New Schizophrenia Drug Shows Promise in Trials (Glutamate receptors -- Lilly)

[Guest guest]

" By the 1980s, scientists had discovered that PCP blocked brain receptors that

are triggered by an amino acid called glutamate. This led some companies and

scientists to study ways to stimulate glutamate receptors as a treatment for

schizophrenia. But the brain has many different kinds of glutamate receptors,

and figuring out how to stimulate or block them in medically beneficial ways has

proved complicated. Instead of focusing on the receptors blocked by PCP, Dr.

Schoepp concentrated on modulating the action of glutamate receptors in the

brain's prefrontal cortex, an area responsible for personality and learning. "

New Schizophrenia Drug Shows Promise in Trials

by ALEX BERENSON

Published: September 3, 2007

In a clinical trial of about 200 patients, an experimental drug from Eli Lilly

reduced schizophrenia symptoms without the serious side effects of current

treatments, according to a paper published yesterday in the journal Nature.

The drug must still be evaluated on many more patients to test for the

possibility of side effects that have not yet emerged, and it is at least three

to four years from completing regulatory review.

But schizophrenia researchers said the trial's results were surprising and

impressive, especially since the drug works in a different way from existing

antipsychotic medicines, all of which have serious side effects, including

substantial weight gain and tremors.

Lilly will begin a larger clinical trial for the drug this month. If that trial

confirms the results seen so far, the new drug could mark a breakthrough in the

treatment of schizophrenia - and open the way to a broad new class of treatments

for the disease. Schizophrenia, a devastating mental illness that affects 1

percent of adults, or about 2.5 million in the United States, usually begins in

the late teens or 20s and is marked by psychotic delusions as well as social

withdrawal and cognitive impairment.

" This is potentially one giant step forward for patients, " said Dr.

Lieberman, chairman of the psychiatry department at Columbia and the lead

investigator on a federally sponsored clinical trial of schizophrenia medicines.

" This drug may turn out to be not just a comparably good antipsychotic agent,

but a better antipsychotic agent. "

Dr. Lieberman has not been involved with the development of the medicine and

does not receive any payments or consulting fees from Lilly.

The new drug also has the potential to be a blockbuster for Lilly. Medicines for

schizophrenia and bipolar disorder are the fourth-best selling class of

medicines in the United States, with sales of $12 billion in the United States

and $18 billion worldwide last year.

The troubled history of Zyprexa, another antipsychotic medicine from Lilly, will

lead regulators and psychiatrists to scrutinize the new medicine closely for

hidden dangers, Dr. Lieberman said. When it introduced Zyprexa in 1996, Lilly

hailed it as a breakthrough with fewer side effects than older drugs. But

Zyprexa causes severe weight gain, and the American Diabetes Association has

linked it to diabetes. Internal Lilly documents show that the company played

down Zyprexa's side effects, worrying they would hurt sales.

Despite that history, psychiatrists will be eager to see whether the new Lilly

medicine works, since the existing drugs are of limited help for many patients.

Existing schizophrenia medicines, whether older drugs such as Thorazine or newer

medicines like Zyprexa, all work by blocking the brain's dopamine receptors.

But the new Lilly drug does not directly affect dopamine. Instead, it modulates

brain activity through a different set of receptors. As a result, it has the

potential to be the first truly novel treatment for schizophrenia since

Thorazine was introduced 1954, Dr. Lieberman and other researchers said.

Lilly's new drug - which does not have a name yet and is referred to as

LY2140023 - emerged from almost two decades of research by Dr. Darryle D.

Schoepp, a toxicologist and pharmacologist who joined Lilly in 1988.

For decades, psychiatrists have known that users of PCP, a street drug sometimes

called angel dust, have symptoms nearly identical to those of people with

schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain

receptors that are triggered by an amino acid called glutamate. This led some

companies and scientists to study ways to stimulate glutamate receptors as a

treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out

how to stimulate or block them in medically beneficial ways has proved

complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp

concentrated on modulating the action of glutamate receptors in the brain's

prefrontal cortex, an area responsible for personality and learning.

" This is a system that is so fundamental to the function of your brain that it

is quite powerful, " said Dr. Schoepp.

But because drugs that blocked dopamine had been the only successful

schizophrenia treatments, many researchers viewed the glutamate pathway as

unlikely to produce useful medicines, said Dr. P. Conn, director of the

Vanderbilt University drug discovery program and an expert on glutamate

research.

