Five separate research groups presented results of studies on the use of secretin in autistic children .

“These five studies provide important data relevant to the development of secretin in autism and expand the effort to understand gastrointestinal symptoms in these patients and their potential connection to the core symptoms of autism,” stated Walter C. Herlihy, Ph.D., President and CEO of Repligen, the company which holds the patent on synthetic secretin. He adds that “there may be a subset of children whose gastrointestinal or behavioral symptoms are particularly responsive to secretin.”

One study was entitled “Secretin Improves Intestinal Permeability in Autistic Children”:

* The authors note that prior studies have reported that a significant fraction of autistic children suffer from a form of intestinal dysfunction characterized by elevated intestinal permeability (“leaky gut”).

* This study examined the intestinal permeability of 25 autistic children and measured the changes following a single secretin injection.

* Initially, 76% (19/25) of the patients had abnormally elevated intestinal permeability prior to treatment.

* The effect of secretin on intestinal permeability in autistic children was evaluated in a double-blind, placebo-controlled study which included one placebo and one porcine (pig derived) secretin injection.

* Urine samples showed a decrease in permeability in 13 out of the 20 patients (65%).

The authors concluded that a significant percentage of autistic children have abnormal intestinal permeability which may be improved by a single secretin injection.

Another study was entitled “Evaluation of Gastrointestinal Symptoms in Autistic Children Before and Following Secretin Infusion”:

* This study enrolled 20 autistic children (18 male), 3-6 years old with a confirmed diagnosis of autism, and reported GI symptoms.

* Clinical observations confirmed parental reports that 16/20 (80%) of the children have at least 2 loose stools during a 24- hour period.

* A 3 CU/Kg dose of porcine (pig derived) secretin was then administered.

* At the one-week follow-up visit, 7/16 (44%) of children with previously noted diarrhea brought diapers containing formed stool to the clinic.

* A majority of the parents (15/20) also reported fewer and more formed stools during the 5-week follow-up period.

* The authors also recorded changes in expressive language, and found no statistically significantdifference in language between baseline and follow-up evaluations at 1, 2, 3 and 5 weeks post-treatment, despite the fact that 83% of parents reported moderate to significant language improvement following secretin.

* The authors conclude that potential pancreatic dysfunction and/or the role of secretin in GI symptoms in autism require further investigation.

Another study was entitled “Synthetic Human Secretin in the Treatment of Pervasive Developmental Disorders”:

* This double-blind, placebo controlled study assessed the efficacy of synthetic human secretin in the treatment of pervasive developmental disorders.

* Thirty autistic children aged 2 to 10 were followed for 12 weeks after a single infusion of secretin or a placebo.

* Children were randomly assigned to one of three groups to receive either high dose (0.4 mg/kg) secretin, low dose (0.2 mg/kg) secretin, or placebo.

* The average scores on the using various rating scales, including the Childhood Autism Rating Scale, Vineland Adaptive Behavior Scales, Gilliam Autism Rating Scale, and the Preschool Language Scale-3, improved over time in all three treatment groups.

* Children with the greater severity of autistic symptoms showed the greatest improvement at 6 and 12 weeks as the dosage of secretin increased.

* Single dose secretin therapy was generally ineffective in children who presented with mild ormoderate levels of autism.

The authors conclude that secretin was somewhat more effective when the symptoms of autism were more severe, and this effectiveness was greater with higher dose secretin therapy.

Another study was entitled “Safe Use of Intravenous Secretin in Autistic Children”:

* The safety of secretin was assessed in 34 autistic children for immediate reactions and post-injection side effects within the 6 weeks following two doses of porcine (pig derived) secretin.

* There were no immediate life threatening side effects.

* Analysis of blood samples showed that 25 of the 34 had low secretin levels just before the first dose.

* A dramatic change in their sociability was noted by parents and therapists/doctors in 4 of the 34 (12%) patients, all 4 of whom had low baseline secretin levels and a positive anti-gliadin IgG.

The authors conclude that two doses of intravenous secretin is safe to use in children provided that they are observed for at least 1 hour and that a small subset of children who are anti-gliadin IgG positive and have low secretin levels have a greater chance for significant improvement in their autistic symptoms.

Another study was entitled “Analysis of Compounds in the Urine of Autistic Children with HPLC and Mass Spectrometry”:

* The authors note that previous studies have reported opioid peptides in urine and altered amounts of some urinary metabolites.

* Urine samples were collected from 40 autistic children aged 3-12 and 44 healthy children.

* The most significant difference in the two groups was a significant fraction (47%) of the autistic patients with undetectable levels of 7- methylxanthine in their urine.

* In this double-blind, placebo-controlled, crossover clinical study in 20 children the effect of placebo vs. secretin was evaluated on urinary metabolites.

* Therewas a significant increase in urinary 7-methylxanthine following secretin which was not observed following placebo.

* Four autistic children who had no detectable levels of 7- methylxanthine at the beginning of the study showed an increase of greater than 100-fold following secretin.

The authors concluded that additional studies are warranted to determine if a lack of urinary 7-methylxanthine defines a subset of autistic children who may be more responsive to secretin.

Repligen is currently conducting a Phase 2, placebo-controlled clinical trial of three doses of secretin in young children with autism at five sites in the United States.