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November 01, 2005

Obesity: The Search for a Skinny Pill

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Posted by Zack Lynch

The latest data from the Center of Health Statistics show that 30% of U.S. adults over 21 are obese. The percentage of young people who are overweight has more than tripled since 1980. And among children and teens, 16% are considered overweight.

Obesity is not just a cosmetic problem. It causes impaired mobility, decreased heat tolerance, excessive sweating and skin folds leading to skin lesions and infections. It is also associated with more serious debilitating and deadly conditions. Among these are hypertension, high lipid levels, cardiovascular illness including heart attack and stroke, type 2 diabetes leading to blindness, kidney failure, and limb amputations, gall bladder disease, osteoarthritis, sleep apnea and respiratory problems, as well as some cancers, including breast, colon and endometrial cancer. In short, it is a major health problem with a real effect on life-expectancy.
 This article in Neurotech Insights covers mechanism of obesity, treatment development strategies, and clinical trial pipelines.

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Arena’s Obesity Drug Scores in Phase II Trial

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Posted by Zack Lynch

Arena Pharmaceuticals (ARNA) is a mid-size San Diego biotech company focused on G-coupled protein receptors (GPCR's). GPCR's are a class of receptor molecules that mediate the majority of cell to cell communication in the human body. These receptors are also drug targets of choice and estimates are that better than 50% of the drugs on the market today are aimed at GPCR's.

The company was founded in 1997 based on a novel idea called Constitutively Activated Receptor Technology or CART in conjunction with a readout agent called a melanophore. The CART technology enabled company scientists to measure receptor activity and changes to that activity caused by an experimental compound, without knowing the natural ligand of that receptor. Since the natural ligands for most GPCR's were unknown at the time, and a significant number still are, it opened the door for new discoveries. Such capabilities did not go unnoticed and the small company soon had big pharma partners, substantial amounts of cash and was able to go public a year and a half later….

For the full interview with Arena's CEO see the October 31st edition of Neurotech Insights

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September 08, 2005

Using Brain Scans to Figure Out What Women Want

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Posted by Zack Lynch

What will they think of next? MIT's Technology Review reports on the following:

"Drug companies make $2.5 billion a year selling Viagra, Cialis and Levitra to help men enjoy sex. Since more women suffer from sexual dysfunction than men, developing a drug that could double those sales would seem to be a no-brainer. Yet the pharmaceutical industry has failed women miserably -- there isn't a single sexual dysfunction drug on the market that can help them. Pfizer Inc. last year abandoned an eight-year Viagra study involving 3,000 women, conceding that its famous blue pill only works for men.

While Pfizer and other pharmaceutical titans have abandoned the pursuit of a Viagra for females as too complicated, a growing number of university researchers are reporting progress with the help of brain scanners and other technology.

Yes, they're watching women's brains while they have orgasms. And they're coming to some interesting conclusions."

While Big Phama may have given up on FSD, several smaller companies are making progress, including: Nastech Pharmaceutical (apomorphine HCI) in Phase II; Solvay Pharmaceuticals (Estratest) in Phase II; BioSante Pharmaceuticals (LibiGel) completed Phase II; and Palatin Technologies (PT-141) in Phase II.

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August 22, 2005

Eyetech Bought by OSI (Neuropharma M&A)

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Posted by Zack Lynch

From the associated press:

"Shares of Eyetech soared this morning after OSI Pharmaceuticals announced it would buy the drug developer for $935 million. Eyetech developed and co-markets Macugen for macular degeneration. OSI will pay $20 per share, a 43 percent premium. Seventy-five percent of the purchase price will be paid in cash, the rest in stock. Analysts say that the move will expand OSI beyond its trademark cancer treatments, but OSI's shares tumbled about 10 percent on the news.

"The acquisition of Eyetech represents the rare opportunity to combine two inherently strong growth stories and create a dynamic new entity with real strength. The combination of OSI and Eyetech will create a substantial biopharmaceutical company with over $600 million of projected revenues in 2006 and strong growth prospects for the future," commented Colin Goddard, PhD, CEO of OSI Pharmaceuticals."

Looks like OSI understands just how big a market opportunity the neuropharmaceutical sector represents.

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June 29, 2005

Insomnia Science Discussed at NIH

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Posted by Zack Lynch

From Psychscape:

A recent consensus panel was convened at NIH to discusses the specific challenges facing insomnia research and recommended a variety of studies to help clarify the disorder's underlying mechanisms, natural history, the interaction between insomnia and other conditions, and the comparative risks and benefits of various therapies. The panel released its findings last week, following two days of expert presentations and panel deliberations.

Insomnia is the most common sleep complaint reported by women and men across all stages of adulthood, and for many, the problem is not episodic but chronic. Insomnia is both a symptom of certain conditions as well as a disorder with complex and, likely, multiple causes. Chronic insomnia is associated with a wide range of adverse effects, including depression; alcohol and drug abuse; difficulties with concentration and memory; and various cardiovascular, pulmonary, and gastrointestinal disorders.

The panel expressed concern that many of the drugs now used to treat insomnia, such as antidepressants and antihistamines, have not been approved for this indication and their efficacy in treating chronic insomnia has not been proven. Even those medications that have been approved for insomnia are approved only for short-term use, leaving chronic sufferers with few proven options. The panel noted that newer benzodiazepine receptor agonist medications have been developed that have fewer and less severe adverse effects than other medications, and show promise for long-term use, but this requires further evaluation. The panel also expressed concern that many insomnia sufferers self-medicate with alcohol, despite the numerous risks involved and the clear evidence that alcohol actually has a negative overall effect on the quality of sleep.

Interestingly, there is a body of research that indicates that behavioral methods such as relaxation training can be effective to treat insomnia when combined with cognitive therapies specifically targeted at anxiety-producing beliefs and erroneous beliefs about sleep and sleep loss. Moreover, this approach is unlikely to carry adverse side effects, and its benefits may be longer lasting than pharmacological interventions. The down-side to this intervention is that there are few practitioners trained in these therapies.

The live webcast was sponsored by the Office of Medical Applications of Research (OMAR) and the National Institute of Mental Health. Cosponsors included the National Center for Complementary and Alternative Medicine, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the National Institute of Nursing Research, the National Institute on Aging, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the Office of Research on Women's Health, and the U.S. Food and Drug Administration.

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April 05, 2005

Molecules for the Mind - Tapping Into the Booming Neuropharma Market (April 19th)

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Posted by Zack Lynch

What challenges do entrepreneurs face in order to turn a research concept into a successful company with viable treatments?

Find out on April 19th at this month's MIT/Stanford Venture Lab, where Jeffrey Ostrove, CEO of Ceregene, discusses how they overcame scientific challenges, negotiated licensing deals, and obtained $32 million in venture financing, in their quest to develop the first gene therapy treatment for neurological disorders.

Panelist adding their perspectives to the discussion include: David Mack, Director of early life science investments at Alta Partners, David Summa, President and CEO of Acumen Pharmaceuticals, Thorsten Melcher, Vice President of Discovery at Saegis Pharmaceuticals, and Frank Eeckman, Managing Editor of Centient Biotech Investor will also be sharing their thoughts on critical pitfalls and opportunities in neuropharmaceutical discovery and development.

