RT Journal Article
T1 Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy
A1 Araujo-Vilar, David
A1 Domingo-Jiménez, Rosario
A1 Ruibal, Álvaro
A1 Aguiar, Pablo
A1 Ibáñez-Micó, Salvador
A1 Garrido Pumar, Miguel
A1 Martínez Olmos, Miguel Ángel
A1 López-Soler, Conecepción
A1 Guillín-Amarelle, Cristina
A1 González Rodríguez, María
A1 Rodríguez Núñez, Antonio
A1 Álvarez Escudero, Julián
A1 Liñares Paz, Mercedes
A1 González Méndez, Blanca
A1 Rodríguez-García, Silvia
A1 Sánchez Iglesias, Sofía
AB 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.
PB Springer Nature
YR 2018
FD 2018
LK http://hdl.handle.net/10347/32481
UL http://hdl.handle.net/10347/32481
LA eng
NO Araújo-Vilar, D., Domingo-Jiménez, R., Ruibal, Á. et al. Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia’s encephalopathy. Eur J Hum Genet 26, 396–406 (2018)
NO This work was supported by the Fundación Mutua Madrileña and by the Instituto de Salud Carlos III and the European Regional Development Fund, FEDER (PI13/00314).
DS Minerva
RD 30 abr 2026