Arginase I mRNA therapy - a novel approach to rescue arginase 1 enzyme deficiency
| Autor: | Romesh R. Subramanian, Kirtika H. Asrani, Christopher J. Cheng, Lei Cheng |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Arginine Urea cycle disorder Diet therapy Hyperargininemia Biology complex mixtures 03 medical and health sciences Mice 0302 clinical medicine Pharmacotherapy In vivo Internal medicine medicine Animals Humans Urea RNA Messenger ARG1 Molecular Biology Arginase Cell Biology Hep G2 Cells medicine.disease Biological Therapy Mice Inbred C57BL 030104 developmental biology Endocrinology Mutation 030217 neurology & neurosurgery HeLa Cells Research Paper |
| Zdroj: | RNA biology. 15(7) |
| ISSN: | 1555-8584 |
| Popis: | Arginase I (ARG1) deficiency is an autosomal recessive urea cycle disorder, caused by deficiency of the enzyme Arginase I, resulting in accumulation of arginine in blood. Current Standard of Care (SOC) for ARG1 deficiency in patients or those having detrimental mutations of ARG1 gene is diet control. Despite diet and drug therapy with nitrogen scavengers, ~25% of patients suffer from severe mental deficits and loss of ambulation. 75% of patients whose symptoms can be managed through diet therapy continue to suffer neuro-cognitive deficits. In our research, we demonstrate in vitro and in vivo that administration of ARG1 mRNA increased ARG1 protein expression and specific activity in relevant cell types, including ARG1-deficient patient cell lines, as well as in wild type mice for up to 4 days. These studies demonstrate that ARG1 mRNA treatment led to increased functional protein expression of ARG1 and subsequently an increase in urea. Hence, ARG1 mRNA therapy could be a potential treatment option to develop for patients. |
| Databáze: | OpenAIRE |
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