Please join me, as I moderate this panel of experts through a discussion that will help entrepreneurs, researchers, venture investors and the general public learn how they too can tap into the booming neurotechnology market.

Event Details:
Date: Tuesday, April 19, 2005
Time: 6:00 PM - Reception, Arbuckle Lounge, Stanford Business School
7:00 PM - Presentation & Discussion, Bishop Auditorium, SBS
Directions: (Click here)
Registration: (click here)

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March 09, 2005

Neuropharmaceutical Approval Process - The FDA's Slow Road

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Posted by Zack Lynch

Regulation of neuropharmaceuticals and neurodevices fall under two different centers within the FDA. Pharmaceuticals are overseen by the Center for Drug Evaluation and Research (CDER), while devices are overseen by the Center for Devices and Radiological Health (CDRH).

The Current FDA Neuropharmaceutical Approval Process

Manufacturers who intend to market a new drug must go through a very complex and expensive process. Bringing a new drug to market can take a drug maker 10-15 years at a cost of over $800 million. There are several steps involved in obtaining FDA approval for a new drug (which is getting more difficult)

The first step is to submit an Investigational New Drug (IND) application to the FDA that contains preclinical information: animal pharmacology and toxicology data to determine if the product is safe for initial testing in humans; information on the chemistry, manufacturing & controls to determine if company can produce drug consistently; and the clinical protocols to determine if the methods for conducting the study will cause harm to human test subjects.

When the FDA has cleared the IND application, the drug manufacturer can conduct clinical trials for the drug on patients living within the United States. Clinical trials have three phases:

Phase I: Study of drug in 20 to 80 healthy human volunteers for up to one year to provide information on the drug's toxicity and potential side effects.

Phase II: This type of study is conducted on patients with the targeted disease that the drug is intended to treat over two years to test the drug's safety and efficacy.

Phase III: This is the most comprehensive of the investigational studies focusing on a large number of patients (typically several hundred to several thousand) for approximately two to four years, depending on the drug and the patient population.

Once the manufacturer has successfully completed three phases of clinical studies on an investigational drug, they submit the information as part of a New Drug Application (NDA). Along with the clinical trial results, the manufacturer must also provide: the technical instructions for using the product and the promotional materials used to market the drug to consumers to ensure the claims are appropriate; a manufacturing summary that details of how the drug will be prepared and manufactured and what controls are in place to guarantee a consistent product; non-clinical Information on how the drug should be administered, to whom and at what doses; and a risk/benefit analysis.

The drug maker's submission is reviewed by the FDA and if the drug is granted NDA approval, the FDA may require that the drug maker engage in a phase IV clinical study, which may be larger and longer term than the phase III trial. The phase IV study is designed to monitor the ongoing safety and efficacy of the drug.

Are we ready for FasterCures yet? Check out this suggested process for accelerating the approval process. Indeed, recent events have begun to make many question the concept of accelerating the process at all. Watch out for Pharma's horizontal future.

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February 28, 2005

Multiple Sclerosis Drug Tysabri Pulled Off Market

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Posted by Zack Lynch

Biogen Idec and Elan announced Monday they have voluntarily withdrawn Tysabri, a drug used to treat multiple sclerosis, after one patient died and another developed a serious disease of the central nervous system after taking it in combination with Avonex for more than two years.

Tysabri was approved last November by the FDA after several years of clinical trials and is the first humanized monoclonal antibody approved for the treatment of MS. It acts by inhibiting adhesion molecules (docking devices) on the surface of immune cells lymphocytes.

Stocks of both companies were pounded in early trading today down 40% (BIIB) and 70% (ELN), respectively. The companies said in a news release that they have suspended supplying and marketing the drug and advised doctors to suspend prescribing the medication. The companies also have stopped using the drug in clinical trials.

MS affects over 400,000 Americans and over 2 million individuals worldwide.

CORRECTION/UPDATE 03/07: Due to an error in an Associated Press story on Friday, this blog incorrectly stated a second patient taking Tysabri had died as a result of PML. One patient died, while the second patient was confirmed to have contracted progressive multifocal leukoencephalopath.

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February 05, 2005

The Chemical Architecture of the Human Mind by Tom Ray

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Posted by Zack Lynch

Last year, in a six part series, interdisciplinary neuroecoscientist Tom Ray shared a simplified version of his work on using psychedelics to probe and map the receptor space of the human mind here on Brain Waves. The following is a more technical overview of his brilliant work.

The Chemical Architecture of the Human Mind: Probing Receptor Space with Psychedelics
by Tom Ray

Nineteen psychedelics (2C-B, 2C-B-fly, DOB, DOI, DOM, 2C-E, 2C-T-2, ALEPH-2, Mescaline, MEM, MDA, MDMA, DMT, 5-MeO-DMT, 5-MeO-MIPT, DIPT, 5-MeO-DIPT, DPT, Psilocin) and three controls (lisuride 6-fluoro-DMT, 4C-T-2) have each been screened against the full panel of over one hundred receptors, transporters and ion channels by the National Institute of Mental Health Psychoactive Drug Screening Program (NIMH-PDSP), providing the first comprehensive view of how these compounds interact with the human receptome.

Each individual psychedelic causes a unique spectrum of subjective effects. DIPT causes auditory distortion. 5-MeO-DIPT enhances orgasm in males but not females. MDMA provokes empathy. TMA provokes anger. Mescaline provokes an appreciation of beauty. 2C-B causes tactile, gustatory and sexual enhancement. 2C-E provokes rich fantasy and introspection. Taken collectively, these compounds provide a rich set of tools for probing and revealing the chemical organization of the human brain and the mind that emerges from it.

The project aims to understand the mechanisms underlying the qualitative diversity of actions of psychedelics, by locating each drug in an abstract " receptor space", a coordinate system with one axis for each receptor. Drugs shift the balance of activity of the brain away from the origin, by a vector representing the profile of binding affinities at different receptors. Drugs perturb the system through increasing or decreasing transmission or transmitter levels, or up or down regulating receptor populations.

In a brain-centered reference frame, the origin is based on absolute levels of activity at each receptor population. The state of the brain is constantly on the move, regardless of medication. We can think of it as a complex dynamical system, in which the trajectory follows high-dimensional orbits, and switches among many "attractors", where the attractors represent the major emotional states and moods, and whatever mental phenomena the chemical systems are mediating.

In this dynamic reference frame, drugs will create a perturbation along the binding vector, thereby pushing the system into a new attractor. We want to understand how patterns of activity at receptor populations associate with mental phenomena. We want to get to know the pharmacology of the attractors. By correlating the subjective effects of a diverse selection of psychedelic drugs with the position of the drugs in "receptor space", we can begin to map the chemical organization of the human mind.

The current project is charting the distribution of psychedelics in "receptor space". In future work, new human data will be needed, using subjective questionnaires and brain imaging, as in the work of Vollenweider. For human work, compounds will be carefully chosen to represent distinct regions of "receptor space", or distinct subjective effects.

