Dataset Information

Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.

ABSTRACT: Phosphorodiamidate morpholino oligonucleotide (PMO)-mediated control of the alternative splicing of the chloride channel 1 (CLCN1) gene is a promising treatment for myotonic dystrophy type 1 (DM1) because the abnormal splicing of this gene causes myotonia in patients with DM1. In this study, we optimised a PMO sequence to correct Clcn1 alternative splicing and successfully remedied the myotonic phenotype of a DM1 mouse model, the HSALR mouse. To enhance the efficiency of delivery of PMO into HSALR mouse muscles, Bubble liposomes, which have been used as a gene delivery tool, were applied with ultrasound exposure. Effective delivery of PMO led to increased expression of Clcn1 protein in skeletal muscle and the amelioration of myotonia. Thus, PMO-mediated control of the alternative splicing of the Clcn1 gene must be important target of antisense therapy of DM1.

SUBMITTER: Koebis M

PROVIDER: S-EPMC3718203 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.

Koebis Michinori M Kiyatake Tamami T Yamaura Hiroshi H Nagano Kanako K Higashihara Mana M Sonoo Masahiro M Hayashi Yukiko Y Negishi Yoichi Y Endo-Takahashi Yoko Y Yanagihara Dai D Matsuda Ryoichi R Takahashi Masanori P MP Takahashi Masanori P MP Nishino Ichizo I Ishiura Shoichi S

Scientific reports 20130101

Phosphorodiamidate morpholino oligonucleotide (PMO)-mediated control of the alternative splicing of the chloride channel 1 (CLCN1) gene is a promising treatment for myotonic dystrophy type 1 (DM1) because the abnormal splicing of this gene causes myotonia in patients with DM1. In this study, we optimised a PMO sequence to correct Clcn1 alternative splicing and successfully remedied the myotonic phenotype of a DM1 mouse model, the HSALR mouse. To enhance the efficiency of delivery of PMO into HSA ...[more]

PMID: 23873129

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Project description:RationaleMyotonic dystrophy type 1 (DM1) is an autosomal-dominant disorder associated with a short life expectancy and various symptoms, including grip myotonia. Even though grip myotonia decreases quality of life, activities of daily living (ADLs), and work performance, very few interventions provide symptomatic relief.Patient concernsIn this case report, we present a patient with DM1 and gradually worsening grip myotonia. A 35-year-old woman developed grip myotonia at age 27. She had no underlying diseases or family history of relevant conditions, including DM1. She was unresponsive to medication for several years.DiagnosisHer symptoms gradually worsened, and she was finally diagnosed with DM1 via genetic, neurologic, and laboratory testing in a tertiary hospital at age 32. She tried several medication therapies; however, she stopped medication at age 34 due a perceived poor response and several adverse events.InterventionAt the age of 35, she underwent 29 sessions (10 minutes per session) of electroacupuncture therapy on TE9 acupuncture point with 120 Hz electrical stimulation over 3 months.OutcomesAfter 3 months, relaxation time after maximal voluntary isometric contraction decreased from 59 to 2 seconds with treatment. Her Michigan Hand Outcomes Questionnaire score improved (total score, 66.6-75.9; ADL sub-score, 59.7-73.6; function sub-score, 70-90; satisfaction sub-score, 75-91.7). Her Measure Yourself Medical Outcome Profile 2 score also improved from 4.33 to 2. There were no serious adverse events.LessonsElectroacupuncture is a potential treatment modality and produced an immediate antimyotonic effect, and cumulative long-term treatment effect, in a patient with DM1 and grip myotonia. Other notable treatment outcomes included improving relaxation time, hand function, ADLs, and overall satisfaction. Electroacupuncture is a potential treatment modality for patients with DM1 and grip myotonia. Further prospective clinical studies are warranted to confirm this hypothesis.

Dataset Information

Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.

Publications

Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.

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