Tysabri (Natalizumab): Another Case of PML

A third case of progressive multifocal leukoencephalopathy (PML), as reported via The New York Times website:

M.S. Drug Tied to a Death
Published: March 31, 2005
By Bloomberg News

Biogen Idec and the Elan Corporation said that a third patient had developed a fatal nervous system disorder linked to the multiple sclerosis drug Tysabri, which the companies stopped selling last month.

The patient, who died in 2003, had Crohn's disease and took Tysabri in a clinical trial, said Amy Brockelman, a spokeswoman for Biogen. Tysabri won approval in November as a treatment for multiple sclerosis and the companies were studying use of the drug for other conditions.

Geoffrey C. Porges, an analyst Sanford C. Bernstein & Company, said the new information cut the chance that the companies would succeed in bringing Tysabri back to market. Biogen and Elan announced discovery of two earlier cases of the nervous system disorder.

Read the report (free registration required)

A more-detailed Bloomberg report on this case and business-world implications can be found using this link.

Joyce Carol Oates Reviews "Oblivion"

Unforgettable
A book review by Joyce Carol Oates
A new thriller from an unheralded master of suspense.
The New Yorker
04 April 2005


In the long, groping, and haphazard drama of evolution, human consciousness is a recent and precarious acquisition. Our anxiety at its precariousness has much to do with our increasing life expectancy: living longer physically, what can we expect to experience mentally? Neurological impairment is something we’re all too likely to know firsthand, and Peter Abrahams’s suspense novel “Oblivion” (William Morrow; $24.95) makes of this condition something rich and strange: an investigation into “lost time, like some dark forest in a fairy tale.” The protagonist is a forty-two-year-old Los Angeles private detective named Nick Petrov, who, at first unknowingly, suffers from a form of brain cancer (“glioblastoma multiform”) whose symptoms he attempts to rationalize or conflate with the progress of his current investigation. Unlike the morbidly compelling case studies of Oliver Sacks’s “The Man Who Mistook His Wife for a Hat” (1970), which are narrated from outside the afflicted individuals, “Oblivion” immerses us in Petrov’s assailed consciousness as he navigates his way through a Dali landscape of baffling clues, memory lapses, and visual hallucinations in an attempted reconstruction of personality that is simultaneously a search for a missing fifteen-year-old girl: “Find the girl and live."

[ ... Read the full review ... ]

Alzheimer Disease

From The Boston Globe:

Mind mystery
Alzheimer's disease appears to have multiple causes, and scientists are slowly unraveling them
By Alice Dembner, Globe Staff
March 29, 2005

A century after Alois Alzheimer identified the debilitating dementia that carries his name, scientists are still trying to determine what causes the disease in old age. Their quest takes on increasing urgency, with predictions that unless a cure is found, the number of Americans with the disease will rise from about 4.5 million now to 13 million in 2050.

Many scientists believe that Alzheimer’s results from a complex interplay of environmental factors, lifestyle choices, and genes and proteins gone haywire. But the changes in the brain that characterize the disease develop over decades and also occur in some healthy seniors, making it difficult to sort out the culprits from the bystanders.

Yet, tantalizing tidbits have surfaced in the last few weeks, including discovery of a new genetic mutation that appears to increase the risk of getting Alzheimer’s and new evidence that insulin deficiencies may contribute to deterioration of the brain.

‘‘The pieces are coming together. We’ve got the outline of the puzzle in place, and we’re beginning to see the form,’’ said Stephen Snyder, who oversees research on the causes of Alzheimer’s for the National Institute on Aging. ‘‘It’s probably five or six genes and a dozen proteins that get out of kilter,’’ said Snyder, and certainly not just the sticky clumps of proteins called beta-amyloid plaques that have received the most attention.

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

Dr. Gary Steinberg of Stanford and Moyamoya Disease

From tomorrow's New York Times, an account of a patient with moyamoya disease and the neurosurgeon who specializes in the treatment of the disease:

Out of Nowhere, a Devastating Tangle in the Brain
By DENISE GRADY
The New York Times
Published: March 29, 2005
[ ... Read the article ... ] (free registration required)~Information about Dr. Steinberg (Stanford University website)

Welcome to Numenta

numenta.