The goal of mapping "receptor space" is to chart the relationships between complex alterations in chemical signaling, and resulting changes in neural activity and mental states. This empirical knowledge can form a foundation for the development of a theory of the chemistry of mind, and provide a more rational basis for the development of chemical treatments for mental disorders. The understanding of the chemistry of consciousness is the ultimate goal of this research.

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October 04, 2004

2004 Nobel in Medicine: Smelling Success

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Posted by Zack Lynch

The 2004 Nobel Prize in Medicine was awarded yesterday to Richard Axel and Linda Buck for their work on the neurobiology of smell. While previous Nobel's have been awarded to scientists who discovered how sight (1981) and sound (1961) are perceived, figuring out the human nose took longer because it required modern DNA technology to find the microscopic cells and track the proteins.

As Nature described, "Together they discovered a large gene family, comprised of some 1,000 different genes (some 3 percent of our genes) that give rise to an equivalent number of olfactory receptor types. These receptors are located on the olfactory receptor cells, which occupy a small area in the upper part of the nasal epithelium and detect the inhaled odorant molecules. They also worked out the neural circuitry that passes the signal on to the higher parts of the brain, which deal with more complex matters, such as automatic recall of a childhood memory or, more pragmatically, deciding whether to discard a whiffy meal or move closer to a potential mate."

Understanding the neurobiology of our senses have recently lead to a new set of neuropharmaceutical companies focused treating age-related sensory decline and sensory loss. Some of the leading sensoceutical companies include Eyetech Pharmaceuticals, Sound Pharmaceuticals and Pain Therapeutics.

I wonder when they'll figure out how to make everything taste good too.

Update 10/08: In 2000, Sentigen Holdings Corp. licensed the right to the olfactory discoveries from Columbia University. Patents are pending. (source: WSJ 10/04)

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September 27, 2004

ADHD - NeuroImaging Used to Understand $77B problem

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Posted by Zack Lynch

Do you ever lose focus after working for several hours on a project? Are there times when you just can't seem to concentrate anymore? If you answered yes to these questions then you are probably normal. But what is normal? And for that matter what is attention deficit "hyperactivity" disorder, ADHD? According to the DSM, there are sixteen behavioral differences between the two groups.

In a recent Harvard study claimed that ADHD costs Americans suffering from the condition about $77 billion in lost income a year, more than the total costs of drug abuse or depression. Usually considered a childhood disorder, ADHD affects about 8 million U.S. adults and is linked to job loss, lower income, higher divorce rates and more driving accidents, said Dr. Joseph Biederman, professor of psychiatry at Harvard Medical School.

To help understand how the current set of attention focusing cogniceuticals impact normal brains versus those with ADHD, the NIMH recently approved a study that would give normal children and children with ADHD dextromethylphenadate and use neuroimaging techniques to see if there is a different response.

Since there are currently no biomarkers or neuroimaging tests that define ADHD from a neurological perspective, some argue that it doesn't exist. This new trial would add magnetic resonance images to map any differences in brain activation patterns, even though previous studies that attempted to use neuroimaging to define the disorder remain controversial.

While giving normal children these performance focusing cogniceuticals is causing a bit of an ethical stir, Judith Rapoport, chief of child psychology at NIMH, conducted a similar trial 20 years ago. The same stimulant was given to children at a higher dose. Researchers looked only at how the stimulant changed children's behavior as they performed tasks. The stimulant improved attention span in the children, regardless of whether they had ADHD. This time, I guess we'll see where specifically there might be a difference in brain activation between the groups and see if we can make a dent in this profoundly disruptive problem.

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August 03, 2004

The Future of Hearing (Neuroelectronics and Audioceuticals)

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Posted by Zack Lynch

Don't miss the next Bay Area Future Salon on August 12th, where Dr. Mike Chorost, SRI International, and my brother, Dr. Eric Lynch, Sound Pharmaceuticals, will discuss the present state of neural technologies for treating deafness and their likely future. Dr. Chorost will open by explaining how the most advanced neurostimulation technology on the market, the cochlear implant, enables the deaf to hear. Dr. Lynch will follow with a discussion of audioceutical technologies may actually prevent and cure deafness.

Where: Thursday 12th of August. SAP Labs North America, Building D, Room Southern Cross, 3410 Hillview Avenue, Palo Alto, CA 94304. 7pm.

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June 29, 2004

Eyetech Pharmaceuticals - A Sensoceutical Pioneer

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Posted by Zack Lynch

Eyetech Pharmaceuticals and Pfizer recently applied with U.S. regulators to market their experimental drug for age-related macular degeneration (AMD), the leading cause of blindness in older people.

Eyetech is one of a growing group of sensoceutical companies developing therapeutics to stem sensory decline associated with aging. Today, over 15 million people in the United States suffer from some form of AMD. This number is expected to increase significantly in the coming years as life expectancy continues to climb. In addition to sight, other sensoceutical companies are currently working on treatments for other sensory system disorders, such as: hearing loss, taste disorders, and chronic pain.

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May 11, 2004

Trouble Sleeping?

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Posted by Zack Lynch

About 70 million Americans suffer from sleep problems, according to the National Center for Sleep Disorder Research. Each year, sleep disorders, sleep deprivation, and sleepiness add an estimated $15.9 billion to the national health care bill. Additional costs to society for related health problems, lost worker productivity, and accidents have not been calculated. But help seems to be on the way.

Recently, Sepracor won FDA approval for it's new anti-insomnia drug, Estorra while Neurocrine Biosciences expects to apply for approval this year and bring Indiplon to market in the second half of next year.

While many might argue that there is a strong profit motive behind "medicalizing sleep," Carl Hunt, director of the federal government's National Center on Sleep Disorders Research, said the opposite problem is still true: "The issue is not over-diagnosing. The issue at this point in time is still under-diagnosing."

If you are having trouble sleeping you might consider testing your sleep I.Q., checking out these basic tips for a better nights sleep, or if you are an animal lover, then you might look to blame them.

Update: The U.S. market for prescription sleep products, not including off-label (not indicated for the treatment of insomnia) use of central nervous system agents for the treatment of insomnia, was approximately $1.5 billion in 2002. The U.S. prescription sleep agent market grew at a rate of almost 25 percent for the past two years, according to IMS Health information.

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April 01, 2004

Are You Wired to be Fat?

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Posted by Zack Lynch

A study published in today's Science shows that the appetite-regulating hormone leptin causes neurons to be rewired in areas of the brain that regulates feeding behavior.

The research team, led by HHMI investigator Jeffrey M. Friedman, provides an important clue about how leptin exerts its effects on the brain to cause decreased food intake and increased energy expenditure.

"Leptin decreases feeding and fat deposition by acting on two classes of neurons. Leptin suppresses the activity of neuropeptide Y (NPY) neurons and it enhances the activity of proopiomelanocortin (POMC) neurons. Conversely, the absence of leptin increases feeding and fat deposition by exciting NPY neurons and suppressing the activity of POMC neurons."

