Gene therapy for platelet disorders: studies with Glanzmann's thrombasthenia. J Thromb Haemost 2003 Nov;1(11):2300-11
Date
11/25/2003Pubmed ID
14629461DOI
10.1046/j.1538-7836.2003.00476.xScopus ID
2-s2.0-4444281228 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
Current research aimed at correcting platelet defects are designed to further our knowledge in the use of hematopoietic stem cells for gene therapies of hemorrhagic disorders. Information gained from these studies may be directly applicable to treatment of disorders affecting platelets (e.g. Glanzmann's thrombasthenia, Bernard Soulier syndrome, gray platelet syndrome, and von Willebrand disease) as well as other disorders affecting distinct hematopoietic cell lineages. This work specifically addresses three questions: (i) can bone marrow stem cells be given sufficient genetic information to induce abnormal megakaryocytes to synthesize transgene products that help newly formed platelets to participate in normal hemostasis? (ii) can the newly synthesized receptor be maintained as a platelet-specific protein at therapeutic levels for a reasonable period of time? and (iii) will newly expressed proteins be tolerated by the immune system or become a target for B- and T-cell mediated immunity resulting in the premature destruction and clearing of the genetically altered megakaryocytes and platelets? Answers to these questions should indicate the feasibility of targeting platelets with genetic therapies that will in turn enable better management of patients with inherited bleeding disorders. The long-range benefit of this research will be an improved understanding of the regulation of protein expression during normal megakaryocytopoiesis, and the accumulation of additional scientific knowledge about normal platelet function and the way in which platelets and other cells recognize and interact with each other.
Author List
Wilcox DA, White GC 2ndAuthors
Gilbert C. White MD Professor in the Medicine department at Medical College of WisconsinDavid A. Wilcox PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelet Disorders
Genetic Therapy
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Immune Tolerance
Megakaryocytes
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombasthenia