from other areas. These have been shown to be true for other regions of the prefrontal cortex. We are the first to show that spatial attention information from the parietal cortex may also contribute to this process," Verstynen said.
As the birthplace of artificial intelligence and cognitive psychology, Carnegie Mellon has been a leader in the study of brain and behavior for more than 50 years. The university has created some of the first cognitive tutors, helped to develop the Jeopardy-winning Watson, founded a groundbreaking doctoral program in neural computation, and completed cutting-edge work in understanding the genetics of autism. Building on its strengths in biology, computer science, psychology, statistics and engineering, CMU recently launched BrainHubSM, a global initiative that focuses on how the structure and activity of the brain give rise to complex behaviors.
The above story is based on materials provided by Carnegie Mellon University. Note: Materials may be edited for content and length.
Cite This Page:
Carnegie Mellon University. "Neuroscientists identify new way several brain areas communicate." ScienceDaily. ScienceDaily, 3 March 2015. <www.sciencedaily.com/releases/2015/03/150303183401.htm>.
Wednesday, March 4, 2015
Pharma Two B announced today that enrollment has been completed in the company's Phase IIb study of P2B001 for the treatment of early stage Parkinson's disease. One hundred and forty-nine patients enrolled in the study conducted at 29 clinical sitesthroughout the US and Israel. The results of the study, A Phase 2b, Twelve-week Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease, are anticipated in a few months.
An estimated seven to ten million people worldwide are living with Parkinson's disease (PD), a degenerative disorder of the central nervous system. Symptoms include: tremors, slowed movement (bradykinesia), rigid muscles, impaired posture and balance, loss of automatic movements, speech changes and writing changes.
The current gold standard treatment for PD is Levodopa, but long term use requires dose increases that lead to severe side effects over time including dyskinesia (uncontrolled movement) and off periods (hours of time when the patient suffers from a debilitating decrease in mobility). To delay this situation, physicians often prescribe milder drugs at the early stage of the illness. Though safer, given in low doses, these drugs are not as effective as Levodopa. Moreover, they too require dose increases over time, which also result in unwanted side effects.
"Pharma Two B's P2B001 synergistically combines two non-Levodopa drugs already individually approved for the treatment of the early stages of Parkinson's disease, in an adapted, sustained release profile. Given as low dose monotherapies, the effect of these drugs is limited. However, our preclinical studies indicate that due to their strong synergy, a low dose combination of these two drugs leads to a significant therapeutic effect, which is further enhanced when these drugs are administered in an adapted release profile enabling them to work in tandem for an extended period of time. Our observations also indicate that the emerging safety profile is very positive. We hope to reconfirm these assessments in the coming months with the final outcomes of the current Phase IIb study," said Pharma Two B CEO Dr. Nurit Livnah.
"Identifying improved solutions for PD is an important interest of the pharmaceutical industry and the medical community. We are doing our part to answer this clear and unmet need," said chairman of the board of Pharma Two B Mr. Ehud Marom. "Assuming the Phase IIb study yields positive data, we plan to immediately begin the Phase III clinical trial of P2B001, and, following the 505(b)(2) pathway, bring this important therapy to market as soon as possible. This is our goal."
About Pharma Two B
Pharma Two B is a drug discovery company in Israel, developing innovative products, with clinical and commercial added value, based on previously approved drugs. The company develops synergistic combinations of two drugs, acting in complementary biological mechanisms that enable the use of unique low doses, while maintaining high therapeutic benefit. The company also has a line of select generic products in new formulations. The company has a very experienced and dedicated management team, with both generic and innovative drug development experience. The company's chairman of the board, Mr. Ehud Marom, is credited with successfully bringing several new drugs to Phase III. He is also well known for his contribution to the successful launching of LCM and for running the global operations of the market launch of Copaxone for MS. The company's CEO is Dr. Nurit Livnah. She previously served as the V.P. of R&D at several innovative drug development companies in Israel.
SOURCE Pharma Two B