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joi, 15 decembrie 2011

New Drug That Improves Memory And Prevents Brain Damage In Mice May Prevent Alzheimer's Disease Progression

Main Category: Alzheimer's / Dementia
Also Included In: Parkinson's Disease;  Huntingtons Disease;  Stroke
Article Date: 15 Dec 2011 - 7:00 PST

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A new drug candidate may be the first capable of halting the devastating mental decline of Alzheimer's disease, based on the findings of a study published in PLoS one.

When given to mice with Alzheimer's, the drug, known as J147, improved memory and prevented brain damage caused by the disease. The new compound, developed by scientists at the Salk Institute for Biological Studies, could be tested for treatment of the disease in humans in the near future.

"J147 enhances memory in both normal and Alzheimer's mice and also protects the brain from the loss of synaptic connections," says David Schubert, the head of Salk's Cellular Neurobiology Laboratory, whose team developed the new drug. "No drugs on the market for Alzheimer's have both of these properties."

Although it is yet unknown whether the compound will prove safe and effective in humans, the Salk researchers' say their results suggest the drug may hold potential for treatment of people with Alzheimer's.

As many as 5.4 million Americans suffer from Alzheimer's, according to the National Institutes of Health. More than 16 million will have the disease by 2050, according to Alzheimer's Association estimates, resulting in medical costs of over $1 trillion per year.

The disease causes a steady, irreversible decline in brain function, erasing a person's memory and ability to think clearly until they are unable to perform simple tasks such as eating and talking, and it is ultimately fatal. Alzheimer's is linked to aging and typically appears after age 60, although a small percentage of families carry a genetic risk for earlier onset. Among the top ten causes of death, Alzheimer's is the only one without a way to prevent, cure or slow disease progression.

Scientists are unclear what causes Alzheimer's, which appears to emerge from a complex mix of genetics, environment and lifestyle factors. So far, the drugs developed to treat the disease, such as Aricept, Razadyne and Exelon, only produce fleeting memory improvements and do nothing to slow the overall course of the disease.

To find a new type of drug, Schubert and his colleagues bucked the trend within the pharmaceutical industry of focusing exclusively on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease. To date, Schubert says, all amyloid-based drugs have failed in clinical trials.

Instead, the Salk team developed methods for using living neurons grown in laboratory dishes to test whether or not new synthetic compounds were effective at protecting the brain cells against several pathologies associated with brain aging. Based on the test results from each chemical iteration of the lead compound, which was originally developed for treatment of stroke and traumatic brain injury, they were able to alter its chemical structure to make a much more potent Alzheimer's drug.

"Alzheimer's is a complex disease, but most drug development in the pharmaceutical world has focused on a single aspect of the disease - the amyloid pathway," says Marguerite Prior, a research associate in Schubert's lab, who led the project along with Qi Chen, a former Salk postdoctoral researcher. "In contrast, by testing these compounds in living cell cultures, we can determine what they do against a range of age-related problems and select the best candidate that addresses multiple aspects of the disease, not just one."

With a promising compound in hand, the researchers shifted to testing J147 as an oral medication in mice. Working with Amanda Roberts, a professor of molecular neurosciences at The Scripps Research Institute, they conducted a range of behavioral tests that showed that the drug improved memory in normal rodents.

The Salk researchers went on to show that it prevented cognitive decline in animals with Alzheimer's and that mice and rats treated with the drug produced more of a protein called brain-derived neurotrophic factor (BDNF), a molecule that protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation.

