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Hereditary inclusion body myopathy: single patient response to GNE gene Lipoplex therapy
Author(s) -
Nemunaitis Gregory,
Maples Phillip B.,
Jay Chris,
Gahl William A.,
Huizing Marjan,
Poling Justin,
Tong Alex W.,
Phadke Anagha P.,
Pappen Beena O.,
Bedell Cynthia,
Templeton Nancy S.,
Kuhn Joseph,
Senzer Neil,
Nemunaitis John
Publication year - 2010
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1450
Subject(s) - sialic acid , medicine , myopathy , transgene , genetic enhancement , skeletal muscle , pharmacology , downregulation and upregulation , gene , gene delivery , cancer research , biology , genetics
Background Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult onset myopathy. It is characterized by mutations of the GNE (UDP‐ N ‐acetylglucosamine 2‐epimerase/ N ‐acetylmannosamine kinase) gene. Afflicted patients have no therapeutic options. In preclinical testing, we have previously demonstrated the ability to correct GNE gene function and the safety of delivery of wild type GNE gene using a liposomal delivery vehicle. Methods A single patient (subject #001) with severe HIBM treated by compassionate investigational new drug received four doses of GNE gene Lipoplex via intramuscular injection. GNE transgene expression, downstream induction of sialic acid, safety and muscle function were evaluated. Results Significant durable improvement in locoregional skeletal muscle function was observed in the injected left extensor carpi radialis longus of #001 in correlation with GNE transgene upregulation and local induction of sialic acid. Other than transient low grade fever and pain at the injection site, no significant toxicity was observed. Conclusions Proof of principle for manufacturing of ‘clinical grade’ GNE gene Lipoplex, clinical safety and activity are demonstrated with GNE gene Lipoplex. Further assessment will involve intravenous administration and subsequent phase I trial involving additional but less severely afflicted HIBM patients. Copyright © 2010 John Wiley & Sons, Ltd.