Tuesday, February 28, 2006

The Three-Pound Enigma by Shannon Moffett

Received my copy of this new book today. Looks great!

It was reviewed in Sunday's Washington Post, along with two other new neuroscience books: Read the review here.

And, up in March, a book by Eric Kandel.

Good times for neuroscience books written with broad appeal!
Anthony H. Risser | |

Potassium Channel Regulation Abnormalities in Neurodegeneration

From an NIH press release:

Study Implicates Potassium Channel Mutations in Neurodegeneration and Mental Retardation

For the first time, researchers have linked mutations in a gene that regulates how potassium enters cells to a neurodegenerative disease and to another disorder that causes mental retardation and coordination problems. The findings may lead to new ways of treating a broad range of disorders, including Alzheimer's and Parkinson's diseases. The study was funded in part by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS).

"This type of gene has never before been linked to nerve cell death," says Stefan Pulst, M.D., of Cedars-Sinai Medical Center at the University of California, Los Angeles, who led the new study. The report will appear in the February 26, 2006, advance online publication of Nature Genetics.

In the study, the researchers looked for the gene that caused a neurodegenerative movement disorder called spinocerebellar ataxia in a Filipino family. This disorder typically appears in adulthood and causes loss of neurons in the brain's cerebellum, resulting in progressive loss of coordination (ataxia). Dr. Pulst and his colleagues traced the disease in this family to mutations in a gene called KCNC3. The gene codes for one of the proteins that form potassium channels — pore-like openings in the cell membrane that control the flow of potassium ions into the cell. The researchers found a different KCNC3 mutation in a previously identified French family with a disease called spinocerebellar ataxia type 13, which causes childhood-onset ataxia, cerebellar degeneration, and mild mental retardation.

The KCNC3 gene codes for a type of potassium channel that normally opens and closes very quickly. This type of channel is particularly important in "fast-bursting neurons" that fire hundreds of times per second in the brain. "Fast-bursting neurons are like building blocks — they are used in the nervous system a lot," Dr. Pulst says. Among other places, these neurons are found in the brain's substantia nigra, where they aid in motor control, and in the hippocampus, where they play a role in learning. Previous studies have found abnormalities in the number of potassium channels in Parkinson's, Alzheimer's, and Huntington's diseases. Together with the new study, these findings suggest that potassium channel abnormalities may contribute to a wide variety of neurodegenerative diseases.

[ ... Read the full press release ... ]
Anthony H. Risser | |

Sunday, February 26, 2006

Upcoming Event: San Francisco, 18 March 2006: The Universe, Weighing in at Three Pounds

Looking forward to reading a new book, The Three-Pound Enigma : The Human Brain and the Quest to Unlock Its Mysteries by Shannon Moffett.

You can attend a presentation by the author on the 18th of March 2006 (7 p.m.) at Cover to Cover Booksellers , located at 1307 Castro Street, San Francisco, CA 94114. Phone: 415-282-8080.
Anthony H. Risser | |

Friday, February 24, 2006

Parkinson Disease, Creatine, and Minocycline

From an NIH new release:

Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson’s Disease

A National Institutes of Health-sponsored clinical trial with 200 Parkinson's disease patients has shown that creatine and minocycline may warrant further consideration for study in a large trial, according to Karl Kieburtz, M.D., M.P.H., University of Rochester, who spoke today at the World Parkinson Congress on behalf of the trial investigators. Study investigators caution that while the news is encouraging, the results do not demonstrate that these agents are effective in Parkinson's disease. Before these interventions can be recommended as a treatment they must be tested in a larger trial with hundreds of patients. Study findings are available online and will be published in the March 14 issue of Neurology.


The National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) has organized a nationwide multi-center effort called NET-PD (Neuroprotection Exploratory Trials in Parkinson's Disease), a randomized, double-blind futility trial, to study compounds that may slow the clinical decline of Parkinson's disease. As the initial step in these efforts, creatine and the antibiotic minocycline were identified as agents worthy of preliminary study. Patients very early in the disease course who did not yet need medications typically used to treat their Parkinson's symptoms were included in the study.


Patients were randomly assigned to receive minocycline, 200 mg per day; creatine, 10 grams per day; or placebo. The study participants were then followed for 12 months. Researchers examined the safety and tolerability of taking these medications as well as the severity of Parkinson's. Although neither agent caused major side effects, minocycline was not as well tolerated. Both creatine and minocycline appeared to modify the disease features as measured by a decline in the clinical signs of Parkinson's disease. However, it is important to note that the study was not designed nor intended to determine whether creatine or minocycline was effective as a treatment for Parkinson's. The study was primarily designed to determine whether it would be worthwhile to invest the resources necessary to determine if creatine and minocycline are effective treatments. Studies to determine the effectiveness of a drug typically require hundreds of patients followed for many years.

Based on the initial analyses of the pilot studies, creatine and minocycline have passed the first hurdle. Additionally, the NINDS has supported a pilot study of two other compounds, Coenzyme Q10 and GPI-1485, and the investigators are currently analyzing the data. The NINDS and the consortium are already planning a large long-term study of neuroprotection in Parkinson's disease.