So here is the problem for the neuroceutical industry:

“If you just look at a region of the brain, you can't tell one neuron from the next,” Friedman said. “And in this case, you had in one brain region neurons theorized to stimulate appetite right next to those believed to inhibit appetite.”

As I mentioned in Addicted, Overweight? specificity at the neuron level will be necessary to develop effective neuroceuticals. Not an easy task.

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March 15, 2004

Audioceuticals Will Prevent Hearing Loss

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Posted by Zack Lynch

Sound Pharmaceuticals researchers are quickly moving forward on developing neuroceuticals to stem hearing loss. Hearing loss is the third leading chronic disorder and exceeds the number of persons with either diabetes or visual loss combined.

"According to the NIH, CDC and NIOSH, hearing loss is the most common neurosensory disorder and the most common occupational disease. Hearing loss is found in all age groups and can seriously compromise the quality of life or job performance of those affected.

Hair cell regeneration to improve or restore hearing in persons with permanent hearing loss is a significant product pipeline for Sound Pharmaceuticals, Inc. SPI previously announced that its patent, Method for the treatment of diseases or disorders of the inner ear, was issued in Europe, effective Oct. 1, 2003."

(disclaimer: Eric Lynch, VP of Research, is my brother).

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February 19, 2004

Pharma's Horizontal Future

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Posted by Zack Lynch

Drug development is hard and costly. Clearly, something must change if the scenario of $10m drugs with 2 year development times is going to emerge by 2020. (see #7).

To get an idea of the cost issues facing today's pharma industry, I highly recommend Derek Lowe's recent coverage of the subject. For example, in...

- Darn those R&D costs, he rightly agrees with others on $805 million cost/drug
- How drugs die he reviews how 46% of all failures result from lack of efficacy in Phase II
- Drug prices and costs he shares his concerns over Phase III failure rates
- More on high prices and otherwise he investigates pricing power and patents

As I explored last year in pharma's coming industrial implosion, the entire industrial organization (indeed the economic geography) of the pharmaceutical industry is in for a radical change as we enter the era post-genome pharmacology.

Helping support my distant projections is a piece by 35 year biotech veteran, G. Steven Burrill in the most recent Drug Discovery World: (not yet on-line)

"We are about to see the pharmacoeconomic model change...the integration of genomic information into drug design...will make the firms horizontally, instead of vertically integrated."

"Targeted pharmaceuticals and work for the betterment of healthcare by reducing the cost and time of development and time to market. As we better understand the body as a biologic system (systems biology)...It is not just changing the healthcare paradigm, it is changing life itself."

Getting from time A to time B will not be simple. Trillions of dollars (and even more Yen and Euros) of investment capital in NBIC-related technologies will be needed if we are to see this level of change in the coming decade. More on the shifting economic geography of the pharma industry in time...

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Astrocytes Are Stem Cells

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Posted by Zack Lynch

Howard Hughes researchers report in today's Nature that they have found a third type of stem cell in the human brain, astrocytes. Until recently, astrocytes were thought to provide only a supportive, nurturing environment for the neuron, while this research shows that they can actually function as stem cells.

As Nadar Sadia, one of the primary researchers on the project details, "The astrocytes can form new stem cells and are able to generate all three types of mature brain cells...They form a novel ribbon-like structure in the brain's lateral ventricle. Stem cells from comparable areas in the rodent brain follow a distinct path from their place of origin to the olfactory bulb (a brain region that processes smells), where they create new neurons."

“This speaks to the plasticity of the human brain,” he said. “Certain cell types may have hidden potential.” These subtypes of astrocytes appear no different from any other astrocytes, implying that “it's possible that other astrocytes in other regions of the body have the same potential.”

Randall Parker's comment on this finding hits the nail on the head. "What seems surprising about this result is that only now in the year 2004 has anyone even checked to see if astrocytes can become nerve cells." Well, the research probably began several years ago, but the point is well taken.

As I discussed in "Yes, Your Brain is Very Complex" and Tom Ray detailed in his five part Brain Waves series on "Exploring the Brain's Boundaries", our understanding of the brain's complexity continues to grow. This is just another classic example.

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January 27, 2004

Wake Up Drivers!

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Posted by Zack Lynch

As I predicted early last year, Provigil (short for promotes vigilance) was just approved for use by U.S. regulators to market its narcolepsy drug to truck drivers and others whose work shifts make it difficult to stay awake on the job.

Note: the "others" category is quite large.

Good bye coffee, hello Provigil.

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December 17, 2003

Addicted? Overweight?

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Posted by Zack Lynch

As the Economist's latest survey points out this week, "the trouble with people is that they want to be healthy, and they want their food to be tasty, cheap and convenient." The problem they assert is that these are all contradictory things.

"Once people are used to fatty, sugary and salty foods, they find it hard to give them up."

In sensoceuticals and super tasters I suggest that we are on the verge of being able to influence our evolutionarily defined neural chemistry. Our sense of taste will be one of the first targets as sensoceuticals begin to trick our pallet. Combine this with the coming end of addiction and maybe you'll be able to have that protein-infused nicotini after all.

So whether you are doing the low carb thing, or you are addicted to laughter, in 20 years you'll be able to taste and feel a lot more how you want. Or maybe we won't need these tools after all, as new figures suggest that over the past year Americans got very slightly thinner for the first time in recorded history.

Regardless of the current war on fat, advances in neurotechnology will surely change our lives and throw a wrech into projections like the U.N.'s latest population report Population 2300 as people live longer, happier lives.

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November 16, 2003

How Hard is Drug Development? HARD

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Posted by Zack Lynch

Derek Lowe explains from personal experience that innovation in drug development isn't easy:

"And it's not like there aren't plenty of highs and lows in what we're pleased to call "normal" drug discovery. It should be enough.

But it isn't, not always. These roll-the-dice ideas keep occuring to me, and some of them just seem to have to be tried out. It's hard dealing with the results, which (so far) have been relentlessly negative. That goes for this current idea, which is a little over a year old, and for the ones I've had in past years. None of the really good ones have worked, not one. And that bothers me, as it would bother anyone. But I think, eventually, it would bother me more if I never tried. Here goes, again.

From all of us who will eventually benefit from your years of hard work, I'd like to say thank you and make a toast to you as a future famous man.

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October 31, 2003

Boo: Trick that Treat

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Posted by Zack Lynch

Halloween turns millions of kids (and some adults) into candy-loving monsters with more than ample supply of candy to satisfy their "sweet tooth." Now, HHMI researchers have moved closer to understanding why some people cannot resist the impulses brought on by sweets.

The findings, reported in today's issue of the journal Cell details how the researchers created mice with the same sweet-tooth preferences as humans by inserting the gene that codes for a human sweet-taste receptor protein into the animals. They also inserted an entirely different receptor gene into the taste cells of mice, thereby producing animals that perceive a previously tasteless molecule as sweet.

This research is a wonderful step in the development of flavorceuticals, a type of sensoceutical focused on our sense of taste. Now just imagine if we can get them to figure out how to make all those yucky foods taste sweet.

Happy Halloween! Casey and I are going together as Sydney Bristow and Michael Vaughn from Alias.

