Viagra's Enzyme Action May Give Pfizer Schizophrenia Advance

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Patients discontinue the medication because they say it makes them lethargic and withdrawn and can cause weight gain that is annoying and dangerous, as it can lead to diabetes, says Robert Freedman, chairman of the department of psychiatry at the University of Colorado at Denver. Current drugs also don't help patients overcome difficulties in making judgments, which can hinder relationships and employment, Freedman says.

1950s-Era Remedies

There has been little innovation in the way schizophrenia treatments work since the 1950s when the first drugs came on the market that allowed victims to live outside mental hospitals, says Jeffrey Lieberman, chairman of psychiatry at Columbia University College of Physicians and Surgeons in New York and director of the New York State Psychiatric Institute.

The older drugs, and the newer ones like Zyprexa and Risperdal, reduce the activity of dopamine, a chemical in the brain that regulates movement, feelings of pleasure and emotions. Scientists say they believe excessive amounts of dopamine, or brain cells' heightened sensitivity to the chemical, trigger troubling thoughts and feelings.

``With schizophrenia, we just by happenstance stumbled on a treatment 50 years ago that we've just been cloning since and haven't made much further progress,'' says Lieberman, who has worked with Pfizer on unrelated research projects. He says one challenge in treating schizophrenia is that no one knows exactly why some people develop the dopamine-related responses.

Rodent Experiments

Preliminary studies suggest Pfizer's new treatment may provide an advance, the company's scientists say. They point to experiments in lab rodents bred to have traits that mimic antisocial human behavior. These findings show the drug may help patients feel more engaged in their surroundings than do the current treatments. Pfizer's approach, which blocks an enzyme called PDE-10, appears to improve how the animals respond to their environment.

Pfizer won't comment on when it expects to begin human testing.

PDE-10 appears to regulate the two other molecules that control the transmission of electrical signals within cells. Scientists found that by turning off the PDE-10 enzyme they can mute the animals' reactions to a variety of stimulation.

`Very Innovative'

This fits into some scientists' hypothesis that schizophrenia is caused when the brain is unable to filter out background noises, like the humming of the lights or drone of an air conditioner. This flood of stimuli causes the brain to create a story around those noises, leading to hallucinations and paranoia, Pfizer's Jefson says. Drugs that can soften the brain's response to visual and auditory stimulation will probably reduce disease symptoms, he says.

``This is a very innovative and potentially important development strategy because it is not focusing on dopamine,'' Lieberman says. ``It is high-risk and there is no idea if it will work.''

Pfizer is in a race with other drugmakers, including London- based AstraZeneca Plc and Eli Lilly, to produce drugs that sharpen patient awareness and other cognitive skills, says Kate Hohenberg, a health-care analyst at Decision Resources Inc., a market research firm in Waltham, Massachusetts.

Amgen Inc., a biotechnology company based in Thousand Oaks, California, and Memory Pharmaceuticals Corp. are also exploring ways to use the PDE-10 enzyme to treat certain psychological disorders, according to a statement last October by Memory Pharmaceuticals, a Montvale, New Jersey-based company focused on treating psychological conditions.

No FDA Guidelines

Pfizer and its competitors say it may be difficult to prove that drugs like this one are advances over existing pills. That's because the Food and Drug Administration doesn't have guidelines to measure whether a medicine improves a person's judgment, mental awareness or social interactions.

While Pfizer may be able to get a new drug approved that only eliminates hallucinations and other symptoms, company researchers say they want to be able to market a medicine that does more.

``It is very frustrating to have this great unmet need, and the regulatory path is not clear, and there is not much pharma can do about it,'' Hohenberg says.

Mental Judgment

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Thomas Laughren, the FDA's head of psychiatric products, says the agency has talked with ``many companies'' developing drugs to determine what data would be required to get approval for a medicine that improves a patient's mental judgment as well as quieting the disease's disturbing symptoms.

``In the beginning, you've got about a one in a hundred chance of making a compound into a medicine,'' Menniti says. ``At this stage in the game, it is probably down to about one in 10. That says nothing about this program. It says something about the process in general.''

Source: Bloomberg

Last updated: 09/06

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