Cylert

From Reuters:

Abbott Says Withdrawing Attention Deficit Drug
24 March 2005
Health - Reuters

WASHINGTON (Reuters) - Abbott Laboratories Inc. said Thursday it was halting sales of a 30-year-old attention deficit drug that a consumer group complained was too dangerous to stay on the market.

 Abbott decided to discontinue the drug, Cylert, because of declining sales, Abbott spokeswoman Melissa Brotz said. The drug's sales this year will be less than $1 million, she said.

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

Numenta

A New Company to Focus on Artificial Intelligence
By JOHN MARKOFF
The New York Times
Published: March 24, 2005

SAN FRANCISCO, March 23 - The technologist and the marketing executive who co-founded Palm Computing in 1992 are starting a new company that plans to license software technologies based on a novel theory of how the mind works.

Jeff Hawkins and Donna Dubinsky will remain involved with what is now called PalmOne, but on Thursday they plan to announce the creation of Numenta, a technology development firm that will conduct research in an effort to extend Mr. Hawkins's theories. Those ideas were initially sketched out last year in his book "On Intelligence: How a New Understanding of the Brain Will Lead to the Creation of Truly Intelligent Machines," co-written with Sandra Blakeslee, who also writes for The New York Times .

Dileep George, a Stanford University graduate student who has worked with Mr. Hawkins in translating his theory into software, is joining the firm as a co-founder.

[ ... Read the full article ... ] (free registration required.)~Redwood Neuroscience Institute

Neuroeconomics and the Cingulate Cortex

Anatomy of Give and Take
Economic theory goes only so far in explaining why people buy, sell, save or trust. Scientists are looking inside the mind for answers.
By Robert Lee Hotz, Times Staff Writer
The Los Angeles Times
18 March 2005

HOUSTON — The two women had money in mind.

Phuong Tang, 25, wriggled into a $2.5-million brain scanner at Baylor College of Medicine. Across the hall, a technician loaded Tang's trading partner for the day — Kavita Belur, 26 — into the bore of a similar machine, like a fresh artillery shell.

The two strangers were speculators in a marketplace of the mind, locked in a mutual struggle for financial gain. Belur played an investor, Tang the trustee of an investment fund.

As the pair wavered between cooperation and betrayal, scientists recorded how their brains changed. The researchers hoped to discover the secret of trust — the human variable missing from the mathematics of modern economics.
[ ... Read the full article ... ]

More M.S. Drug Woes: Avonex and 683699

Biogen and F.D.A. Issue Drug Warning
By ANDREW POLLACK
The New York Times
Published: March 17, 2005

Biogen Idec's multiple sclerosis drug Avonex might cause severe liver damage in rare cases, the company and the Food and Drug Administration said yesterday.

The warning was another blow, though probably only a glancing one, to Biogen, which is already reeling from the halt in sales of its other multiple sclerosis drug, Tysabri, which was linked to a rare brain infection.

In a related development, GlaxoSmithKline said yesterday that the F.D.A. had ordered it to halt a trial of its multiple sclerosis drug, which works in a similar way as Tysabri.

A Glaxo spokesman said the company understood that a halt was made as a precaution in trials of all drugs in the same class as Tysabri. A spokeswoman for the F.D.A. said the agency could not comment because of confidentiality about clinical trials.

[ ... Read the full article ... ] (free registration required)

Hand Tremors

From Information Week:

IBM Unveils Mouse Adapter That Assists Hand-Tremor Sufferers
IBM has developed a computer mouse that can help hand-tremor sufferers eliminate excessive cursor movements.
By Antone Gonsalves
TechWeb News
March 14, 2005

IBM on Monday said it has developed a computer mouse that can help hand-tremor sufferers eliminate excessive cursor movements, which often prevents the elderly and others from using a computer.