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October 23, 2003

Memory and Today's Tools

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Posted by Zack Lynch

Derek Lowe recently posted a very good explanation of the presumed mode of action of the new Alzheimer’s drug memantine.

Memantine has some affinity for a wide range of receptors in the brain, but at the doses that are seen therapeutically, the relevant interactions seems to be with the NMDA receptor....The weird thing is, memantine is an antagonist; it blocks NMDA signaling. So at high doses, it actually interferes with memory....At clinical doses, the compound does play against type and seem to improve memory. The best guess for how this works is through a mechanism for neuronal injury in Alzheimer's. Too frequent (and too prolonged) firing of excitatory pathways like NMDA have long been associated with cellular damage in the brain, and this seems to be going on in AD as well...

There is some evidence that neurons with NMDA receptors are lost in AD, but it’s hard to explain the improvement in cognitive performance of some patients if you are merely stopping or slowing damage. Also memantine has been shown to have a short term effect on memory and memory related cellular plasticity. Why not consider this evidence that memantine is working through a more subtle mechanism than preventing excitotoxicity?

NMDA is believed to function in learning by giving a neuron “memory” of previous activity. Since we have to be picky about which memories are stored and which can be forgotten, NMDA is thought to be a sort of memory “bouncer” determining whether the stimulus is strong enough to be laid down permanently, or whether you really don’t need to remember where you left your keys.

So a reasonable theory would be that in Alzheimer’s, NMDA is underactive and is not letting in any new memories. But the efficacy (though slight) of memantine suggests that maybe NMDA is overactive, letting in any memory at all and promoting the cellular changes that allow memories to be stored at random. Without any barrier for memory formation, perhaps a neuron can’t distinguish between important and unimportant events, so it appears that nothing is stored, when really “everything” is stored and each event instantly erases the last event. Memantine can reduce the activity of NMDA and restore its selectivity for the right memories.

Complicated explanations may not suit a pharmaceutical company, but understanding the true therapeutic nature of current pharmaceuticals will be an important part of future neuroceutical development. For example, SSRI's like Prozac take several weeks to be effective, but for years pharma claimed that the anitdepressant effect was due to a short term reduction in serotonin reuptake. The fact is we still don't know why SSRI's have the effect they do.

Thanks Casey.

Comments (3) | Category: Cogniceuticals | Neuropharma

October 15, 2003

Neuroceuticals are Tools

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Posted by Zack Lynch

Neuroceuticals are tools. They hold the promise and peril of any new set of tools.

Tools like the oxen plow, railroads, electricity, automobiles, planes, cell phones, and the web, have all in one way or another been used for good and evil purposes.

By providing new tools for people to manage their behavior and empathize with others, neurotechnology represents potential breakthroughs in human productivity, political stability and ecological balance. In the wrong hands, this technology also could be used for mind control, coercive truth detection or as neuroweapons that have the potential to erase the memories or feelings of entire populations.

Neuroceuticals, although perhaps daunting and perhaps a bit scary because they have the capacity to influence our moods and perceptions, are being developed rapidly. My purpose is to help begin a broad and thoughtful public discussion of the social implications of neuroceuticals before they arrive. My intention is not to promote them but to highlight the fact that they will emerge no matter what stringent standards may be adopted by most of the world's governments.

My thinking is that neuroceutical adoption for competitive advantage will likely begin outside the jurisdiction of western governments, as the regulatory process will be slow to adapt. It is in the smaller countries or regions that initial adoption will occur where the political process can be persuaded quickly.

Moreover, when people within large multinational companies begin to experience the advantages these new tools bring, the pressure to accept and legalize them will grow quickly. Governments and regions that don’t won’t be able to compete. It would be as if a region didn’t allow telephone service.

Neuroceuticals will one day be considered very ordinary and disappear into people’s daily lives like all successful technologies do. Just like irrigation is an invention we don't think about much anymore, neurotechnology will in time seamlessly become part of our lives.

Comments (1) | Category: Neuropharma

October 08, 2003

Accelerating Innovation with Neuroceuticals

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Posted by Zack Lynch

As I alluded to in Forecasting Happiness, neuroceuticals will play a prominent role in accelerating productivity across all economic sectors during the neurotechnology wave.  One pervasive process that will be affected is the social process of innovation.  Innovation is a key determinant of organizational success wherein cognitive assessment and emotional compassion combine to accelerate the creation of new knowledge. 

Over the past several decades access to a growing global information web has improved innovation cycle times across every industry.  Over the next decade this trend will continue as social networks (opinions, thoughts and concerns) become embedded across this information sea, creating a knowledge web that is vastly more reliable. 

By improving cognitive clarity and emotional stability , neuroceuticals will make possible new behavioral repertoires that most of us cannot consistently attain today.  For example, enhancing an individual's working memory with cogniceuticals will play a role in extending individual creativity, a critical component of the innovation process.

As different aspects of mental health are better understood, more parts of the innovative process will be impacted such as accelerating learning via cogniceuticals to enhancing interpersonal communication with emoticeuticals. As neuroceutical usage spreads across industries it will create a new economic “playing field” wherein individuals who use neuroceuticals will achieve a higher level of productivity than those who don’t. 

The resulting competitive gap will be substantial. To put this in historical perspective, imagine the competitive advantage that a team living in the year 2003 with the Internet as their information source has over a group living in 1953 that must rely on the local library.

Comments (0) | Category: Neuropharma

September 29, 2003

A Chemistry of Mind

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Posted by Tom

by Tom Ray

The goal of mapping "receptor space" is to chart the relationships between complex alterations in chemical signaling, and resulting changes in mental states. These data are expected to provide an empirical basis for the development of an understanding of the chemistry of mind. To do this we need to understand what mental states are associated with various regions of the receptor space. We need to understand what kinds of interactions between transmitter systems and neural pathways result from chemical perturbations into various regions of receptors space.

This knowledge can help us to build a theoretical foundation for the rational design of drugs for the treatment of mental illness. In a loose sense, mental illnesses are also a kind of perturbation in receptor space. We need to determine what regions of receptor space are associated with these illnesses, and develop a pharmacology for these regions.

We do not yet understand why different individual members of this family (e.g., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are more effective in treating different individual patients. It is plausible that these differences in efficacy derive from the interactions of the different receptor binding profiles of the different antipsychotic drugs, with the specific characteristics of the disorders manifested by individual patients.

If we can develop a detailed knowledge of the relationship between chemical balance and mental state, methods for treating mental illness can be greatly improved. The atypical antipsychotics are some of the most effective drugs in treating the most difficult cases of schizophrenia. These drugs bind to a very large number of receptors, and therefore cause complex perturbations in "receptor space".

The understanding of the chemistry of consciousness is the ultimate goal of my research. By mapping receptor space we will be able to create a more rational basis for developing effective treatments of mental disorders. Please feel free to email me directly if you are interested in learning more about my research.