[ ... Read the full press release ... ]
Anthony H. Risser | |

Thursday, February 23, 2006

The Game Brain

The Wall Street Journal today has an article on the front page of its Marketplace section about Nintendo's entry to The Game Brain trend: Brain Age: Train Your Brain in Minutes a Day.

Nintendo's Brain-Training Game Targets Older Players
Ginny Parker Woods
The Wall Street Journal
23 February 2006.
Anthony H. Risser | |

Tuesday, February 21, 2006

The Healthy Brain: Cognitive and Emotional Health Project

Described in an NIH press release earlier today:

Cognitive and Emotional Health Project.

From the website:
"Three Institutes, the National Institute on Aging (NIA), the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS), have joined efforts to launch a new trans-NIH initiative, Cognitive and Emotional Health Project: The Healthy Brain. There are now about 45 million Americans over age 60 and 117 million over age 40. Current evidence indicates that a large number of them are at substantial risk for cognitive impairment from many causes as they age. The same is true for emotional disorders. While research into biological mechanisms and environmental and social effects are yielding promising results in both animal and human studies, much remains to be discovered. Advances in understanding the positive and negative changes in cognition and emotion in adulthood, and what can be done to preserve and enhance positive outcomes, is at the core of the missions of the participating Institutes. The overall goal of the "Healthy Brain Project" is to assess the state of longitudinal and epidemiological research on demographic, social and biologic determinants of cognitive and emotional health in aging adults and the pathways by which cognitive and emotional health may reciprocally influence each other. A number of activities have been undertaken to accomplish these goals."

Anthony H. Risser | |

The Game Brain

From The Washington Post:

Preventive Maintenance For the Brain
Can Exercise or Mind Games Help? A Look at the Evidence
By Alicia Ault
Special to The Washington Post
Tuesday, February 21, 2006; Page HE01

If it seems you're forgetting more as you grow older, you are. Like most other organs in the body, the brain gets smaller as we age, leading to a decline in memory, decision-making ability and verbal skills. That doesn't necessarily mean that you're on a steep downhill slide toward certain dementia, say experts. Growing evidence suggests there are steps you can take to better the odds of preserving your brainpower and protecting it against disease.

[ ... Read the full article ... ]

(The article provides a nice overview to several ongoing research studies.)
Anthony H. Risser | |

Thursday, February 16, 2006

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab) and MS

From the FDA:

February 16, 2006

Media Inquiries:
Susan Cruzan, 301-827-6242
Consumer Inquiries:

FDA Allows Clinical Studies of Tysabri (natalizumab) for Treatment of MS to Proceed

The Food and Drug Administration (FDA) is reporting that Biogen-IDEC and Elan Corporation announced yesterday that FDA removed the clinical hold on Biogen-IDEC's studies of Tysabri (natalizumab) for patients with multiple sclerosis. This will allow clinical trials to go forward. In February 2005 Biogen-IDEC had announced suspension of marketing and clinical trials after three patients developed progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain, two following treatment with natalizumab for MS, and one patient being treated for Crohn's Disease. Two of these cases were fatal.

The removal of the clinical hold allows patients with MS who were previously treated with the drug under an investigational (IND) study to resume treatment in an IND study following discussion with their physicians about the potential risks and potential benefits of treatment. Although this treatment has been shown to have benefit in patients with relapsing-remitting MS, concern about the risk of PML associated with use of Tysabri remains.

FDA has worked with Biogen-IDEC over the ensuing months to assess whether any other patients exposed to natalizumab had developed an early stage of PML, what factors might have been contributory to the three PML cases that did occur, to consider what procedures could be utilized to potentially decrease the risk of PML in the future, and how to suitably monitor patients to detect a PML infection as early as feasible.

The drug is not being placed back on the market at this time. FDA has scheduled an Advisory Committee Meeting on March 7 and 8, 2006 to discuss an application for Tysabri for use in treating patients with relapsing forms of multiple sclerosis. Aspects for discussion include the risks associated with the drug, its efficacy in the treatment of multiple sclerosis relapses and disability, its possible return to the marketplace, and its proposed risk management plan(s).

For further information, health care professionals and patients can visit FDA's website at: here.

Notice for the Peripheral and Central Nervous System Drugs Advisory Committee meeting: here.

Anthony H. Risser | |

Friday, February 10, 2006

Alzheimer’s Disease Neuroimaging Initiative (ADNI)

From an NIH press release:

Alzheimer’s Disease Neuroimaging Study Launched Nationwide by the National Institutes of Health
Dr. Maya Angelou Asks Adults Ages 55 - 90 to Join Study

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) — a project developed by the National Institutes of Health (NIH) — is seeking 800 older adults to participate in a study aimed at identifying biological markers of memory decline and Alzheimer’s disease (AD). Ultimately, scientists hope that brain and biological changes can be detected before memory decline and other symptoms appear, allowing the effectiveness of drugs to be evaluated at the earliest possible time.

