Repligen Corporation (Nasdaq: RGEN) reported today the publication of a study in the journal Neuroscience which demonstrates that an injection of the hormone secretin specifically activates neurons in the amygdala in rats, a part of the brain which has previously been implicated in the social interaction deficits of autism. This is the first published evidence that intravenously administered secretin can modulate the activity of the brain. Several studies in other laboratories have previously established that people with autism do not show normal activation of the amygdala when engaged in social interactions such as recognizing emotions from facial expressions. The identification of the amygdala as the primary site of action of secretin provides a potential mechanism by which secretin may affect the social interaction deficits of autism. Secretin is currently being evaluated by the Company for the improvement of reciprocal social interaction in children with autism; however, to date there has been no biological model for how secretin, better known as a gastrointestinal hormone, may affect the brain.

The article entitled "A Secretin Intravenous Infusion Activates Gene Expression in the Central Amygdala of Rats" (Neuroscience, 188 (2003) 881-888) describes experiments in which activity in the brain was measured after a single intravenous injection of secretin. Neuronal activation was evaluated 1-4 hours following administration of secretin, a related peptide or a placebo. The brain tissue was fixed and stained for Fos, a readily measured and well-established marker of neuronal activity. Prominent activation of the central amygdala was observed after two hours in secretin-treated rats that was significantly greater than was observed in placebo-treated rats (p<0.001). The research was carried out by Repligen scientists in collaboration with researchers at the VA Medical Center in Boston and Harvard Medical School.

"This study demonstrates that secretin specifically activates a part of the brain involved in social interaction and known to have an altered pattern of activity in autism," stated Walter C. Herlihy, President and CEO of Repligen. "The finding that secretin modulates amygdala activity suggests that it may have an impact on autism as well as on other neurological diseases characterized by social interaction deficits."

Activation in the amygdala has been confirmed by a second group of academic researchers who are collaborating with Repligen scientists to further understand the pathway of amygdala activation. Additional data on the mechanism by which secretin activates the amygdala will be presented this month at Digestive Disease Week in Orlando, FL.

The Amygdala and 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. Although neuropathological and imaging studies have revealed abnormalities in several regions of the brain in autism, a lack of activation of the amygdala is recognized as an important correlate of the social deficits of autism.

The role of the amygdala in social interaction has been studied in both normal and autistic patients using various neuroimaging tools. Studies using functional magnetic resonance imaging (fMRI) have established an activation of the amygdala when processing and responding to social stimuli. Reduced activation of the amygdala in patients with autism has been documented using fMRI with particular impairment noted in their ability to respond to facial expressions of fear, to perceive eye-gaze direction and to establish recall memory for faces. Other studies indicate that patients with either surgical or congenital amygdala damage show similar symptoms. These data suggest that dysfunction of the amygdala is important in autism.

In November of 2002 researchers from the Brain Imaging Center at McLean Hospital presented functional magnetic resonance imaging data showing that an intravenous injection of secretin in healthy adults potentiated the activity of the amygdala when viewing pictures of emotional facial expressions.

Repligen is currently enrolling children aged 2 years 8 months to 4 years 11 months with moderate to severe symptoms of autism into two Phase 3 clinical trials. Each patient is comprehensively evaluated at baseline, receives six injections of RG1068 (synthetic human secretin) or a placebo over 18 weeks, and is then reevaluated for improvements in the symptoms of autism. The trials are currently being carried out at approximately 20 medical centers in the United States. Information concerning participation in the Phase 3 clinical trials may be found on www.autismtrial.com.

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(TM) and SecreFlo(TM), the profits from which will be used to support the development of our proprietary products. rProtein A(TM) is a consumable reagent used by the pharmaceutical industry to produce a class of drugs called monoclonal antibodies and SecreFlo(TM), secretin for injection, is marketed to gastroenterologists for pancreatic assessment and for use during a gastrointestinal procedure called ERCP. 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.

This Article has been submitted by the Jeremy's Prophecy Dot Com team for informational and educational purposes. Jeremy's Prophecy Dot Com is a website dedicated to telling the story of Jeremy Jacobs, a character in the novel, Jeremy's Prophecy Dot Com.