SBIR-STTR Award

A new, innovative and patented lipid matrix composed of lysophosphatidylcholine (LPC), monoglycerides (MG) and fatty acids (FA) is readily absorbed, improving the clinical well-being of cystic fibrosis (CF) patients who have compromised fat absorption in spite of supplemental pancreatic enzyme therapy. The acceptability of this innovative lipid matrix by the CF community requires a product having palatable taste characteristics. We are proposing an innovative concept for resolving the palatability challenge. Although some of the individual components can produce undesirable taste, the stabilization of these components within the matrix per se should greatly improve palatability. The polar head groups of the organized lipid matrix can be intramolecularly stabilized by water and/or metal ions yielding a discreet complex having acceptable taste characteristics. The structural integrity of intramolecularly stabilized lipid matrices will be evaluated using a range of physical methodologies (differential scanning calorimetry, x-ray diffraction, phosphorus NMR, freeze fracture electron microscopy, polarizing light microscopy, and viscosity). Those lipid matrices having the greatest intramolecular stabilization will be screened for palatability and selected lipid matrix formulations will be tasted in blind tests using CF patients. Thus, defining the intramolecular stabilization and structural integrity of the lipid matrix to produce desirable taste profiles represent innovative research

Individuals with cystic fibrosis (CF) and pancreatic insufficiency (PI) are prone to fat malabsorption, putting them at risk for caloric, essential fatty acid, and choline deficiency, which, in turn, may lead to growth failure and a poorer clinical course. Many subjects with CF have essential fatty acid deficiency, characterized by decreased levels of linoleic acid and an increased triene/tetraene ratio, and an associated choline deficiency. As a key membrane phospholipid, choline is required for methyl metabolism, cholinergic neurotransmission, transmembrane signaling, lipid cholesterol transport and metabolism. Choline deficiency is associated with liver disease, apoptosis, steatosis, as well as brain and visual development abnormalities. In a previous randomized control trial, supplementation with LYM-X-SORB(TM), an organized lipid matrix containing lysophosphatidylcholine (LPC) monoglycerides, and triglycerides, has been shown to improve fatty acid status and vitamin E and retinol binding protein levels over a 12-month period and to improve both growth and pulmonary function status over 18 months in subjects with CF. We propose to conduct a randomized placebo-controlled double-blinded study to evaluate the effectiveness of the next generation LYM-X-SORB(TM) with improved palatability and mixing characteristics, on fatty acid and choline status of 78 children, ages 6.0 to 17.9 years, with CF and PI. We propose that essential fatty acid status (linoleic acid levels, triene/tetraene ratio) and choline status (phosphadytlcholine/ phosphatidytlethanolamine (PC/PE) ratio) will be normalized after 12 mos of supplementation with LYM-X-SORB(TM) in subjects receiving LYM-X-SORB(TM) (n=39) compared to those receiving placebo (n=39). We will also explore whether LYM-X-SORB(TM) supplementation will improve fat soluble vitamin status, bile composition, incidence of fatty liver, inflammatory cytokines, resting energy expenditure and respiratory quotient over 12 mos and improve pulmonary function, growth status, body composition and overall health status over 18 mos. Subjects will be recruited from five Cystic Fibrosis Centers and have four major protocol visits to CHOP (baseline, 3, 12, and 18 mos), and one visit at their home Center (6 mos). Our objective is to determine if LYM-X-SORB(TM) can be used as an acceptable, effective, supplement to correct the metabolic and physiological abnormalities associated with fat malabsorption in subjects with CF, the most commonly inherited genetic disease in Caucasians