Brain Imaging Study of Secretin

[Guest guest]

[forwarded from the CAN Alert Newsletter]

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McLean Hospital and Repligen Announce Results of Brain Imaging Study of

Secretin -- Secretin is Active in a Brain Region Implicated in Autism

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Story Filed: Friday, November 01, 2002 8:00 AM EST

BELMONT, Mass., and WALTHAM, Mass., Nov 1, 2002 /PRNewswire-FirstCall via

COMTEX/ -- Researchers from the Brain Imaging Center at McLean Hospital and

Repligen Corporation (Nasdaq: RGEN) reported today the results of a clinical

trial designed to assess the neurological activity of secretin by functional

magnetic resonance imaging (fMRI). The results demonstrate for the first

time in humans that secretin is active in the central nervous system and

that it potentiates activity in the amygdala, a region of the brain involved

in social integration and implicated in autism. The findings were presented

today by Deborah Yurgelun-Todd, Ph.D., of McLean Hospital, the study's

Principal Investigator, at the International Meeting for Autism Research, a

satellite meeting of the Society for Neuroscience.

" Our results demonstrate for the first time that secretin is a neuroactive

peptide in humans and that it acts on a brain region known to be important

for social interaction, " stated Yurgelun-Todd, Director of Cognitive

Neuroimaging at the Brain Imaging Center at McLean Hospital. " These findings

suggest that secretin may have a role in modulating social behavior in

humans. "

The study was a double-blind, placebo-controlled clinical trial in 12

healthy men. Each subject was presented with a series of pictures of faces

with either a neutral, happy or fearful facial expression to establish a

baseline response. Following an injection of either secretin or a placebo,

the subjects were again presented with the series of facial expressions.

Throughout the experiment, the activation of the amygdala was recorded with

MRI. There was a significant activation (p=0.001) of the right amygdala by

secretin when the subjects viewed pictures of a fearful face compared to

both the placebo group and the baseline response to the pictures in the

secretin group. By contrast, there was no difference in amygdala activation

when subjects viewed pictures of neutral or happy faces. Failure to activate

the amygdala when viewing fearful faces is a characteristic of people with

autism and patients with amygdala damage. The current study was initiated as

part of ongoing research efforts to understand secretin as a neurologically

active peptide. Repligen previously reported a finding that treatment of

rats with secretin specifically activates the neurons in the amygdala.

Repligen is currently developing secretin for autism in a Phase 3 clinical

trial program.

" These studies show that secretin is active in a part of the human brain

involved in social interaction and potentiates its activity during a social

task known to be difficult for people with autism, " stated Walter C.

Herlihy, Ph.D., President and Chief Executive Officer of Repligen

Corporation. " These data provide a plausible biological mechanism for the

improvements in social interaction we observed in our Phase 2 clinical

trial. "

The Amygdala and the Social Deficits of Autism

The amygdala is part of a complex neural system that is critical for

ascribing emotional value to stimuli and influencing affective

responsiveness and emotional learning. One of the core deficits of autism is

impaired reciprocal social interaction, including eye contact, joint

attention and an inability to deduce the mental states of others from facial

expressions. Reduced activation of the amygdala in patients with autism has

been documented using fMRI with specific impairment noted in their ability

to respond to facial expressions of fear. Other studies indicate that

patients with either surgical or congenital amygdala damage show similar

face recognition defects. Lack of activation of the amygdala is recognized

as an important correlate of the social deficits of autism.

Repligen's President and CEO Walter C. Herlihy, Ph.D. also presented data

from its Phase 2 clinical trial. The Phase 2 study evaluated three

administrations of secretin or a placebo in 126 patients aged 3 years to 6

years 11 months with moderate to severe symptoms of autism and

gastrointestinal disorders. The primary finding of the Phase 2 clinical

trial was that younger children, 3 and 4 year olds, showed improvements in

reciprocal social interaction as judged by a standardized clinical

instrument for the assessment of autistic symptoms. Repligen is currently

conducting a Phase 3 clinical trial of secretin for the improvement of

reciprocal social interaction in young children with autism.

About McLean Hospital

McLean Hospital maintains the largest research program of any private, U.S.

psychiatric hospital. It is the largest psychiatric teaching facility of

Harvard Medical School, an affiliate of Massachusetts General Hospital and a

member of Partners HealthCare. The Brain Imaging Center at McLean is one of

the largest imaging centers in the world, actively engaged in clinical

research studies of brain function. Researchers at McLean were part of the

team that first identified regional abnormalities in brain activation in

patients with schizophrenia and in normal aging, as well as regional changes

in blood flow and metabolism in patients with Alzheimer's disease.

About Repligen Corporation

Repligen Corporation is a biopharmaceutical company committed to being the

leader in the development of new drugs for pediatric developmental disorders

including autism, immune and metabolic disorders. Repligen has a specialty

pharmaceuticals business comprised of rProtein A and SecreFlo, the

profits from which will be used to support the development of our

proprietary products. rProtein A is a consumable reagent used by the

pharmaceutical industry to produce a class of drugs called monoclonal

antibodies and SecreFlo, secretin for injection, is marketed to

gastroenterologists for pancreatic assessment. Repligen's corporate

headquarters are located at 41 Seyon Street, Building #1, Suite 100,

Waltham, MA 02453. Additional information may be requested from

www.repligen.com.