Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy
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| Format: | Recurso digital |
| Language: | English |
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2018
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| author | Araújo-Vilar, David Domingo-Jiménez, Rosario Ruibal, Álvaro Aguiar, Pablo Ibáñez-Micó, Salvador Garrido Pumar, Miguel Martínez Olmos, Miguel Ángel López-Soler, Concepción Guillín-Amarelle, Cristina González Rodríguez, María Rodríguez Núñez, Antonio Álvarez Escudero, Julián Liñares Paz, Mercedes González Méndez, Blanca Rodríguez-García, Silvia Sánchez-Iglesias, Sofía |
| author_facet | Araújo-Vilar, David Domingo-Jiménez, Rosario Ruibal, Álvaro Aguiar, Pablo Ibáñez-Micó, Salvador Garrido Pumar, Miguel Martínez Olmos, Miguel Ángel López-Soler, Concepción Guillín-Amarelle, Cristina González Rodríguez, María Rodríguez Núñez, Antonio Álvarez Escudero, Julián Liñares Paz, Mercedes González Méndez, Blanca Rodríguez-García, Silvia Sánchez-Iglesias, Sofía |
| contents | <p><span>Celia’s encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.</span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_1038_s41431-017-0052-8 |
| institution | Zenodo |
| language | eng |
| publishDate | 2018 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy Araújo-Vilar, David Domingo-Jiménez, Rosario Ruibal, Álvaro Aguiar, Pablo Ibáñez-Micó, Salvador Garrido Pumar, Miguel Martínez Olmos, Miguel Ángel López-Soler, Concepción Guillín-Amarelle, Cristina González Rodríguez, María Rodríguez Núñez, Antonio Álvarez Escudero, Julián Liñares Paz, Mercedes González Méndez, Blanca Rodríguez-García, Silvia Sánchez-Iglesias, Sofía <p><span>Celia’s encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.</span></p> |
| title | Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy |
| url | https://doi.org/10.1038/s41431-017-0052-8 |