**6.4 Future therapies and new research areas**

Development of non-porcine enzyme replacement therapies is currently extended to new research areas including design, by direct molecular evolution, of human pancreatic lipase variants that display lipolytic activity at acidic pH higher than that of the native enzyme. Colin et al. (2008) investigated, first, the feasibility of altering the pH optimum of pancreatic lipase to improve its performances in the intestinal conditions of cystic fibrosis by sitedirected mutagenesis. Later, they demonstrated that directed molecular evolution approach combined to a sensitive screening strategy could be useful to improve pancreatic lipase activity at acidic pH. The authors showed that a single round of random mutagenesis was successful in identifying lipase variant with approximately 1.5-fold increased activity at low pH (Colin et al., 2010).

Future therapies may also include structuring food emulsions and creation of functional dietary lipids that are more effectively digested. This new area of research could substantially help patient suffering from pancreatic insufficiency with the design of specific more digestible or absorbable lipid sources. Hence, the addition of specific phospholipids able to enhance lipase activity in enzyme supplements or in formula would both increase lipase activity and, in parallel, enhance lipid nutrient absorption (Fieker et al., 2011).
