Project Description:
CM-AT is a lipid-encapsulated pancreatic enzyme concentrate (PEC) designed to release chymotrypsin and other proteases in the proximal small intestine without extreme degradation. CM-AT is a novel formulation in that it allows high protease delivery without an enteric coating and that it is designed for delivery to the proximal small intestine. The construction of the formulation as a sprinkle in a single-unit dose sachet coupled with the small particle size of enzyme contained in the sprinkle allows for an easy dispersion in food as well as the ability to mask the presence of the enzyme in the food. The lipid encapsulation presents a water barrier and retards the degradation of the biologically active enzymes and a targeted delivery can be achieved. The intended indication of CM-AT is for the treatment of irritability and social withdrawal, in children ages 3-8 who have autism.
Curemarks findings indicate that a large subset of children with autism have an endogenous lack of chymotrypsin, as expressed by low fecal chymotrypsin levels. Chymotrypsin is a serine protease that cleaves only the essential amino acids tryptophan, phenylalanine, leucine, and methionine, and the conditionally essential amino acid tyrosine. It is hypothesized that if there is an underlying defect in the digestion of dietary proteins, it would contribute to a deficiency in essential and semi-essential amino acids. This would leave the child unable to synthesize new proteins. Proteins such as neurotransmitters and other essential proteins needed for key bodily functions may not be able to be produced by the body due to a lack of essential amino acids. A partial or complete lack of protein digestion could further lead to allergy and/or other digestive dysfunctions. Tryptophan and phenylalanine are involved in and necessary for the synthesis of serotonin and dopamine respectively. Methionine serves as the initiation codon for all RNA translation and leucine is necessary to stimulate muscle synthesis. A dearth of these amino acids can result potentially in a decrease in their intended activity.
Research conducted by Curemark has indicated that digestive enzyme therapy with CM-AT may lead to increased neurological function and a concomitant reduction in autistic and gastrointestinal symptoms. The enzyme therapy may also reduce the potential for undigested proteins to become allergens or promote the growth of pathogenic agents, thereby reducing immunopathologic effects.
PEP (Pancreatic Enzyme Products) pharmaceutical products such as CM-AT have been used for over 40 years in humans and have been recognized as safe in terms of toxicology and pharmacology both in humans and animals. The two components of CM-AT have been previously classified as Generally Recognized as Safe (GRAS) by the Food and Drug Administration.
Double-blind randomized placebo-controlled study of CM-AT in 180 children demonstrated that CM-AT was safe and well tolerated in children who were diagnosed with autism and who had low/pathological levels of fecal chymotrypsin. Study 101 and the open label continuation Study 102 demonstrated that chymotrypsin was replaced through the administration of CM-AT in those who received the drug. This finding was statistically significant over those on placebo. Fecal chymotrypsin levels were utilized as a biomarker inclusion for those entering the 101 trial. Determination of the final level of replacement and the benefits to those who are biomarker negative will be examined in this study.