[snip]

The "Assistive Mouse Adapter" sits between the mouse and computer and filters out shaking movements of the hand in a way that's similar to stabilization systems found in camcorders. The device, which is designed to work with any computer and operating system, does not require additional software and can be switched on or off. It also can be adjusted to the severity of the tremors, and can filter out unintended multiple clicking on the mouse caused by a shaking finger.

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

Post Tysabri (Natalizumab): What Choices in M.S. Treatment?

The Consumer: Exploring Choices for M.S.
By MARY DUENWALD
The New York Times
15 March 2005

[snip]

An estimated 5,000 patients who had been taking Tysabri since the Food and Drug Administration approved it in late November are now advised to see their doctors for physical examinations and to consider trying other drug treatments to keep their multiple sclerosis in check or perhaps returning to them.

Those who had been in the clinical trial will be given magnetic resonance scans and other tests to check for P.M.L.

The good news, doctors say, is that most patients who took Tysabri alone and only since November are unlikely to develop progressive multifocal leukoencephalopathy.

"If there is any connection between Tysabri and the leukoencephalopathy, that risk should have been removed by stopping the drug," said Dr. Patricia Coyle, director of the multiple sclerosis clinic at the State University of New York at Stony Brook. "Patients don't have to worry that two months or six months from now they're going to come down with P.M.L."

[snip]
[ ... Read the full article ... ] (free registration required)

The iPod of the Brain

From National Public Radio:

The iPod of the Brain
by David Malakoff 
Morning Edition
March 14, 2005

Researchers at Dartmouth College find the "iPod of the brain." They've learned that the brain's auditory cortex, the part that handles information from our ears, holds on to musical memories. So even when that perky pop song isn't on the radio, you still hear it in your head.

For the NPR audio stream, click here.

The Booming Memory Industry

My brain needs Viagra
Are memory lapses the result of stressful family lives or multi-tasking? Or maybe the simple aging process?
By JAN WONG
The Globe and Mail
Saturday, March 12, 2005 Updated at 9:26 AM EST

[snip]

Senior moments are becoming boomer moments. So what? Well, this generation is the first in history to try to beat back the mental ravages of aging. (And if we aren't the first, we think we are.)

Boomers, after all, never resigned themselves to grey hair, wrinkles and bifocals. Instead, we embrace Botox, hair dye and laser-eye surgery, even if we have to get one eye done for reading, the other for distance.

Now, we want to fight the invisible. We want to stave off the inevitable winter of the mind. We want Viagra for the brain.

"Perhaps boomers are more self-conscious, literally. They don't like to reveal imperfection," says Fergus Craik, 69, a research psychologist at the Rotman Research Institute in Toronto.

His colleague, Morris Moscovitch, says that in the 1990s, reporters would interview him for memory stories once every three years. Now, he gets a call every three months. "I was thinking it was because I was becoming more prominent, but it may be because more editors are boomers," jokes Dr. Moscovitch, 59, a professor of psychology at the University of Toronto and a Rotman senior scientist.

Indeed, the memory industry is booming. There are workshops, self-help books, flash cards, board games, video games and dietary supplements. On-line sites vie to remind forgetful customers of important dates. The hottest trend is mental-gymnastics software, even though it hasn't been shown conclusively to limber up the brain.

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

Next Week is Brain Awareness Week

Brain Awareness Week: 14-20 March 2005.

The official website for Brain Awareness Week can be found at:
http://www.dana.org/brainweek/.

Periventricular Nodular Heterotopia (PNH)

B. S. Chang, MD, J. Ly, BA, B. Appignani, MD, A. Bodell, MS, K. A. Apse, ScM, R. S. Ravenscroft, BA, V. L. Sheen, MD, PhD, M. J. Doherty, MD, D. B. Hackney, MD, M. O’Connor, PhD, A. M. Galaburda, MD and C. A. Walsh, MD, PhD. Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia. Neurology 2005; 64: 799-803.

