Liver Cell Transplant for Phenylketonuria
Summary
The purpose of this research study is to determine whether partial irradiation of the liver and liver cell transplantation can reduce the need for dietary and medical management or could possibly eliminate the need for a special diet and medications to treat this disease for patients with phenylketonuria (PKU) by normalizing phenylalanine levels in the body. Phenylalanine (Phe) is a substance needed in the body that can only be obtained from the foods the investigators eat. People with PKU cannot get rid of Phe in their body. Large amounts of Phe can cause problems, such as deterioration of mental function. At the present time, liver cell transplants are experimental and have been done in only a limited number of human subjects.
Description
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 determine the feasibility of hepatocyte transplantation to correct the biochemical (and ultimately, clinical) features of PKU.
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Phenylketonuria
Intervention
Preparative Radiation Therapy, Hepatocyte Transplant, Immunosuppression, Liver Evaluation
Location
Children's Hospital of Pittsburgh of UPMC
Pittsburgh
Pennsylvania
United States
15201
Status
Recruiting
Source
University of Pittsburgh
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01465100
- Information obtained from ClinicalTrials.gov on August 02, 2012
Medical and Biotech [MESH] Definitions
Transplantation Conditioning
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
Hepatocyte Nuclear Factor 1-beta
A hepatocyte nuclear factor that is closely related to HEPATOCYTE NUCLEAR FACTOR 1-ALPHA but is only weakly expressed in the LIVER. Mutations in hepatocyte nuclear factor 1-beta are associated with renal CYSTS and MATURITY-ONSET DIABETES MELLITUS type 5.
Neoadjuvant Therapy
Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.
Hepatocyte Nuclear Factors
Hepatocyte nuclear factors are a family of evolutionarily conserved transcription factors that are preferentially expressed in HEPATOCYTES. They play important roles in liver-specific transcription and are critical for CELL DIFFERENTIATION and METABOLISM.
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