Dr. Schoepp deserved praise for persuading Lilly to invest in a field that

appeared to be a long shot, Dr. Conn said, adding, " He locked in very early. "

As a result, Lilly appears to have a multiyear lead over its competitors in

glutamate drugs, Dr. Conn said. Dr. Schoepp left Lilly in March to become the

head of neuroscience research for Merck. Dr. Schoepp and Dr. , the

president of Lilly Research Laboratories, both said that his departure would not

hurt the development of Lilly's new medicine

Dr. ph T. Coyle, a professor of psychiatry and neuroscience at Harvard

Medical School, said the Lilly trial validated the theory that modulating

glutamate receptors might control the symptoms of schizophrenia. Even if this

drug fails in later trials, companies and scientists are likely to pursue

glutamate research more aggressively, he said.

" When you see a company that comes up with something that's completely

different, completely out of the box, that attracts attention, " Dr. Coyle said.

Existing drugs are reasonably good at treating the hallucinations and delusions

of schizophrenia. But they are far less effective at treating the so-called

negative symptoms of the disease - the lack of motivation and emotion that leave

many patients unable to work or have normal social relationships. The side

effects of existing medicines, which affect nearly all patients, are also

severe. Older drugs like Thorazine often cause tics and movement disorders,

while newer medicines typically have fewer effects on movement but can cause

weight gain and other metabolic changes.

In the clinical trial whose results were reported yesterday, LY2140023 had none

of those side effects and appeared to work about as well as Zyprexa at reducing

symptoms. In the trial, which was conducted in Russia from August 2005 to June

2006, patients were given the experimental drug, Zyprexa or a placebo. About 100

patients received the experimental medicine.

For the drug to be approved, Lilly will need to replicate the results in larger

trials. This month, Lilly will begin a trial with 870 patients to determine the

most effective dose of the drug. That trial is expected to be complete in

January 2009, and if it is successful Lilly will probably start a large Phase

III trial that could cover at least 2,000 patients.

" We have to confirm safety and efficacy with multiple studies, " Dr. of

Lilly said. He said he did not want to offer a prediction of when Lilly might

ask the Food and Drug Administration for approval. But he said Lilly intended to

develop the drug aggressively.

" We are very actively working on this target and related targets because we

believe that this mechanism is now validated, " he said.

###

[Guest guest]

Brings to mind the fad that is starting for I think it is Namenda, an

Alzheimer's drug that is

a glutamate blocker, which some DAN! doctors are trying in autistic children.

Andy

>

> " By the 1980s, scientists had discovered that PCP blocked brain receptors that

are

triggered by an amino acid called glutamate. This led some companies and

scientists to

study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the

brain has many different kinds of glutamate receptors, and figuring out how to

stimulate

or block them in medically beneficial ways has proved complicated. Instead of

focusing on

the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action

of

glutamate receptors in the brain's prefrontal cortex, an area responsible for

personality

and learning. "

> New Schizophrenia Drug Shows Promise in Trials

>

> by ALEX BERENSON

> Published: September 3, 2007

> In a clinical trial of about 200 patients, an experimental drug from Eli Lilly

reduced

schizophrenia symptoms without the serious side effects of current treatments,

according

to a paper published yesterday in the journal Nature.

>

> The drug must still be evaluated on many more patients to test for the

possibility of side

effects that have not yet emerged, and it is at least three to four years from

completing

regulatory review.

>

> But schizophrenia researchers said the trial's results were surprising and

impressive,

especially since the drug works in a different way from existing antipsychotic

medicines,

all of which have serious side effects, including substantial weight gain and

tremors.

>

> Lilly will begin a larger clinical trial for the drug this month. If that

trial confirms the

results seen so far, the new drug could mark a breakthrough in the treatment of

schizophrenia - and open the way to a broad new class of treatments for the

disease.

Schizophrenia, a devastating mental illness that affects 1 percent of adults, or

about 2.5

million in the United States, usually begins in the late teens or 20s and is

marked by

psychotic delusions as well as social withdrawal and cognitive impairment.

>

> " This is potentially one giant step forward for patients, " said Dr.