Comments (0) | Category: Neuropharma

September 26, 2003

A Dynamic Neurochemical System

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Posted by Tom

by Tom Ray

Let's consider a brain-centered reference frame, in which the origin is based on some arbitrary absolute levels of activity at each receptor population. The origin could be the time-averaged activity at each receptor, or no activity at each receptor, it doesn't matter much. In this reference frame, the state of the brain is constantly on the move, regardless of medication. We can think of it as a complex dynamical system, in which the trajectory likely does not traverse the entire receptor space, but rather follows certain high-dimensional orbits, and switches among many "attractors", where the attractors represent the major emotional states and moods, and whatever other mental phenomena the chemical systems are mediating. Mental illnesses can be thought of as pathological attractors.

In this more dynamic reference frame, the notion of drugs perturbing the brain along a vector of binding affinities in receptor space seems simplistic. It is more likely that drugs will create a perturbation along the binding vector, thereby pushing the system into a new attractor.

As pharmacologists, we want to understand how patterns of activity at receptor populations associate with mental phenomena. We want to get to know the pharmacology of the attractors. It seems unlikely that the attractors will be on-axis, resulting from changes in the activity of single receptor populations.

We have our hands on the receptors and we are enchanted by them. We have come to think of selectivity in terms of receptors, and in the process we have lost sight of the mind that we wish to understand. There are other approaches to thinking about pharmacological selectivity. Selectivity can be defined in terms of different or distinct behavioral or subjective mental effects produced by drugs.

The conventional approach to pharmacology is to find a drug that is receptor selective, and then observe its behavioral effect. An alternative approach is to find a drug that produces a distinctive behavior, and then observe its receptor binding profile. I believe that it is this alternative approach that holds the greatest promise for understanding the pharmacology of the attractors, and thus the major mental states mediated by receptors. The two approaches are complementary, and we need both to provide the most comprehensive understanding. The new approach is only now becoming possible, as it requires the full post-genome pharmacology provided by PDSP.

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September 25, 2003

Mapping Receptor Space

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Posted by Tom

by Tom Ray

I would like to share a metaphor, or image, that I use when thinking about the new pharmacology: receptor space.

Imagine a coordinate system based on receptors, one axis for each receptor ("receptor space"). This notion of "receptor space" is in the reference frame of the unmedicated brain. Drugs perturb the system from its pharmacological origin by altering the activity of transmitter and receptor systems, through increasing or decreasing transmission or transmitter levels, or up or down regulating receptor populations.

From a pharmacological point of view, the origin of the receptor space represents the state of an individual brain at any moment, without the application of any drug. When a drug is applied that binds to receptors, it shifts the balance of activity of the brain away from the origin, by a vector representing displacement along the axes corresponding to the receptors where the drug binds (and perhaps others due to secondary interactions).

The distance of the shift represents the affinity of the drug for the receptor, or the degree to which the drug activates the receptor. Negative axes could correspond to blocking or deactivation of the receptor. For convenience, I would like to refer to molecules with a non-zero value on only one axis as "on-axis", and molecules with a non-zero value on more than one axis as "off-axis".

These kinds of changes occur spontaneously and constantly in the unmedicated brain. Thus our pharmacological reference frame, of the unmedicated brain at the origin, is a very dynamic one.

Comments (0) | Category: Neuropharma

September 24, 2003

Post-Genome Pharmacology

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Posted by Tom

by Tom Ray

The completion of the human genome has revealed the tremendous complexity of the chemical signaling pathways in our bodies. There appear to be over three hundred different kinds of receptors expressed in the brain.

To understand how variations in the activities of these chemical signaling pathways can combine to produce mental states and mental disorders, we need to develop an empirical understanding of the influence of these systems on mental states. This understanding must include interactions between different chemical signaling systems, as well as the role of individual systems. The cloning and development of receptor binding and functional assays for a large number of receptors is opening a new "post-genome" era of pharmacology, which permits us to look at the global effects of drugs on the brain and body.

The National Institute of Mental Health set up a Psychoactive Drug Screening Program (PDSP) using this new post-genome approach. PDSP is the "supercomputer" of pharmacology. It is a facility, still under development, that allows us to screen drugs against the entire human "receptome" (all receptors in the human body).

It is a facility like a supercomputer, that is so massive and expensive, that in this case, only one can exist. Therefore NIMH has set up one such facility, and makes its screening services available to researchers, like the supercomputers at the National Center for Supercomputing Applications (NCSA).

A few years ago, it was a very difficult task to screen a drug against a single receptor, to deterine if the drug binds to the receptor, and if so, what it does there (blocks, activates or de-activates). In the past, pharmacologists were like the blind men and the elephant only able to look at one or a few parts of the chemical system. Now for the first time it is becoming possible to look at the whole system.

Comments (0) | Category: Neuropharma

September 23, 2003

The Pharmacological Approach to Brain Mapping

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Posted by Tom

by Tom Ray

  1. Why are there so many different neurotransmitter receptors in the brain?
  2. What is the functional role of each, and how are they organized in the brain?
  3. How are the activities of these transmitter systems and their interactions associated with mental states?

In short, what is the chemical architecture of the brain and the mind that emerges from it? The answers to these questions should ultimately provide a firmer basis for understanding mental illness and developing treatments.

The pharmacological approach to these questions is to develop compounds that bind selectively at receptors, and activate or block them, and use them as probes to receptor function. When the molecular mechanisms of action of a drug are known, they can be correlated with the behavioral effects in animals or the subjective reports of humans, to understand the mental correlates of their underlying biological effects. When used in this way, pharmacology is a means of exploring the chemical organization of the brain and mind.

Peter Kramer's book "Listening to Prozac" introduced the pharmacological approach to the general public. The title "Listening to Prozac" means that we learned something new about the nature of the human mind by observing the effects of prozac.

Prozac was developed to treat depression, but when it was prescribed to large numbers of people, it was discovered that it also changed personality (from timid to self-confident). Before this unplanned experiment, it was not known that such aspects of personality were under chemical influence. By listening to prozac, we learned something about the chemical organization of the human mind.

Although pharmacology is generally thought of as a branch of medicine that uses chemicals to treat illness, pharmacology can also be used as a method of probing living systems to understand how they are organized and how they function.

Comments (2) | Category: Neuropharma

September 22, 2003

The Chemical Architecture of the Mind

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Posted by Tom

by Tom Ray

Understanding the chemistry of the brain and the mind that emerges from it is one of the remaining great frontiers of science. Developing a fundamental understanding of the chemistry of the mind will provide us with a deeper understanding of ourselves and a theoretical basis for a more rational system for treating mental disorders. Without an *understanding* of the chemistry of the mind, pharmacology remains a trial-and-error "science".

The brain is a chemical organ and our mental states are dramatically altered by chemical shifts. Chemical shifts can be caused by drugs but they also occur naturally. Moods and emotions are likely to have chemical foundations, and even without the influences of drugs, much of our mental life is a chemical dance. Features of the human personality, such as the spectrum between timidity and social confidence, can be influenced by chemistry. A wide variety of serious mental disorders, from depression to schizophrenia, have yielded to effective chemical treatments, suggesting that chemical imbalances may underlie some of these disorders.

