Rogue immune cells entering the brain may contribute to the development of Parkinson's disease, say scientists.

A French study in diseased mice revealed the cells accumulating in brain tissue, and mice bred to lack them did not fall ill as quickly.

The researchers suggested that the cells could be targeted using drugs.

A UK charity said the findings, published in the Journal of Clinical Investigation, did not yet prove that this approach would work.

About 120,000 people in the UK have Parkinson's disease, a progressive brain condition which causes symptoms such as tremor and difficulty moving.

This is caused by the death of nerve cells which produce the chemical dopamine, which helps coordinate movements.

Previous research had suggested a link between inflammation in the brain and the condition, pointing the finger at one of the body's own immune responses.

The researchers from the INSERM institute in Paris looked for the presence of a particular type of immune cell called a "T-cell" in the brain tissues directly affected by Parkinson's.

They found the cells gathering both in human brain samples taken from Parkinson's patients after death, and at an earlier stage in mice bred to develop the disease.

When mice lacking these immune cells were studied, the rate of nerve cell death was significantly slower.

The researchers said that this was enough evidence to start considering the possibility of using drugs to reduce this kind of immune response in patients with Parkinson's, in the hope that this might slow the progress of the disease.

Human differences

However, a spokesman for the Parkinson's Disease Society said that the research did not exclude other causes for the illness.

"This study has shown that the Parkinson's developed at a slower rate in mice lacking specific immune cells, which suggests that these cells do play a role in the development of the condition.

"However, the study doesn't determine at what stage of the disease the inflammation occurs. Therefore, the potential for anti-inflammatory treatment is difficult to determine."

He added: "It is also important to remember that as the study was done using mice, it doesn't provide a precise model for what happens in the human brain."

BY DAVID ZIZZO
Published: December 16, 2008

Many old horses suffer muscle loss and immune deficiencies. Some old people develop tremors, difficulty with movements and other symptoms. Dianne McFarlane hopes her work might someday provide help for both.

McFarlane, assistant professor of physiological sciences at the Center for Veterinary Health Services at Oklahoma State University, has been studying degenerative diseases in old horses for almost a decade. She is investigating the similarities between Cushing’s disease in horses, also known as Pituitary Pars Intermedia Dysfunction, or PPID, and Parkinson’s disease in humans.

"We are interested in understanding the disease for the benefit of horses, but also it may provide some understanding for what goes on in humans that have degenerative diseases,” she said.

McFarlane, who is collaborating with Gary White, an OSU alumnus now with the University of Oklahoma Health Science Center, is looking at degenerative disease in baboons. Many researchers use mice and rats for studies. But to use those rodents to study Parkinson’s would require inducing a degenerative disease since it does not occur naturally, as it does in horses and baboons, McFarlane said. Animals that are higher in the animal kingdom, such as horses and baboons, are better models overall for human physiology, she said.

"The closer evolutionarily you are, the more likely the processes will be handled the same,” she said.

Still, there are many differences between human Parkinson’s disease and PPID in horses. PPID, which occurs in one-quarter of horses more than 20 years old, affects the part of the brain that controls hormone output. The horses can develop sway back, potbelly or general muscle loss. The most obvious symptom is very long hair.

Parkinson’s affects the part of the human brain that controls movement, producing movement disorders, trouble sleeping, tremors and other problems.

"We have completely different clinical signs,” she said.

However, both diseases affect the same kind of dopamine-producing neurons, and both problems appear in old age. "It does appear animals have some of the same basic factors contributing to degeneration,” she said.

McFarlane’s research has produced its "first wave of data,” which was recently published.

The research is expected to continue for at least another four years.

Rogue immune cells entering the brain may contribute to the development of Parkinson's disease, say scientists.

A French study in diseased mice revealed the cells accumulating in brain tissue, and mice bred to lack them did not fall ill as quickly.

The researchers suggested that the cells could be targeted using drugs.

A UK charity said the findings, published in the Journal of Clinical Investigation, did not yet prove that this approach would work.

About 120,000 people in the UK have Parkinson's disease, a progressive brain condition which causes symptoms such as tremor and difficulty moving.

This is caused by the death of nerve cells which produce the chemical dopamine, which helps coordinate movements.

Previous research had suggested a link between inflammation in the brain and the condition, pointing the finger at one of the body's own immune responses.

