Therapeutic liver repopulation for phenylketonuria

Cary Harding, K. M. Gibson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Problems with long-term dietary compliance in phenylketonuria (PKU) necessitate the development of alternative treatment approaches. Therapeutic liver repopulation with phenylalanine hydroxylase (PAH)-expressing cells following hepatocyte or haematopoietic stem cell transplantation has been investigated as a possible novel treatment approach for PKU. Successful therapeutic liver repopulation requires both a stimulus for liver regeneration at the time of cell transplantation and a selective growth advantage for the PAH+ donor cells. Unfortunately, wildtype PAH+ hepatocytes do not enjoy any growth advantage over PAH- cells. Successful correction of hyperphenylalaninemia following therapeutic liver repopulation has been accomplished only in an animal model that yields a selective advantage for the donor cells. Haematopoietic stem cell (HSC)-mediated therapeutic liver repopulation has not been reported in any hyperphenylalaninemic system, and the success of HSC-mediated liver repopulation for PKU may be limited by the slow kinetics of this approach. If therapeutic liver repopulation is to be employed successfully in humans with PKU, an effective method of providing a selective growth advantage for the donor cells must be developed. If this can be achieved, liver repopulation with 10-20% wild-type hepatocytes will likely completely normalize Phe clearance in individuals with PKU.

Original languageEnglish (US)
Pages (from-to)681-687
Number of pages7
JournalJournal of Inherited Metabolic Disease
Volume33
Issue number6
DOIs
StatePublished - Dec 2010

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Phenylketonurias
Phenylalanine Hydroxylase
Liver
Hepatocytes
Hematopoietic Stem Cells
Therapeutics
Growth
Liver Regeneration
Hematopoietic Stem Cell Transplantation
Cell Transplantation
Animal Models

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Therapeutic liver repopulation for phenylketonuria. / Harding, Cary; Gibson, K. M.

In: Journal of Inherited Metabolic Disease, Vol. 33, No. 6, 12.2010, p. 681-687.

Research output: Contribution to journalArticle

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