Dataset Information

Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome.

ABSTRACT:

Objective

We generated an adeno-associated virus (AAV) vector in which the human SLC2A1 gene was expressed under the synapsin I promoter (AAV-hSLC2A1) and examined if AAV-hSLC2A1 administration can lead to functional improvement in GLUT1-deficient mice.

Methods

AAV-hSLC2A1 was injected into heterozygous knock-out murine Glut1 (GLUT1^+/-) mice intraperitoneally (systemic; 1.85 × 10¹¹ vg/mouse) or intra-cerebroventricularly (local; 1.85 × 10¹⁰ vg/mouse). We analyzed GLUT1 mRNA and protein expression, motor function using rota-rod and footprint tests, and blood and cerebrospinal fluid (CSF) glucose levels.

Results

Vector-derived RNA was detected in the cerebrum for both injection routes. In the intra-cerebroventricular injection group, exogenous GLUT1 protein was strongly expressed in the cerebral cortex and hippocampus near the injection site. In the intraperitoneal injection group, exogenous GLUT1 protein was mildly expressed in neural cells throughout the entire central nervous system. The motor function test and CSF/blood glucose ratio were significantly improved following intra-cerebroventricular injection.

Conclusions

AAV-hSLC2A1 administration produced exogenous GLUT1 in neural cells and improved CSF glucose levels and motor function of heterozygous knock-out murine Glut1 mice.

SUBMITTER: Nakamura S

PROVIDER: S-EPMC5238605 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome.

Nakamura Sachie S Osaka Hitoshi H Muramatsu Shin-Ichi SI Takino Naomi N Ito Mika M Aoki Shiho S Jimbo Eriko F EF Shimazaki Kuniko K Onaka Tatsushi T Ohtsuki Sumio S Terasaki Tetsuya T Yamagata Takanori T

Molecular genetics and metabolism reports 20170115

<h4>Objective</h4>We generated an adeno-associated virus (AAV) vector in which the human <i>SLC2A1</i> gene was expressed under the synapsin I promoter (AAV-h<i>SLC2A1</i>) and examined if AAV-h<i>SLC2A1</i> administration can lead to functional improvement in <i>GLUT1</i>-deficient mice.<h4>Methods</h4>AAV-h<i>SLC2A1</i> was injected into heterozygous knock-out murine <i>Glut1</i> (GLUT1<sup>+/-</sup>) mice intraperitoneally (systemic; 1.85 × 10<sup>11</sup> vg/mouse) or intra-cerebroventricula ...[more]

PMID: 28119822

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Project description:BackgroundGlucose transporter 1 deficiency syndrome (Glut1DS) was initially reported by De Vivo and colleagues in 1991. This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum. It is a treatable neuro-metabolic condition, where prompt diagnosis and initiation of ketogenic dietary therapy can markedly enhance the prognosis. However, due to its rarity, Glut1DS is susceptible to misdiagnosis or missed diagnosis, which can lead to delayed treatment and irreversible dysfunction of the central nervous system. To promote diagnostic awareness and effective treatments, the recommendations for diagnosis and treatment have been developed.MethodsThe panel on Glut1DS included 28 participants from the members of the Ketogenic Diet Professional Committee of the Chinese Epilepsy Association and Chinese experts with extensive experience in managing Glut1DS. All authors extensively reviewed the literature, and the survey results were discussed in detail over several online meetings. Following multiple deliberative sessions, all participants approved the final manuscript for submission.ResultsEarly diagnosis and timely treatment of Glut1DS are crucial for improving prognosis. Physicians should be alert to suspiction of this disease if the following clinical manifestations appear: seizures, episodic or persistent movement disorders (often triggered by fasting, fatigue, or exercise), delayed motor and cognitive development. Characteristic clinical presentations may include seizures combined with movement disorders, episodic eye-head movements, and paroxysmal exercise-induced dyskinesia (PED). In these cases, genetic testing should be promptly completed, and a lumbar puncture should be performed if necessary. The ketogenic diet is internationally recognized as the first-line treatment; the earlier it is started, the better the prognosis. It can effectively control seizures and improve motor disorders. Antiepileptic drug treatment is generally ineffective or provides limited symptom improvement before starting the ketogenic diet.ConclusionThe recommendations provide clinicians with a relatively systematic guide for the rapid identification, diagnosis, and timely treatment of Glut1DS.

Dataset Information

Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome.

Objective

Methods

Results

Conclusions

Publications

Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome.

Similar Datasets

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