The researchers from the INSERM institute in Paris looked for the presence of a particular type of immune cell called a "T-cell" in the brain tissues directly affected by Parkinson's.

They found the cells gathering both in human brain samples taken from Parkinson's patients after death, and at an earlier stage in mice bred to develop the disease.

When mice lacking these immune cells were studied, the rate of nerve cell death was significantly slower.

The researchers said that this was enough evidence to start considering the possibility of using drugs to reduce this kind of immune response in patients with Parkinson's, in the hope that this might slow the progress of the disease.

Human differences

However, a spokesman for the Parkinson's Disease Society said that the research did not exclude other causes for the illness.

"This study has shown that the Parkinson's developed at a slower rate in mice lacking specific immune cells, which suggests that these cells do play a role in the development of the condition.

"However, the study doesn't determine at what stage of the disease the inflammation occurs. Therefore, the potential for anti-inflammatory treatment is difficult to determine."

He added: "It is also important to remember that as the study was done using mice, it doesn't provide a precise model for what happens in the human brain."

Published: 2008/12/28 00:00:09 GMT

Many individuals with Parkinson's disease are able to recall losing their sense of smell well before the onset of more commonly recognized symptoms such as tremors, impaired dexterity, speech problems, memory loss and decreased cognitive ability.

To determine if a fading sense of smell may signal Parkinson's, researchers at Northwestern Memorial Hospital and Northwestern University's Feinberg School of Medicine are participating in a national study to examine the correlation and ascertain whether smell loss presents a tool for early detection of the disease and an opportunity to delay or ultimately prevent more troublesome symptoms.
Read about:
Disease

Nearly one million people in the United States are affected by Parkinson's disease, which stems from premature aging of dopamine-producing cells in the brain, and the number is likely to grow as the population ages. By the time Parkinson's disease is detected, most individuals have already experienced a 60 to 70 percent loss of dopamine-producing cells in the brain.

"Very little is known about the early stages of this disease," says Tanya Simuni, MD, director of Northwestern's Parkinson's Disease and Movement Disorders Center and Associate Professor of Neurology at Northwestern University's Feinberg School of Medicine. "By utilizing smell testing in conjunction with other tests, we hope to develop a system that identifies the presence of Parkinson's before it develops into problematic symptoms."

Northwestern is one of 15 sites nationwide and the only center in Illinois to participate in the Parkinson's Associated Risk Study (PARS), the largest long-term study in the United States of relatives of individuals with Parkinson's disease. Evaluating 7,500 relatives for three to five years, the study draws from research demonstrating that first-degree family members such as mothers, fathers, siblings or children have a slight increase in their risk to develop the disease. As age has been recognized as the single proven risk factor for the onset of Parkinson's symptoms, the study will monitor relatives 50 years or older.

PARS study participants will be sent a scratch-and-sniff test accompanied by a brief questionnaire to be completed at home, with possible follow-up through continued questionnaires or evaluation by a local neurologist. Participants may also be contacted for more extensive testing.

"This study presents an enormous opportunity to not only better understand the initial stages of Parkinson's, but also help future generations," says Dr. Simuni. "In the future, early detection combined with neuroprotective therapy may pave the way for interventions that slow the progression or even prevent the onset of Parkinson's disease."

By: Northwestern Memorial Hospital - Fri, 12/05/2008 - 07:43

JACKSONVILLE, Fla., and ROCHESTER, Minn., Nov 17, 2008 /PRNewswire-USNewswire via COMTEX/ -- Mayo Clinic researchers have developed a method to reduce the production of alpha-synuclein in the brain. Alpha-synuclein is a protein that is believed to be central to the cause of Parkinson's disease    All patients with Parkinson's disease have abnormal accumulations of alpha-synuclein protein in the brain.

Additional audio and video resources, including excerpts from an interview with Dr. Maraganore describing the research, are available on the Mayo Clinic News Blog ( http://mcnewsblog.wordpress.com/2008/11/17/potential-new-therapy-to-stop-progression-of-parkinsons-disease).

The new method involves the delivery of RNA interference compounds directly to selected areas of the brain via injection. The RNA interference compounds silence the gene that produces alpha-synuclein, according to the Mayo researchers. The study was published this month in Molecular Neurodegeneration.