Different disorders (see DSM-IV, 2000) yield to different chemical treatments, indicating that each disorder is associated with a specific chemical imbalance. Yet there is currently no rational way to predict which antidepressant is more likely to work than another in a depressed patient or which antipsychotic will work in a specific schizophrenic patient. Furthermore, no single abnormality in any neurotransmitter or in any of its enzymes or receptors has been shown to cause any common psychiatric disorder. It is currently believed that the major mental disorders are the result of an accumulation of factors that together cause the disorder.

Comments (8) | Category: Neuropharma

September 19, 2003

Exploring the Brain's Boundaries (A Six Part Blog by Tom Ray)

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Posted by Zack Lynch

Next week Tom Ray, tropical ecologist, artificial life expert, and now neuro-mapping pioneer will share his thoughts on accelerating our understanding of the neurochemistry of consciousness by mapping what he calls "receptor space."

Tom is a true complexity expert -- an evolutionary ecologist of both the biological and digital worlds.  Tom's rich research agenda and advice have inspired me over the past 15 years.  His ecological research and conservation efforts in Costa Rica stimulated my work on disturbance behaviors in Atta cephalotes (leaf cutter ants) at Finca La Selva.  His work at the Santa Fe Institute on Tierra, a distributed digital artificial life reserve, pushed the science of complexity to new levels.

Hundreds of articles have been written about Tom's previous research.  I'm confident his approach to mapping the potential mental states that the human mind can experience will prove to be his most important work to date.  Few people have first-hand experience with multiple complex evolutionary systems.  It is this deep perspective that should allow him to contribute significantly to our understanding of the human mind.

Tom Ray is currently a Professor of Zoology at the University of Oklahoma and an Invited Researcher at ATR Human Information Sciences Laboratories, Kyoto, Japan.

As Paul Allen mentioned earlier this week, understanding the brain and how the mind emerges from it remains one of great frontiers of science.  I'm honored to have Tom Ray, for the first time, share his new research direction with us on Brain Waves.  Expect great thoughts!

Comments (0) | Category: Neuropharma

July 07, 2003

Sensoceutical Development

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Posted by Zack Lynch

Randall Parker blogs on an interesting development in our understanding of how pharmacological agents can inhibit and enhance human sensory system performance.  Citing the researchers:

"We are at the beginning of an era where we can interact with the brain. We can apply what we know about brain plasticity to train it to alter behavior. People are always trying to find ways to improve learning. What we tested is unconscious skill learning. How far could this carry to cognitive learning?…that remains to be seen," said Dinse.

Published in Science, the research showed that stimulation combined with methamphetamines could improve tactile sensitivity of people's fingertips.  It is research like this that focuses on the basic neuroscience of sensory system learning that will lead to sensoceutical breakthroughs in the coming years.

Comments (0) | Category: Neuropharma

June 25, 2003

Exceptional Thoughts

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Posted by Zack Lynch

Daily, weekly, monthly and annually great thoughts of produced.  Here are a few of the recent best:

Daily: Richard Gayle's Living Code blog

Weekly: Science Magazine

Monthly: Seed Magazine (June/July print version)

  • The Strange Case of Dr. Sell, Drugging the Accused: Important Supreme Court decision
  • The Neuroscience of Proust: Brilliant artists are many times ahead of science

Annual (books):

  • Law and the Mind -- Biological Origins of Human Behavior by Margaret Gruter:  Margaret's insight into how evolutionary biology can inform our legal system is still as relevant today as it was when it was first published 20 years ago.
  • MWO-It was an honor to be the fourth reviewer of a manuscript written by someone most of us know.  Unfortunately, I'm unable to share the enticing personal perspective of neurotechnology developed least not yet...867-5309.

Comments (0) | Category: Neuropharma

June 05, 2003

Neurons Love to "Kiss and Run"

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Posted by Zack Lynch

The transfer of information between nerve cells occurs when chemicals called neurotransmitters are released into the synapse, the junction between neurons. Electrical impulses in the neuron cause tiny vesicles (graphic) loaded with neurotransmitters to be released into the synapse.

Today's Nature reports on a new technique that researchers have created to image the movement of individual vesicles after they have released their neurotransmitter cargo. The new technique helps answer questions like the rate at which synaptic vesicles are recycled which helps illuminate how much information nerve cells can transmit.

There are three distinct ways that a "used vesicle" can be recycled from the surface of the nerve cell once it has released its cargo:

  • "Kiss-and-Run" mode is the fastest, less than a second
  • Compensatory” mode is slower, up to 21 seconds
  • Stranded” mode leaves the vesicle stuck at the surface until the next nerve impulse triggers its retrieval

"The optical recording technique devised by Stevens and Gandhi involves genetically modifying a gene for one type of vesicle protein to incorporate a special form of green fluorescent protein. This modified fluorescent protein, developed by other researchers, does not fluoresce under acidic conditions normally present in vesicles fully loaded with neurotransmitter. However, when the vesicle releases its payload, the interior becomes less acidic and the vesicle glows a bright green."

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May 15, 2003

The Boundaries of Experience

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Posted by Zack Lynch

Synesthesia, which means "joined sensation,” is a condition wherein information obtained through one sense creates sensations in another sense. For example, when a synesthete hears a bell they would also see colors.  Many brilliant people have had synesthesia, including:

  • Physicist Richard Feynman who saw colors in his physics equations
  • Abstract painter David Hockney who visualized the colors for his paintings when hearing music
  • Composer Franz Liszt who pictured colors upon hearing musical notes.

The phenomenon is involuntary, consistent over a lifetime, hereditary, and fairly common. In fact, some form of synesthesia affects 1 in 200 people.  In its own particular way, synesthesia points to yet another way that the wiring of the brain can create different ways to experience life

Yesterday I uncovered a recent 17 minute film made last year by Carrie Shultz that tracks the experiences of three women living with synesthesia.  She is sending me a copy.  I'll let you know how it is. 

Comments (0) | Category: Neuropharma

May 12, 2003

Neuroceuticals Categorized

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Posted by Zack Lynch

As the brain imaging bottleneck is overcome allowing live neuron-specific resolution of our brains, this information will be combined with data from the ‘whole biochip', making possible a new sets of tools that I am calling, neuroceuticals.  

Neuroceuticals act to reduce the severity of a mental disorder or enhance an aspect of mental health.  They can be broadly categorized into three classes:

Obviously this categorization is simplified, as our senses, cognition and emotions are inextricably interconnected.  However, by introducing these terms, it should make discussions of their interdependency clearer over time.

How will complex mixtures of neuroceuticals that simultaneously influence multiple aspects of human behavior impact social relations? How will a person who is slightly less depressed, slightly less anxious, slightly more aware, and with slightly better recall behave? 

By influencing multiple characteristics along varying gradients, behaviors will emerge that will culminate into a substantially different behavior repertoire than people currently encounter.  In effect, a different “playing field” will arise wherein people will act perceptually different than if one were to just enable people to be happier.

It is important to view neuroceuticals not as drugs that unnaturally change the human condition.  Rather neuroceuticals are tools that humanity is developing to help each of us better control our mental health, allowing us to organize more effectively in an ever-complex world. 

