Human phenylketonuria (PKU) results from phenylalanine hydroxylase (PAH) deficiency, and
represents one of the most common and extensively studied single-gene Mendelian disorders in
humans. Unfortunately, optimum clinical outcome demands lifelong dietary restriction through
adherence to an unpalatable and expensive artificial diet. Challenges in maintaining
traditional therapy lead to increasing phenylalanine (Phe) levels in patients as they
approach adulthood with an incumbent severe burden of psychosocial and intellectual
difficulties. The recent introduction of the new medication Sapropterin for treatment of PKU
has improved Phe control and dietary tolerance in some patients, but at enormous cost to
patients and insurers for the FDA designated orphan product. Thus, there is an unmet need for
novel therapies to correct PKU. PAH is almost exclusively expressed in the liver in humans.
The main objective of the current proposal is to examine the safety and efficacy of
hepatocyte transplantation in patients with PKU.