Parkinson's disease is a progressive disorder that affects nerve cells in the part of the brain that controls muscle movement. Symptoms include tremor, slowed movement and rigid muscles. At least 1 million people in the U.S. are believed to have Parkinson's disease, and 2 percent of the population can expect to develop the disease during their lifetime.

"While our research has not yet been tested on humans, we expect that these findings will lead to an effective treatment for slowing or even halting the progression of Parkinson's disease," says Demetrius Maraganore, M.D. ( http://www.mayoclinic.org/bio/10345655.html), a Mayo Clinic neurologist.

Previous studies conducted by Dr. Maraganore and Matthew Farrer, Ph.D., a Mayo Clinic neuroscientist, found that variations in the alpha-synuclein gene result in increased protein production and are sufficient to cause Parkinson's disease in some families, or otherwise increase the risk for Parkinson's disease across populations worldwide.
Drs. Maraganore and Farrer invented a method to treat Parkinson's disease by reducing alpha-synuclein expression. Mayo Clinic patented and licensed their invention to Alnylam Pharmaceuticals, Inc. Alnylam is leading the effort to commercialize the Mayo invention using Alnylam RNA interference compounds.

"For this study, we developed a lead compound of small interfering RNAs," says Heather Melrose, Ph.D., a Mayo Clinic neuroscientist and a lead author of this study. "By infusing this into the brains of mice we were able to effectively reduce the production of alpha-synuclein in the brain. The therapy produced gene silencing that lasted up to three weeks after treatment, and the mice exhibited no ill effects. These are desirable characteristics of a drug therapy ultimately intended to treat disease in humans."

"Our next step with this research is to test the therapy in mice and primates with experimental forms of Parkinson's disease and prove that we are able to stop the disease progression in those animals," says Dr. Farrer. "We are hopeful, as preliminary studies suggest this is possible."

"It is important to note that there are significant hurdles to this therapy. The compound needs to be directly delivered to the brain through a neurosurgical procedure -- it cannot be given by mouth or injection into a vein," says Dr. Maraganore. "We envision that the therapy would be delivered through Food and Drug Administration (FDA)-approved devices currently used for deep brain stimulation therapy. The deep brain stimulation would treat the existing symptoms of Parkinson's disease, while the administration of the RNA interference compounds might halt the progression of the disease."

Alpha-synuclein protein also accumulates abnormally in other brain degenerations, including multiple system atrophy (MSA) and dementia with Lewy bodies. Therefore, Mayo researchers expect that RNA interference therapy could be beneficial for patients with those conditions.

Contact: Emily Shafer
Thomas Jefferson University

(WASHINGTON, D.C.) Researchers have identified a stage during dopamine neuron differentiation that may be an ideal time to collect human embryonic stem cells for transplantation to treat Parkinson's disease, according to data presented at Neuroscience 2008, the 38th annual meeting of the Society for Neuroscience.
Lorraine Iacovitti, Ph.D., professor and interim director of the Farber Institute for Neurosciences of Thomas Jefferson University, and her research team found that neural progenitor cells that express the gene Lmx1a are committed to the midbrain dopamine neuron lineage, but still retain proliferative capacity. Because of these characteristics, the stage at which Lmx1a is expressed may be ideal for transplantation.

"Identifying the subset of developing dopamine neurons and selecting those cells at the stage appropriate for their transplantation has been challenging," said Dr. Iacovitti. "Our research demonstrates that we are now able to grow neurons and select the ones that may work as a therapy, without the use of synthetic genes. This advance represents an important leap forward in the quest to devise a viable cell replacement therapy for Parkinson's disease."

The Lmx1a-positive cells cannot be identified solely by this transcription factor. However, Dr. Iacovitti and her team also found that a large percentage of the Lmx1a-positive cells express a cell surface protein called TrkB. This protein was not expressed on any of the other cell types identified in the cell culture. With TrkB as a cell surface marker, dopamine neuron progenitor cells derived from human embryonic stem cells can be selected from a heterogenous population using magnetic-activated cell sorting (MACS) or fluorescence-activated cell sorting (FACS). Neither process alters the stem cell's genome. Dr. Iacovitti and her team are now testing the ability of these cells to counteract Parkinson's disease in animal models. They will also be adapting these procedures developed in human embryonic stem cells to adult-derived human induced-pluripotent stem cells.