The breakthrough required to develop true neuroceuticals are still 10-15 years off.  However, as they emerge individuals and organizations will adopt these new tools just as information technology, motorized transportations systems, electricity, steam engines, and canals have been leverage to increase humanity's overall control and effectiveness of physical and information assets.

Comments (2) | Category: Neuropharma

April 25, 2003

Pharma's Industrial Implosion

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Posted by Zack Lynch

An important conversation between Richard, a biotech pro, and Derek a pharma veteran, highlights the pathetic state of the current drug discovery and development process. 

Both point out how Pharma's current top down development process is tedious, disconnected and in many cases just don't work.  Although Richard's prescription seems logical on paper, the reality of industrial reorganization coming from the inside is a long shot.

Industries evolve in a similar manner as ecological systems, via punctuated equilibrium. Industries progress slowly and then suddenly a new organism/organization that has been evolving along the fringe emerges to replace the parent species by taking advantage of a new adaptation/technology.

The history of economic geography is full of examples of how industries evolve between being vertically integrated structures to vertical disintegrated ecosystems, driven primarily by the disruptive effects of a new organizational species.

The current pharmaceutical industry is highly vertically integrated.  Although attempts are being made to extend their expertise through alliances and acquisition, the history of life proves time and time that most powerful driver of change is the emergence of an organization that leverages a specific adaptation to out fight, out wit and out compete the current dominant species.

With gene chips just beginning to fulfill their promise, I believe that the organizational form that will dominate the future of drug development will be the one who cracks the proteomics bottleneck and leverages this new information to dominate its ecology.  On that note, I'd give the upper hand to a biotech company that is most likely not even on today's industrial landscape.

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April 18, 2003

The End of Drug Addiction

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Posted by Zack Lynch

Research into the neurobiology of drug addiction is progressing rapidly, leading prominent researchers to claim that within the decade there will be effective treatments for drug addiction

But will these new treatments actually stop people from seeking pleasure inducing drugs? Only time will tell.

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April 06, 2003

In the Pipeline: A Drug Development Blog

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Posted by Zack Lynch

A warm welcome to Derek Lowe who has joined Corante's blogging team to share his knowlege and insight into the complex world of drug development.  

In The Pipeline: Drug Discovery will cover: "recent developments in drug discovery and medicine and the IP issues and financial implications they have, along with general thoughts about research. Also likely to make an appearance: occasional digressions into useful topics like which lab reagents smell the worst." I highly recommend taking a look at the three months of blogs already in his archives.

The future of neurotechnology and the drug development process are intimately related as my blogs on emotions, sensoceuticals and barriers to drug delivery have previously pointed out.  Derek's daily focus on the drug development process along with Richard Gayle's "Living Code" blog on biotechnology will be excellent sources of inspiration and information as I try to untangle our emerging posthuman society.

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March 31, 2003

Sensoceuticals and Super Tasters

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Posted by Zack Lynch

Substantial variation in taste sensitivity exists in humans. Understanding taste's relationship to diet and other behaviors like smoking will have important implications for human health.

Taste plays a crucial role in food choice, allowing people to identify beneficial foods those with high caloric value (typically sweet) from foods likely to be toxic (usually bitter).  Breakthroughs in taste research began in 1931 when Science published the finding that many individuals are unable to taste the compound, phenylthiocarbamide (PTC), a relatively bitter compound. It turns out that one-fourth Americans cannot taste PTC.

Companies like IFF (International Flavor and Fragrances) have been focused on developing "better" tasting food for years while start-ups like Senomyx are working on products that block bitter tastes in coffee, make low-sodium snacks taste salty, and block unpleasant odors. 

Although these don't come close to the new experiences that are on the horizon, but continued research by sensory scientists should lead to the development of new taste specific sensoceuticals in the coming years.  At the very least this might mean better tasting MREs.

Comments (1) | Category: Neuropharma

March 24, 2003

Barriers to Drug Delivery

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Posted by Zack Lynch

This month's Scientific American describes many of problems faced in getting pharmaceuticals to their intended targets throughout our bodies. Delivering neuropsychopharmaceuticals to our brain remains even more of a problem.

Drug delivery to our brain can occur through several methods: orally (pills), gaseous/inhaled, intramuscularly (skin patch), intravenously, and neural injection.  The method used greatly influences the amount of the drug that is required for the same effect to be observed.  For example, a single dose of an amphetamine creates the same effect but requires hugely different volumes depending on the method of delivery:

  • 1000 micrograms if ingested orally
  • 100 micrograms if injected or inhaled
  • 10 micrograms if injected in the cerebral spinal fluid
  • 1 microgram if injected onto the neuron

The primary delivery limiters are the digestive system and the blood brain barrier.  Many effective treatments for mental illnesses have been kept off the market due to the inability to safely deliver therapeutic chemicals whose large molecular sizes makes it impossible for them to pass the blood brain barrier. 

Neural chips may play a role in effectively delivery, but the cultural "acceptability barrier" of implanting chips into our brains will likely remain the largest obstacle to adoption on wide scale for some time to come.  It is one thing if you are deaf and get a cochlear implant, it is another to be willing to go through a surgical procedure if you are a bit anxious or occasionally depressed.  The likely pathway will depend on the pay-off for the patient.  One thing is for sure, more effective drug delivery systems will require new partnerships and new techniques to make precise delivery possible.

Comments (2) | Category: Neuropharma

March 20, 2003

Sensoceuticals to Restore Hearing Loss

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Posted by Zack Lynch

To date, media attention across the emerging field of neurotechnology has primarily focused on neural prosthetics that are electro-mechanical in nature.

For example, to help the hearing impaired, cochlear implants have been developed that translate sound waves collected via a tiny microphone into electrical impulses. Most people with profound deafness have lost the ability to translate the acoustic energy of sound into the electrical signals carried to the brain by the 30,000 fibers of the auditory nerve.  Cochlear implants bypass the external and middle ears by using electrical stimulation of electrodes implanted in the cochlea to reintroduce the signals carried by auditory nerve fibers to the brain.

As exciting and important as electro-mechanical advances like this are, they represent just one type of neurotechnology that will be developed in the coming years to restore and enhance human sensory systems, such as hearing. 

Sensoceuticals, sensory-specific biopharmaceuticals, use a different approach to restore and enhance human sensory systems.  Sensoceuticals leverage the natural regenerative capacity of our genes, proteins, and neurons to re-grow damaged sensory tissues and extend sensation capacity.

For example, sensoceuticals for hearing will be able to prevent and restore hearing loss. Current research indicates that the inner ear can be protected from the irreversible effects of noise damage using sensoceuticals. This will be an important breakthrough for soldiers who, due to the complexity of the today’s battlefield, can’t wear earplugs to protect their ears.

For those people who already have substantial hearing loss, researchers are also optimizing compounds that antagonize specific cell cycle proteins resulting in new cell division or proliferation. Most exciting is that these newly dividing cells have the capacity to become replacement auditory hair cells, restoring hearing loss for the deaf or partially deaf.

As the field of neurotechnology evolves it will be interesting to see how the developments occurring “from the inside” begin to mingle and compete for funding resources with advances coming “from the outside.”

Comments (3) | Category: Neuropharma