Because of the broad ability of J147 to protect nerve cells, the researchers believe that it may also be effective for treating other neurological disorders, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS), as well as stroke.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alzheimer's / dementia section for the latest news on this subject. The research was funded by the Fritz B. Burns Foundation, the National Institutes of Health, the Bundy Foundation and the Alzheimer's Association.
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Study To See If Walking And/Or Memory Training May Prevent Memory Problems In People With Parkinson's Disease

Main Category: Parkinson's Disease
Also Included In: Stroke;  Rehabilitation / Physical Therapy;  Clinical Trials / Drug Trials
Article Date: 15 Dec 2011 - 0:00 PST

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Researchers from the University of Maryland School of Medicine and the Baltimore VA Medical Center have launched a study of exercise and computerized memory training to see if those activities may help people with Parkinson's disease prevent memory changes. The type of memory that will be examined is known as "executive function;" it allows people to take in information and use it in a new way. Many Parkinson's patients develop problems with executive function, which can prevent them from working and may eventually require a caregiver to take over more of the complex cognitive tasks of daily living.

"Studies of normal aging show that memory and executive function can be improved with exercise, such as walking several days a week," explains Karen Anderson, M.D., principal investigator and an assistant professor of neurology and psychiatry at the University of Maryland School of Medicine. Dr. Anderson is also a neuro-psychiatrist at the Maryland Parkinson's Disease and Movement Disorders Center at the University of Maryland Medical Center and a clinician in mental health at the Baltimore VA Medical Center.

She adds, "We want to see if exercise can slow or reverse some of these memory changes in Parkinson's patients. We will also investigate whether a computer game designed to improve executive function may make a difference as well. The other question is, what happens when you put the two interventions together - if there is memory improvement, will it be even better than with one of the interventions? Or is it more efficient to do just one or the other? We really do not know."

The researchers, who received funding through a VA Merit Award, plan to enroll about 90 patients who will be divided randomly into three groups: exercisers walking on a treadmill, memory game players and those doing both exercise and memory games. Participants in each group will receive a memory assessment at the beginning of the study. They will come in three times a week for their training for three months and will be then be tested again. Three months after that, the researchers will test the participants again to see if there may be longer term benefits to the training.

With both the treadmill walking and the memory game, the exercise or video game will become more challenging as the participant improves. The memory training works like a video game with players advancing to a higher level of difficulty. For the exercisers, trainers may increase the speed or slope of the treadmill to make it more aerobically challenging.

"This new study builds on our experience from a previous study of exercise for gait and mobility in Parkinson's disease. Since both motor function and cognitive function are important for mobility and performance of daily activities, this new study will investigate the individual and combined effects of treadmill training and cognitive training," explains Lisa Shulman, M.D., co-investigator and professor of neurology at the University of Maryland School of Medicine.

"Parkinson's patients are eager to know if there is anything they can do to give them greater control over their condition. Mobility and memory are the two key components to preserve independence. If these treatment strategies are found to be effective, we will learn important new approaches to delaying disability," says Dr. Shulman who is co-director of the Maryland Parkinson's Disease and Movement Disorders Center.

The treadmill training will take place at the Baltimore VA Medical Center in the Maryland Exercise and Robotics Center of Excellence, a gym facility with specialized equipment for people with physical limitations or balance issues. For safety, participants will wear a safety harness while walking on the treadmill. Experienced exercise physiologists will supervise each training session.

The computerized memory training game will take place both at the VA and University of Maryland School of Medicine.

"This study shows the commitment of our University of Maryland faculty to exploring new approaches, such as exercise and memory training, to help patients with illnesses such as Parkinson's disease around the world," says E. Albert Reece, M.D., Ph.D., M.B.A, vice president for medical affairs, University of Maryland, and dean, University of Maryland School of Medicine.

The Maryland researchers expanded the exercise studies to Parkinson's patients after first finding success with treadmill training for stroke patients. This research, also conducted at the University of Maryland School of Medicine and the VA Maryland Health Care System, found that regular exercise on a treadmill can improve stroke patients' walking ability even years after they've had a stroke.