Lieberman,

chairman of the psychiatry department at Columbia and the lead investigator on a

federally sponsored clinical trial of schizophrenia medicines. " This drug may

turn out to be

not just a comparably good antipsychotic agent, but a better antipsychotic

agent. "

>

> Dr. Lieberman has not been involved with the development of the medicine and

does

not receive any payments or consulting fees from Lilly.

>

> The new drug also has the potential to be a blockbuster for Lilly. Medicines

for

schizophrenia and bipolar disorder are the fourth-best selling class of

medicines in the

United States, with sales of $12 billion in the United States and $18 billion

worldwide last

year.

>

> The troubled history of Zyprexa, another antipsychotic medicine from Lilly,

will lead

regulators and psychiatrists to scrutinize the new medicine closely for hidden

dangers, Dr.

Lieberman said. When it introduced Zyprexa in 1996, Lilly hailed it as a

breakthrough with

fewer side effects than older drugs. But Zyprexa causes severe weight gain, and

the

American Diabetes Association has linked it to diabetes. Internal Lilly

documents show

that the company played down Zyprexa's side effects, worrying they would hurt

sales.

>

> Despite that history, psychiatrists will be eager to see whether the new Lilly

medicine

works, since the existing drugs are of limited help for many patients. Existing

schizophrenia medicines, whether older drugs such as Thorazine or newer

medicines like

Zyprexa, all work by blocking the brain's dopamine receptors.

>

> But the new Lilly drug does not directly affect dopamine. Instead, it

modulates brain

activity through a different set of receptors. As a result, it has the potential

to be the first

truly novel treatment for schizophrenia since Thorazine was introduced 1954, Dr.

Lieberman and other researchers said.

>

> Lilly's new drug - which does not have a name yet and is referred to as

LY2140023 -

emerged from almost two decades of research by Dr. Darryle D. Schoepp, a

toxicologist

and pharmacologist who joined Lilly in 1988.

>

> For decades, psychiatrists have known that users of PCP, a street drug

sometimes called

angel dust, have symptoms nearly identical to those of people with

schizophrenia. By the

1980s, scientists had discovered that PCP blocked brain receptors that are

triggered by an

amino acid called glutamate. This led some companies and scientists to study

ways to

stimulate glutamate receptors as a treatment for schizophrenia.

>

> But the brain has many different kinds of glutamate receptors, and figuring

out how to

stimulate or block them in medically beneficial ways has proved complicated.

Instead of

focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating

the

action of glutamate receptors in the brain's prefrontal cortex, an area

responsible for

personality and learning.

>

> " This is a system that is so fundamental to the function of your brain that it

is quite

powerful, " said Dr. Schoepp.

>

> But because drugs that blocked dopamine had been the only successful

schizophrenia

treatments, many researchers viewed the glutamate pathway as unlikely to produce

useful

medicines, said Dr. P. Conn, director of the Vanderbilt University drug

discovery

program and an expert on glutamate research.

>

> Dr. Schoepp deserved praise for persuading Lilly to invest in a field that

appeared to be

a long shot, Dr. Conn said, adding, " He locked in very early. "

>

> As a result, Lilly appears to have a multiyear lead over its competitors in

glutamate

drugs, Dr. Conn said. Dr. Schoepp left Lilly in March to become the head of

neuroscience

research for Merck. Dr. Schoepp and Dr. , the president of Lilly

Research

Laboratories, both said that his departure would not hurt the development of

Lilly's new

medicine

>

> Dr. ph T. Coyle, a professor of psychiatry and neuroscience at Harvard

Medical

School, said the Lilly trial validated the theory that modulating glutamate

receptors might

control the symptoms of schizophrenia. Even if this drug fails in later trials,

companies

and scientists are likely to pursue glutamate research more aggressively, he

said.

>

> " When you see a company that comes up with something that's completely

different,

completely out of the box, that attracts attention, " Dr. Coyle said.

>

> Existing drugs are reasonably good at treating the hallucinations and

delusions of

schizophrenia. But they are far less effective at treating the so-called

negative symptoms

of the disease - the lack of motivation and emotion that leave many patients

unable to

work or have normal social relationships. The side effects of existing

medicines, which

affect nearly all patients, are also severe. Older drugs like Thorazine often

cause tics and

movement disorders, while newer medicines typically have fewer effects on

movement but

can cause weight gain and other metabolic changes.