From the Division of Neurogenetics (Drs. Chang, Sheen, and Walsh, A. Bodell, K.A. Apse, and R.S. Ravenscroft), Behavioral Neurology Unit (Drs. O’Connor and Galaburda, J. Ly), and Howard Hughes Medical Institute (Dr. Walsh, A. Bodell), Department of Neurology, and Division of Neuroradiology (Drs. Appignani and Hackney), Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, and Swedish Neuroscience Institute (Dr. Doherty), Epilepsy Center, Seattle, WA.

Address correspondence and reprint requests to Dr. B.S. Chang, Department of Neurology, Beth Israel Deaconess Medical Center, NRB 02-268B, 77 Ave. Louis Pasteur, Boston, MA 02115.

Objective: To define the behavioral profile of periventricular nodular heterotopia (PNH), a malformation of cortical development that is associated with seizures but reportedly normal intelligence, and to correlate the results with anatomic and clinical features of this disorder.

Methods: Ten consecutive subjects with PNH, all with epilepsy and at least two periventricular nodules, were studied with structural MRI and neuropsychological testing. Behavioral results were statistically analyzed for correlation with other features of PNH.

Results: Eight of 10 subjects had deficits in reading skills despite normal intelligence. Processing speed and executive function were also impaired in some subjects. More marked reading difficulties were seen in subjects with more widely distributed heterotopia. There was no correlation between reading skills and epilepsy severity or antiepileptic medication use.

Conclusion: The neuronal migration disorder of periventricular nodular heterotopia is associated with an impairment in reading skills despite the presence of normal intelligence.

Neurostimulators

An excellent newspaper report on the topic of developments in pacemakers and neurostimulators was published in The Boston Globe this week:

Pacemakers aren't just for the heart anymore
By Ken Howard Wilan
The Boston Globe
March 8, 2005

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

[snip]

Spurred by the pacemaker industry, researchers are currently testing or considering using neurostimulators to treat a host of conditions, including urinary incontinence, epilepsy, migraine headaches, Parkinson's disease tremors, erectile dysfunction, depression, back pain, poor digestion and overeating in obese patients.

''It's not just the heart which can be paced," explained Dr. Stephen Oesterle, senior vice president for medicine and technology at the Minneapolis-based medical devices company, Medtronic, which makes pacemakers. ''Every tissue in the body functions because of an electrical or chemical-electrical reaction. All of a sudden you look around the body and realize you can stimulate anything which has electricity running through it."

[snip]

Medulloblastoma

This week's issue of The New England Journal of Medicine includes several articles and editorial commentary on the topic of childhood medulloblastoma and its treatment.

Business World: Tysabri (Natalizumab) and Biogen Idec

From today's Boston Globe:

Biogen Idec's top lawyer quits amid investigation
By Jeffrey Krasner
The Boston Globe
March 10, 2005

Thomas J. Bucknum, Biogen Idec's longtime top lawyer, resigned suddenly yesterday amid an inquiry by the Securities and Exchange Commission into sales of company stock by insiders around the time the company learned that patients taking its multiple sclerosis drug Tysabri had contracted a rare infection.

Bucknum sold 89,700 shares of Biogen Idec stock on Feb. 18, the day company executives learned that two patients in a long-term trial of Tysabri had the rare disease known as PML. According to documents the company filed with the SEC, Bucknum netted about $1.9 million from the sales.

[ ... Read the full article ... ]~
Note: "PML" stands for "progressive multifocal leukoencephalopathy."

Carl Zimmer's Blog

Carl Zimmer is a very readable writer of popular science. His most recent work is a biography of Thomas Willis, entitled Soul Made Flesh. I hadn't realized, until this afternoon, what an excellent blog he writes. Now, I do. His blog, The Loom, can be found at http://www.corante.com/loom/.

Help-Seeking Behavior

From a University of Wisconsin press release:

Two brain systems regulate how we call for help - Study
08 Mar 2005

The willingness to call out in distress to get help from others appears to be regulated by two brain systems with very different responsibilities, according to a study by researchers at the University of Wisconsin-Madison.

