Hereditary inclusion body myopathy: single patient response to GNE gene Lipoplex therapy.

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.

Preventive health care among community-dwelling persons with spinal cord injury.

OBJECTIVE: To describe preventive health examinations/tests and behaviors of persons with traumatic spinal cord injury (SCI). DESIGN: Survey. SETTING: SCI clinic and telephone contact. PARTICIPANTS: A total of 59 persons ≥18 years of age with traumatic SCI. INTERVENTION: None. MAIN OUTCOME MEASURES: Preventive health examinations/tests and reason for not receiving an examination or test. RESULTS: Preventive health tests/examinations received within the past year: flu vaccination (40.7%); eye examination (50.8%); dental check-up (64.4%); physical examination (61.0%); vitamin D level (56.0%); cholesterol level (25.4%); and blood glucose level (39.0%). For men, 20.0% had a prostate examination and 20.0% had a colonoscopy. For women, 25.0% had a pelvic examination and 62.5% had a mammogram in the past 2 years. The most endorsed reasons for not getting an examination/test was "It was my choice" followed by "No one told me to have [examination/test]." The number of years injured had an inverse relationship with having vitamin D level checked (r = -334) and had a positive association with having serum cholesterol level checked (r = .474). CONCLUSION: Preventive health tests and examinations in the SCI population are being obtained at about the same rate as in the U.S. population with some exceptions (ie, cholesterol level check, colonoscopy, and pelvic examination); however, the rates are far from the goals of Healthy People 2020. Primary care and SCI clinicians should be proactive in educating their patients about the importance of preventive health, especially those who have been injured for a long time.

Hereditary inclusion body myopathy: single patient response to intravenous dosing of GNE gene lipoplex.

Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult-onset myopathy due to mutations in the GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene. Affected patients have no therapeutic options. We have previously demonstrated in preclinical testing the ability to safely correct GNE gene function through liposomal delivery of the wild-type GNE gene. Results were verified in a single patient treated by intravenous infusion of GNE gene lipoplex. A single patient (patient 001) with severe HIBM treated with a compassionate investigational new drug received seven doses of GNE gene lipoplex via intravenous infusion at the following doses: 0.4, 0.4, 1.0, 4.0, 5.0, 6.0, and 7.0 mg of DNA. GNE transgene expression, downstream induction of sialic acid, safety, and muscle function were evaluated. Transient low-grade fever, myalgia, tachycardia, transaminase elevation, hyponatremia, and hypotension were observed after infusion of each dose of GNE gene lipoplex. Quadriceps muscle expression of the delivered GNE, plasmid, and RNA was observed 24 hr after the 5.0-mg dose and at significantly greater levels 72 hr after the 7.0-mg infusion in comparison with expression in quadriceps muscle immediately before infusion. Sialic acid-related proteins were increased and stabilization in the decline of muscle strength was observed. We conclude that clinical safety and activity have been demonstrated with intravenous infusion of GNE gene lipoplex. Further assessment will involve a phase I trial of intravenous administration of GNE gene lipoplex in individuals with less advanced HIBM with more muscle function.