Study suggests L-DOPA therapy for Angelman syndrome may have both benefits and unanticipated effects

Last year a clinical trial of L-DOPA — a mainstay of Parkinson’s disease therapy — was launched for Angelman syndrome, a rare intellectual disorder that shares similar motor symptoms such as tremors and difficulty with balance. The clinical trial is based on a 10-year-old case report showing benefit with the drug, but few studies since have explored the neurological justification for using L-DOPA to treat parkinsonian features in Angelman syndrome.

New research from the University of North Carolina School of Medicine, conducted in animal models of the disorder, now provides justification for this therapeutic approach. The study, published online ahead of print on Nov. 12 by the Journal of Clinical Investigation, suggests that L-DOPA could compensate for a loss of the neurochemical dopamine in the brain’s motor pathways and improve motor symptoms. However, it also indicates that the drug could add to an already increased amount of dopamine in the brain’s reward pathways and thus have unanticipated consequences on emotion and attention.

“The results were extremely surprising, because we don’t know of any other disorder where dopamine is affected one way in one brain pathway and the opposite way in another,” said Benjamin D. Philpot, PhD, associate professor of cell biology and physiology at UNC.

“If what we see in humans mirrors what we see in mice, then it does provide some optimism that L-DOPA might provide benefit for tremor,” said C.J. Malanga, MD, PhD, associate professor of neurology at UNC. “But it also raises caution that researchers might want to consider assessing other aspects of Angelman syndrome that might be affected by dopamine — not just motor symptoms but also other neuropsychiatric features.”  Malanga and Philpot are senior authors of the study.

New, Improved Mouse Model of Human Alzheimer’s May Enable Drug Discovery

Researchers at the University of Illinois at Chicago College of Medicine have developed a transgenic mouse that carries a human gene known to increase risk of Alzheimer’s 15-fold. This new mouse mimics the genetics of the human disease more closely than any of the dozen existing mouse models and may prove more useful in the development of candidate drugs to prevent or treat the disease.

The new mouse model provides new evidence for the earliest cause of Alzheimer’s, researchers report in a study to be published in the December issue of the Journal of Biological Chemistry and now available online.

The model is a cross between an existing transgenic Alzheimer’s mouse and a mouse carrying fully human apoE, a gene that in one of its three variants, apoE4, is the greatest genetic risk factor for Alzheimer’s in the human population.

(Source: tigger.uic.edu)

Human neural stem cells study offers new hope for children with fatal brain diseases

New findings demonstrate potential to treat a wide variety of disorders that affect myelin

Physician-scientists at Oregon Health & Science University Doernbecher Children’s Hospital have demonstrated for the first time that banked human neural stem cells — HuCNS-SCs, a proprietary product of StemCells Inc. — can survive and make functional myelin in mice with severe symptoms of myelin loss. Myelin is the critical fatty insulation, or sheath, surrounding new nerve fibers and is essential for normal brain function.

This is a very important finding in terms of advancing stem cell therapy to patients, the investigators report, because in most cases, patients are not diagnosed with a myelin disease until they begin to show symptoms. The research is published online in the journal Science Translational Medicine.

Myelin disorders are a common, extremely disabling, often fatal type of brain disease found in children and adults. They include cerebral palsy in children born prematurely as well as multiple sclerosis, among others.

Using advanced MRI technology, researchers at OHSU Doernbecher Children’s Hospital also recently recognized the importance of healthy brain white matter at all stages of life and showed that a major part of memory decline in aging occurs due to widespread changes in the white matter, which results in damaged myelin and progressive senility (Annals of Neurology, September 2011).

‘Disgusted’ Rats Teaching Scientists About Nausea, Work May Lead to New Cancer Treatments

Nausea is a common and distressing side effect of many drugs and treatments. Unlike vomiting, nausea is not well understood, but new research by University of Guelph scientists may soon change that.

Guelph PhD student Katharine Tuerke, neuroscience researcher Cheryl Limebeer and Prof. Linda Parker in the Department of Psychology believe they’ve found the mechanism in the brain that is responsible for the sensation of nausea – with the help of some “disgusted” rats.

Their study was published this week in Journal of Neuroscience.

“Although everyone has experienced nausea at some point, its neurobiology is poorly understood due to a lack of animal models,” said Parker, who holds the Canada Research Chair in Behavioural Neuroscience.

“We know about vomiting. The vomiting reflex is very well characterized, but the experience of nausea is something that little is known about. How is it generated? Where is it generated?”

Although rats can’t vomit, they do display a disgust reaction called gaping when re-exposed to a taste that made them feel nauseous in the past. Therefore, these gaping reactions in rats provide a model to understand brain mechanisms that produce nausea in humans.

New research proves the validity of one of the most promising approaches for combating Alzheimer’s disease (AD) with medicines that treat not just some of the symptoms, but actually stop or prevent the disease itself, scientists are reporting. The study, in the journal ACS Medicinal Chemistry Letters, also identifies a potential new oral drug that the scientists say could lead the way.

Wenhui Hu and colleagues point out that existing drugs for AD provide only “minimal” relief of memory loss and other symptoms, creating an urgent need for new medicines that actually combat the underlying destruction of brain cells. Research suggests that inflammation of nerve cells in the brain is a key part of that process. One medicine, Minozac, is in clinical trials. But Hu says Minozac still has more space to improve its efficacy. So the scientists sifted through compounds with a molecular architecture similar to Minozac in an effort to find more active substances.

The report describes success in doing so. They discovered one compound that appeared especially effective in relieving nerve inflammation and in improving learning and memory in lab mice widely used in AD research. “In general, this study not only proves that countering neuroinflammation is indeed a potential therapeutic strategy for Alzheimer’s disease, but also provides a good lead compound with efficacy comparable to donepezil [an existing AD medicine] for further oral anti-AD drug discovery and development,” the report states.