Clinical Trial: The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Brief Summary: This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.
Detailed Summary:
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, thrombosis, and variable cytopenia. It can be associated with significant morbidity including acute kidney failure, cerebral infarction, mesenteric infarction, Budd-Chiari syndrome, aplastic anemia, and leukemic transformation. The average survival time from diagnosis is 15 years.
PNH is an acquired clonal disorder of the hematopoietic stem cell. Two distinct populations of hematopoietic cells exist in each PNH patient: one non-clonal population of normal cells, and one clonal population of PNH cells. The clonal population of PNH cells is identified by a mutation in the PIG-A gene that results in absence of the glycophosphatidylinositol (GPI) anchor of several surface proteins. Consequently, these surface proteins are unable to perform their functions on the cell surface. Deficiency of two of these surface proteins, CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis) that prevent complement mediated destruction, have been shown to underlie the clinical presentation of PNH. Identifying the mutation causing the predominant clones may help us better understand the molecular biology of PNH. When this is accomplished, new therapies to control and eventually cure the disease can be designed.
In addition, we propose to determine the function of PrP in human hematopoietic stem cells. PrP is a glycoprotein attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In PNH, a disorder whose pathogenesis lies in the absence of GPI anchors, PrP expression is reduced in monocytes and granulocytes from the PNH clone.
Sponsor: University of Utah
Current Primary Outcome: Identify the mutation causing the predominant clones through analysis of extracted DNA/RNA from erythroid colonies [ Time Frame: After sample is obtained ]
Original Primary Outcome: Determine if Prion Protein functions in long term hematopoietic stem cell renewal or proliferation in humans. [ Time Frame: After sample is obtained ]
Current Secondary Outcome:
- Reconfirmation of PrP expression in human granulocytes, hematopoietic progenitors and stem cells [ Time Frame: After sample is obtained ]
- Analysis of PrP function in human long term hematopoietic stem cells [ Time Frame: After sample is obtained ]
Original Secondary Outcome: Reconfirm the decreased Prion Protein expression in the peripheral blood and bone marrow of PNH patients [ Time Frame: After sample is obtained ]
Information By: University of Utah
Dates:
Date Received: July 23, 2008
Date Started: May 2006
Date Completion:
Last Updated: August 5, 2011
Last Verified: August 2011