>

> In the clinical trial whose results were reported yesterday, LY2140023 had

none of those

side effects and appeared to work about as well as Zyprexa at reducing symptoms.

In the

trial, which was conducted in Russia from August 2005 to June 2006, patients

were given

the experimental drug, Zyprexa or a placebo. About 100 patients received the

experimental medicine.

>

> For the drug to be approved, Lilly will need to replicate the results in

larger trials. This

month, Lilly will begin a trial with 870 patients to determine the most

effective dose of the

drug. That trial is expected to be complete in January 2009, and if it is

successful Lilly will

probably start a large Phase III trial that could cover at least 2,000 patients.

>

> " We have to confirm safety and efficacy with multiple studies, " Dr. of

Lilly said. He

said he did not want to offer a prediction of when Lilly might ask the Food and

Drug

Administration for approval. But he said Lilly intended to develop the drug

aggressively.

>

> " We are very actively working on this target and related targets because we

believe that

this mechanism is now validated, " he said.

>

> ###

>

>

>

[Guest guest]

Let me get this straight- PCP for schizophrenia? Like the PCP taken

by perps so jacked up on drug-induced adrenalin that they require

seven linebacker-sized cops to arrest and often die of drug-induced

coronaries in the process?

And glutamate receptors are involved in schizophrenia somehow? As in

the glutamate receptors which are screwed up by the MSG and other

substances in vaccines? Like the ones which were found to be messed

up in ASD children?

Is schizophrenia just late-onset autism at the end of the day?

Hormones hit, mingle with the body's toxic burden and regression

sets in?

Texjur, anyone?

>

> " By the 1980s, scientists had discovered that PCP blocked brain

receptors that are triggered by an amino acid called glutamate. This

led some companies and scientists to study ways to stimulate

glutamate receptors as a treatment for schizophrenia. But the brain

has many different kinds of glutamate receptors, and figuring out

how to stimulate or block them in medically beneficial ways has

proved complicated. Instead of focusing on the receptors blocked by

PCP, Dr. Schoepp concentrated on modulating the action of glutamate

receptors in the brain's prefrontal cortex, an area responsible for

personality and learning. "

> New Schizophrenia Drug Shows Promise in Trials

>

> by ALEX BERENSON

> Published: September 3, 2007

> In a clinical trial of about 200 patients, an experimental drug

from Eli Lilly reduced schizophrenia symptoms without the serious

side effects of current treatments, according to a paper published

yesterday in the journal Nature.

>

> The drug must still be evaluated on many more patients to test for

the possibility of side effects that have not yet emerged, and it is

at least three to four years from completing regulatory review.

>

> But schizophrenia researchers said the trial's results were

surprising and impressive, especially since the drug works in a

different way from existing antipsychotic medicines, all of which

have serious side effects, including substantial weight gain and

tremors.

>

> Lilly will begin a larger clinical trial for the drug this month.

If that trial confirms the results seen so far, the new drug could

mark a breakthrough in the treatment of schizophrenia - and open the

way to a broad new class of treatments for the disease.

Schizophrenia, a devastating mental illness that affects 1 percent

of adults, or about 2.5 million in the United States, usually begins

in the late teens or 20s and is marked by psychotic delusions as

well as social withdrawal and cognitive impairment.

>

> " This is potentially one giant step forward for patients, " said

Dr. Lieberman, chairman of the psychiatry department at

Columbia and the lead investigator on a federally sponsored clinical

trial of schizophrenia medicines. " This drug may turn out to be not

just a comparably good antipsychotic agent, but a better

antipsychotic agent. "

>

> Dr. Lieberman has not been involved with the development of the

medicine and does not receive any payments or consulting fees from

Lilly.

>

> The new drug also has the potential to be a blockbuster for Lilly.

Medicines for schizophrenia and bipolar disorder are the fourth-best

selling class of medicines in the United States, with sales of $12

billion in the United States and $18 billion worldwide last year.

>

> The troubled history of Zyprexa, another antipsychotic medicine

from Lilly, will lead regulators and psychiatrists to scrutinize the

new medicine closely for hidden dangers, Dr. Lieberman said. When it

introduced Zyprexa in 1996, Lilly hailed it as a breakthrough with

fewer side effects than older drugs. But Zyprexa causes severe

weight gain, and the American Diabetes Association has linked it to

diabetes. Internal Lilly documents show that the company played down

Zyprexa's side effects, worrying they would hurt sales.

