Posts tagged parkinson's disease

Tuesday, July 31, 2012

TAU researchers develop bioactive coating to “camouflage” neutral electrodes

Brain-computer interfaces are at the cutting edge for treatment of neurological and psychological disorder, including Parkinson’s, epilepsy, and depression. Among the most promising advance is deep brain stimulation (DBS) — a method in which a silicon chip implanted under the skin ejects high frequency currents that are transferred to the brain through implanted electrodes that transmit and receive the signals. These technologies require a seamless interaction between the brain and the hardware.

But there’s a catch. Identified as foreign bodies by the immune system, the brain attacks the electrodes and forms a barrier to the brain tissue, making it impossible for the electrodes to communicate with brain activity. So while the initial implantation can diminish symptoms, after a few short years or even months, the efficacy of this therapy begins to wane.

Now Aryeh Taub of Tel Aviv University's School of Psychological Sciences, along with Prof. Matti Mintz, Roni Hogri and Ari Magal of TAU’s School of Psychological Sciences and Prof. Yosi Shacham-Diamand of TAU’s School of Electrical Engineering, has developed a bioactive coating which not only “camouflages” the electrodes in the brain tissue, but actively suppresses the brain’s immune response. By using a protein called an “interleukin (IL)-1 receptor antagonist” to coat the electrodes, the multi-disciplinary team of researchers has found a potential resolution to turn a method for short-term relief into a long-term solution. This development was reported in the Journal of Biomedical Materials Research.

Limiting the immune response

To overcome the creation of the barrier between the tissue and the electrode, the researchers sought to develop a method for placing the electrode in the brain tissue while hiding the electrode from the brain’s immune defenses. Previous research groups have coated the electrodes with various proteins, says Taub, but the TAU team decided to take a different approach by using a protein that is active within the brain itself, thereby suppressing the immune reaction against the electrodes.

In the brain, the IL-1 receptor antagonist is crucial for maintaining physical stability by localizing brain damage, Taub explains. For example, if a person is hit on the head, this protein works to create scarring in specific areas instead of allowing global brain scarring. In other words, it stops the immune system from overreacting. The team’s coating, the first to be developed from this particular protein, not only integrates the electrodes into the brain tissue, but allows them to contribute to normal brain functioning.

In pre-clinical studies with animal models, the researchers found that their coated electrodes perform better than both non-coated and “naïve protein”-coated electrodes that had previously been examined. Measuring the number of damaged cells at the site of implantation, researchers found no apparent difference between the site of electrode implantation and healthy brain tissue elsewhere, Taub says. In addition, evidence suggests that the coated electrodes will be able to function for long periods of time, providing a more stable and long-term treatment option.

Restoring brain function

Approximately 30,000 people worldwide are currently using deep brain stimulation (DBS) to treat neurological or psychological conditions. And DBS is only the beginning. Taub believes that, in the future, an interface with the ability to restore behavioral or motor function lost due to tissue damage is achievable — especially with the help of their new electrode coating.

"We duplicate the function of brain tissue onto a silicon chip and transfer it back to the brain," Taub says, explaining that the electrodes will pick up brain waves and transfer these directly to the chip. "The chip then does the computation that would have been done in the damaged tissue, and feeds the information back into the brain — prompting functions that would have otherwise gotten lost."

Source: Tel Aviv University

July 24, 2012

A new class of drug developed at Northwestern University Feinberg School of Medicine shows early promise of being a one-size-fits-all therapy for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and traumatic brain injury by reducing inflammation in the brain.

Northwestern has recently been issued patents to cover this new drug class and has licensed the commercial development to a biotech company that has recently completed the first human Phase 1 clinical trial for the drug.

The drugs in this class target a particular type of brain inflammation, which is a common denominator in these neurological diseases and in traumatic brain injury and stroke. This brain inflammation, also called neuroinflammation, is increasingly believed to play a major role in the progressive damage characteristic of these chronic diseases and brain injuries.

By addressing brain inflammation, the new class of drugs — represented by MW151 and MW189 — offers an entirely different therapeutic approach to Alzheimer’s than current ones being tested to prevent the development of beta amyloid plaques in the brain. The plaques are an indicator of the disease but not a proven cause.