"These findings have far-reaching implications because they help clarify how a balance of two important brain systems can influence an individual's behavior and emotional expression in times of need," says Ned Kalin, senior author on the study and chair of psychiatry at UW Medical School. "The findings suggest that how open an individual is willing to be in asking for help may depend more than we thought on how secure that individual feels at any given time in a supportive relationship."

The brain systems found to be involved were the amygdala, which is important in detecting and responding to threats, and the right prefrontal cortex, which plays a role in reaching goals and attaching to others.

The study will appear in the Proceedings of the National Academy of Sciences Online Early Edition during the week of March 7-11.

[ ... Read the full release ... ]

Tysabri (Natalizumab): An Additional Case

Rare Infection Is Confirmed in 2nd Patient on M.S. Drug
By ANDREW POLLACK
The New York Times
Published: March 4, 2005

The makers of the multiple sclerosis drug Tysabri said yesterday that a second patient who used the drug had been confirmed to be suffering from a rare but deadly brain infection. The confirmed diagnosis is likely to somewhat diminish the chances that the drug will be able to return to the market.

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

Tysabri (Natalizumab) Suspension

FOR IMMEDIATE RELEASE
P05-07
February 28, 2005
Media Inquiries: 301-827-6242
Consumer Inquiries: 888-INFO-FDA

FDA Issues Public Health Advisory on Tysabri, a New Drug for MS

The Food and Drug Administration (FDA) today issued a public health advisory to inform patients and health care providers about the suspended marketing of Tysabri (nataluzimab) while the agency and the manufacturer evaluate two serious adverse events reported with its use.

Tysabri, which received accelerated approval from FDA in November 2004, is an innovative treatment that represents a new approach to treating patients with relapsing forms of multiple sclerosis (MS).

"FDA worked with the company to make sure this information, even though preliminary, was given to physicians and patients as soon as possible and supports their decision to voluntarily suspend marketing as well as the use of the product in clinical trials. At the same time, FDA continues to believe Tysabri offers great hope to MS patients," said Dr. Steven Galson, Acting Director, FDA's Center for Drug Evaluation and Research (CDER). "Patients being treated with Tysabri should contact their physician to discuss appropriate alternative treatments while these reports are being evaluated," added Dr. Galson.

FDA received a report from Biogen Idec, the manufacturer of Tysabri, of one confirmed fatal case and one possible case of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri for MS. FDA was given preliminary information about these cases by Biogen, Idec on February 18, 2005. Details became available to FDA the next week.

PML is a rare, serious progressive neurologic disease usually occurring in immunosuppressed patients. There is no known effective treatment for PML. Although the relationship between Tysabri and PML is not known at this time, because of the serious and often fatal nature of PML, FDA concurred with the company that the drug be voluntarily withdrawn from marketing and that the use of Tysabri in clinical trials be suspended until more is known.

During the review of Tysabri for marketing approval, FDA conducted an intensive analysis of possible adverse events that might be related to effects of the drug on the immune system. No cases of PML were seen in the clinical trials. However, for any approved therapy, new and unexpected adverse events may occur that were not seen in clinical trials. In the case of Tysabri, required post-marketing studies facilitated the rapid reporting and response to this new information.

According to Biogen, Idec, outside of the approximately 3,000 patients who received the drug in clinical trials, approximately 5,000 additional patients with MS have received Tysabri through their primary physician. Because Tysabri was just recently approved, these patients have only received at most a few doses of Tysabri.

The FDA will maintain close contact with the company during the process of understanding the relationship between Tysabri and these two serious adverse events. The company is working on ways to get additional information soon about the possible risks of PML from the patients who have received Tysabri in the clinical trials.

The FDA urges health care providers and patients to report adverse event information to FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178) or by the Internet at www.fda.gov/medwatch/index.html.

For further information, the public health advisory can be found on FDA's website at http://www.fda.gov/cder/drug/advisory/natalizumab.htm.