>

> Despite that history, psychiatrists will be eager to see whether

the new Lilly medicine works, since the existing drugs are of

limited help for many patients. Existing schizophrenia medicines,

whether older drugs such as Thorazine or newer medicines like

Zyprexa, all work by blocking the brain's dopamine receptors.

>

> But the new Lilly drug does not directly affect dopamine. Instead,

it modulates brain activity through a different set of receptors. As

a result, it has the potential to be the first truly novel treatment

for schizophrenia since Thorazine was introduced 1954, Dr. Lieberman

and other researchers said.

>

> Lilly's new drug - which does not have a name yet and is referred

to as LY2140023 - emerged from almost two decades of research by Dr.

Darryle D. Schoepp, a toxicologist and pharmacologist who joined

Lilly in 1988.

>

> For decades, psychiatrists have known that users of PCP, a street

drug sometimes called angel dust, have symptoms nearly identical to

those of people with schizophrenia. By the 1980s, scientists had

discovered that PCP blocked brain receptors that are triggered by an

amino acid called glutamate. This led some companies and scientists

to study ways to stimulate glutamate receptors as a treatment for

schizophrenia.

>

> But the brain has many different kinds of glutamate receptors, and

figuring out how to stimulate or block them in medically beneficial

ways has proved complicated. Instead of focusing on the receptors

blocked by PCP, Dr. Schoepp concentrated on modulating the action of

glutamate receptors in the brain's prefrontal cortex, an area

responsible for personality and learning.

>

> " This is a system that is so fundamental to the function of your

brain that it is quite powerful, " said Dr. Schoepp.

>

> But because drugs that blocked dopamine had been the only

successful schizophrenia treatments, many researchers viewed the

glutamate pathway as unlikely to produce useful medicines, said Dr.

P. Conn, director of the Vanderbilt University drug

discovery program and an expert on glutamate research.

>

> Dr. Schoepp deserved praise for persuading Lilly to invest in a

field that appeared to be a long shot, Dr. Conn said, adding, " He

locked in very early. "

>

> As a result, Lilly appears to have a multiyear lead over its

competitors in glutamate drugs, Dr. Conn said. Dr. Schoepp left

Lilly in March to become the head of neuroscience research for

Merck. Dr. Schoepp and Dr. , the president of Lilly

Research Laboratories, both said that his departure would not hurt

the development of Lilly's new medicine

>

> Dr. ph T. Coyle, a professor of psychiatry and neuroscience at

Harvard Medical School, said the Lilly trial validated the theory

that modulating glutamate receptors might control the symptoms of

schizophrenia. Even if this drug fails in later trials, companies

and scientists are likely to pursue glutamate research more

aggressively, he said.

>

> " When you see a company that comes up with something that's

completely different, completely out of the box, that attracts

attention, " Dr. Coyle said.

>

> Existing drugs are reasonably good at treating the hallucinations

and delusions of schizophrenia. But they are far less effective at

treating the so-called negative symptoms of the disease - the lack

of motivation and emotion that leave many patients unable to work or

have normal social relationships. The side effects of existing

medicines, which affect nearly all patients, are also severe. Older

drugs like Thorazine often cause tics and movement disorders, while

newer medicines typically have fewer effects on movement but can

cause weight gain and other metabolic changes.

>

> In the clinical trial whose results were reported yesterday,

LY2140023 had none of those side effects and appeared to work about

as well as Zyprexa at reducing symptoms. In the trial, which was

conducted in Russia from August 2005 to June 2006, patients were

given the experimental drug, Zyprexa or a placebo. About 100

patients received the experimental medicine.

>

> For the drug to be approved, Lilly will need to replicate the

results in larger trials. This month, Lilly will begin a trial with

870 patients to determine the most effective dose of the drug. That

trial is expected to be complete in January 2009, and if it is

successful Lilly will probably start a large Phase III trial that

could cover at least 2,000 patients.

>

> " We have to confirm safety and efficacy with multiple studies, "

Dr. of Lilly said. He said he did not want to offer a

prediction of when Lilly might ask the Food and Drug Administration

for approval. But he said Lilly intended to develop the drug

aggressively.

>

> " We are very actively working on this target and related targets

because we believe that this mechanism is now validated, " he said.

>

> ###

>