A new preclinical study published today in the Journal of Neuroscience, reports that when one of the new Northwestern drugs is given to a mouse genetically engineered to develop Alzheimer’s, it prevents the development of the full-blown disease. The study, from Northwestern’s Feinberg School and the University of Kentucky, identifies the optimal therapeutic time window for administering the drug, which is taken orally and easily crosses the blood-brain barrier.

"This could become part of a collection of drugs you could use to prevent the development of Alzheimer’s," said D. Martin Watterson, a professor of molecular pharmacology and biological chemistry at the Feinberg School, whose lab developed the drug. He is a coauthor of the study.

In previous animal studies, the same drug reduced the neurological damage caused by closed-head traumatic brain injury and inhibited the development of a multiple sclerosis-like disease. In these diseases as well as in Alzheimer’s, the studies show the therapy time window is critical.

Read more …

JUL 23, 2012

A new and powerful class of antioxidants could one day be a potent treatment for Parkinson’s disease, researchers report.

Dr. Bobby Thomas

A class of antioxidants called synthetic triterpenoids blocked development of Parkinson’s in an animal model that develops the disease in a handful of days, said Dr. Bobby Thomas, neuroscientist at the Medical College of Georgia at Georgia Health Sciences University and corresponding author of the study in the journal Antioxidants & Redox Signaling.

Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.

Stressors from head trauma to insecticide exposure to simple aging increase oxidative stress and the body responds with inflammation, part of its natural repair process. “This creates an environment in your brain that is not conducive for normal function,” Thomas said. “You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”

Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.

“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”

They parsed a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids the most effective on Nrf2. Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.

Both in human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids. Human dopaminergic cells are not available for research so the scientists used the human neuroblastoma cells, which are actually cancer cells that have some properties similar to neurons.

Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage. The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.

The researchers used the powerful neurotoxin MPTP to mimic Parkinson’s-like brain cell damage in a matter of days. They are now looking at the impact of synthetic triterpenoids in an animal model genetically programmed to acquire the disease more slowly, as humans do. Collaborators at Johns Hopkins School of Medicine also will be providing induced pluripotent stem cells, adult stem cells that can be coaxed into forming dopaminergic neurons, for additional drug testing.

Other collaborators include scientists at Weill Medical College of Cornell University, Johns Hopkins School of Public Health, Moscow State University, Tohoku University and the University of Pittsburgh.

Source: EarthSky

ScienceDaily (July 20, 2012) — Conditions such as Parkinson’s disease are a result of pathogenic changes to proteins. In the neurodegenerative condition of Parkinson’s disease, which is currently incurable, the alpha-synuclein protein changes and becomes pathological. Until now, there have not been any antibodies that could help to demonstrate the change in alpha-synuclein associated with the disease. An international team of experts led by Gabor G. Kovacs from the Clinical Institute of Neurology at the MedUni Vienna has now discovered a new antibody that actually possesses this ability.

"It opens up new possibilities for the development of a diagnostic test for Parkinsonism," says Kovacs, highlighting the importance of this discovery. "This new antibody will enable us to find the pathological conformation in bodily fluids such as blood or CSF." A clinical study involving around 200 patients is already underway, and the first definitive results are expected at the end of 2012. The tests being carried out in collaboration with the University Department of Neurology, led by Walter Pirker, are designed to determine the extent to which the new antibody can be used as an early diagnostic tool in order to understand the condition better and be able to treat it more effectively.

A step towards a blood test for Parkinson’s With Parkinsonism, the diseased form of alpha-synuclein, which has the same primary structure as the healthy form, undergoes an “abnormal fold.” Says Kovacs: “Until now, however, it was not possible to distinguish between the two.” The previous immunodiagnostic techniques only allowed the general presence of alpha-synuclein to be confirmed. The new, monoclonal antibody, however, which the researchers at the MedUni Vienna have developed in collaboration with the German biotech firm Roboscreen, is now able to detect a strategic part of the protein responsible for the structural changes. The results of the study have now been published in the journal Acta Neuropathologica.

Says Kovacs: “It is still not possible to say whether or not we will be able to diagnose Parkinson’s from a blood test, but this discovery certainly represents a major step in that direction.” Theoretically, it should be possible to diagnose Parkinson’s disease five to eight years before it develops.

In Austria, there are between 15,000 and 16,000 people living with Parkinson’s syndrome. Its frequency increases with age. As society becomes older, Parkinson’s disease, a degenerative condition of the brain, will become an increasingly widespread problem.

Source: Science Daily