Thursday, June 13, 2013
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Mouse studies suggest TPO
mimetics or CD110 agonists could help enhance engraftment of hematopoietic
stem cells (HSCs) following bone marrow transplant (BMT). In mice with
ablated bone marrow, CD110 deficiency or an anti-CD110 antibody decreased
megakaryocyte recruitment to HSC niches and subsequent osteoblast expansion
compared with normal CD110 expression or no treatment, respectively. In mouse
models for BMT, TPO pretreatment increased HSC engraftment compared with no
pretreatment. Next steps could include testing marketed TPO receptor agonists
in mouse models for BMT. GlaxoSmithKline
plc and Ligand
Pharmaceuticals Inc. market Promacta
a small molecule TPO receptor agonist, to treat thrombocytopenia and
idiopathic thrombocytopenic purpura (ITP). The compound is under regulatory
review to treat HCV and is in Phase III testing to reduce the need for
platelet transfusion in patients with thrombocytopenia and chronic liver disease who are undergoing elective
Inc. and Kyowa
Hakko Kirin Co. Ltd. market Nplate
a recombinant fusion protein containing a pair of TPO receptor-binding
domains, to treat ITP.
Co. Ltd.'s avatrombopag (E5501),
an oral TPO receptor agonist, is in Phase III testing to treat ITP.
Published online June 13, 2013
Patent and licensing status
Olson, T.S. et al. Blood;
published online May 10, 2013;
Contact: Edwin M. Horwitz, Children's Hospital of Philadelphia,
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