The $60 million, 5-year ADNI study is the most comprehensive effort to date to identify brain and other biological changes associated with memory decline. The project was begun by the National Institute on Aging (NIA) and is supported by more than a dozen other federal agencies and private-sector companies and organizations. Investigators at 58 local study sites across the U.S. and Canada will be asking people ages 55 to 90 to become a part of this landmark research.

“We encourage people to participate in this important study because it will help us to identify needed biological markers of memory decline and Alzheimer’s disease. These biomarkers could become comparable to the cholesterol measures now used as biomarkers for heart disease,” says Susan Molchan, M.D., program director for the ADNI project at the NIA. “In addition, using what we learn from the brain scans and other tests, we hope to lessen the time and cost of testing drugs and to bring treatments to patients much sooner.”

[ ... continues ... ]
Anthony H. Risser | |

Thursday, February 09, 2006


From The New York Times:
Panel Recommends Warnings for Ritalin and Other Stimulants
Published: February 9, 2006
Filed at 4:13 p.m. ET

WASHINGTON (AP) -- Federal science advisers voted narrowly Thursday to recommend the most serious type of warning labels for Ritalin and other stimulants that are used to treat attention deficit hyperactivity disorder.

The 8-7 vote, with one abstention, by the Food and Drug Administration committee was to recommend adding ''black box'' safety warnings to ADHD drugs. Doctors prescribe the increasingly popular drugs to about 2 million children and 1 million adults a month.

The FDA isn't required to follow the recommendations of its advisory committees but typically does.

[ ... Read the full article ... ]
Anthony H. Risser | |

Wednesday, February 01, 2006

Abstract of the Day: Alzheimer Disease Drug Treatments

Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25; (1): CD005593.

BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. The most that these drugs could achieve is to modify the manifestations of Alzheimer's disease. Cochrane reviews of each ChEI for Alzheimer's disease have been completed (Birks 2005, Birks 2005b and Loy 2005). Despite the evidence from the clinical studies and the intervening clinical experience the debate on whether ChEIs are effective continues. OBJECTIVES: To assess the effects of donepezil, galantamine and rivastigmine in people with mild, moderate or severe dementia due to Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched using the terms 'donepezil', 'E2020' , 'Aricept' , galanthamin* galantamin* reminyl, rivastigmine, exelon, "ENA 713" and ENA-713 on 12 June 2005. This Register contains up-to-date records of all major health care databases and many ongoing trial databases. SELECTION CRITERIA: All unconfounded, blinded, randomized trials in which treatment with a ChEI was compared with placebo or another ChEI for patients with mild, moderate or severe dementia due to Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer (JSB), pooled where appropriate and possible, and the pooled treatment effects, or the risks and benefits of treatment estimated. MAIN RESULTS: The results of 13 randomized, double blind, placebo controlled trials demonstrate that treatment for periods of 6 months and one year, with donepezil, galantamine or rivastigmine at the recommended dose for people with mild, moderate or severe dementia due to Alzheimer's disease produced improvements in cognitive function, on average -2.7 points (95%CI -3.0 to -2.3), in the midrange of the 70 point ADAS-Cog Scale. Study clinicians blind to other measures rated global clinical state more positively in treated patients. Benefits of treatment were also seen on measures of activities of daily living and behaviour. None of these treatment effects are large.There is nothing to suggest the effects are less for patients with severe dementia or mild dementia, although there is very little evidence for other than mild to moderate dementia.More patients leave ChEI treatment groups, approximately 29 %, on account of adverse events than leave the placebo groups (18%).There is evidence of more adverse events in total in the patients treated with a ChEI than with placebo. Although many types of adverse event were reported, nausea, vomiting, diarrhoea, were significantly more frequent in the ChEI groups than in placebo.There are four studies, all supported by one of the pharmaceutical companies, in which two ChEIs were compared, two studies of donepezil compared with galantamine, and two of donepezil compared with rivastigmine. In three studies the patients were not blinded to treatment, only the fourth, DON vs RIV/Bullock is double blind. Two of the studies provide little evidence, they are of 12 weeks duration, which is barely long enough to complete the drug titration. There is no evidence from DON vs GAL/Wilcock of a treatment difference between donepezil and galantamine at 52 weeks for cognition, activities of daily living, the numbers who leave the trial before the end of treatment, the number who suffer any adverse event, or any specific adverse event.There is no evidence from DON vs RIV/Bullock of a difference between donepezil and rivastigmine for cognitive function, activities of daily living and behavioural disturbance at two years. Fewer patients suffer adverse events on donepezil than rivastigmine. AUTHORS' CONCLUSIONS: The three cholinesterase inhibitors are efficacious for mild to moderate Alzheimer's disease. It is not possible to identify those who will respond to treatment prior to treatment. There is no evidence that treatment with a ChEI is not cost effective. Despite the slight variations in the mode of action of the three cholinesterase inhibitors there is no evidence of any differences between them with respect to efficacy. There appears to be less adverse effects associated with donepezil compared with rivastigmine. It may be that galantamine and rivastigmine match donepezil in tolerability if a careful and gradual titration routine over more than three months is used. Titration with donepezil is more straightforward and the lower dose may be worth consideration.

PMID: 16437532 [PubMed - in process]

Anthony H. Risser | |