Co-investigator Richard Macko, M.D., says, "With stroke patients, we have seen that the consistent, repetitive motion of walking may help the brain to develop new connections to compensate for the damaged ones. This new Parkinson's study takes the concept of exercise training for neurology patients in a new direction. We will be interested to see if this consistent training will produce benefits to memory." Dr. Macko is director of the Maryland Exercise and Robotics Center of Excellence at the VA Maryland Health Care System and professor of neurology at the University of Maryland School of Medicine.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our parkinson's disease section for the latest news on this subject. Parkinson's disease affects about one million people in the United States and Canada. Most people begin to develop symptoms in their late 50s or early 60s, although it can occur in younger people.
Parkinson's disease affects the brain's ability to produce dopamine, the neurotransmitter involved in the communication between the brain cells for motor control. Physical symptoms include tremor, muscle rigidity and slowness of movement. There are also non-motor symptoms such as changes in memory ability, sleep disturbances and depressed mood.
Parkinson's patients interested in enrolling in the exercise and memory study should call 443-827-0677.
University of Maryland Medical Center Please use one of the following formats to cite this article in your essay, paper or report:

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University of Maryland Medical Center. "Study To See If Walking And/Or Memory Training May Prevent Memory Problems In People With Parkinson's Disease." Medical News Today. MediLexicon, Intl., 15 Dec. 2011. Web.
15 Dec. 2011. APA
University of Maryland Medical Center. (2011, December 15). "Study To See If Walking And/Or Memory Training May Prevent Memory Problems In People With Parkinson's Disease." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/239162.php.

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joi, 8 decembrie 2011

Identifying Interventions To Delay Or Prevent Breast Cancer Recurrences After Tamoxifen

Main Category: Breast Cancer
Article Date: 08 Dec 2011 - 1:00 PST

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An international research team led by Georgetown Lombardi Comprehensive Cancer Center has found biological differences in hormone-receptor positive breast cancer that are linked to the timing of recurrence despite endocrine therapy.

They say their findings, presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, may help oncologists find ways to individualize systemic therapy to delay or prevent recurrences, and to avoid excessive treatment of patients who will never recur.

"We found that, at the time of diagnosis, there are clear biological differences within the supposedly uniform group of hormone receptor positive breast cancers, and these differences distinguish subtypes relative to the time at which they recur," says Minetta Liu, M.D., director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center.

"We need to exploit these differences and use our data to figure out what drives a tumor to never metastasize. Then we will try to manipulate the cancers that are programmed to recur to act like that of the non-recurrences," she says.

Tamoxifen is credited with saving the lives of thousands of women with estrogen receptor-positive (ER+) breast cancer, which accounts for two-thirds of all diagnoses of invasive breast cancer in the United States. As the world's leading breast cancer treatment and prevention drug, tamoxifen can stave off cancer recurrences for more than 10 years in some patients, but for others, the cancer returns much earlier.

To determine why some ER+ cancers treated with tamoxifen recur earlier rather than later, if at all, Liu and her Georgetown team collaborated with researchers at the University of Edinburgh and with engineers at Virginia Tech.

The Scottish collaborators shared high quality tumor biopsies collected from patients with different stages of breast cancer before they had started tamoxifen therapy. Critical clinical information was available to determine whether or not patients developed metastatic disease, and when the recurrence (if any) was found. The samples were processed and analyzed at Georgetown. Then scientists at Virginia Tech examined the gene expression patterns generated from the tumor biopsies relative to the known clinical outcomes to develop a predictive model of early, late or no disease recurrence.

The final analysis revealed distinct patterns in cancers that recurred early (up to three years from diagnosis) or late (more than ten years from diagnosis). Liu says that some of the genes that were identified were "expected and reassuring," but others were "unexpected and novel." Work is ongoing to validate selected genes as biological drivers of metastasis.

"Endocrine therapy and chemotherapy are not without toxicity," Liu says. "The ability to predict which patients will recur early in their treatment course can lead to more appropriate recommendations for adjuvant chemotherapy. It might also identify those women who would benefit most from studies using investigational agents to enhance the effects of tamoxifen or aromatase inhibitors."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. The authors declare no conflicts of interest.
The U.S. Department of Defense and Breakthrough Breast Cancer (Scotland) funded the research.
Georgetown University Medical Center Please use one of the following formats to cite this article in your essay, paper or report:

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8 Dec. 2011. APA

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View the original article here