Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy.

Abstract

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.

• Authors: David Araújo-Vilar, Rosario Domingo-Jiménez, Álvaro Ruibal, Pablo Aguiar, Salvador Ibáñez-Micó, Miguel Garrido-Pumar, Miguel Ángel Martínez-Olmos, Concepción López-Soler, Cristina Guillín-Amarelle, María González-Rodríguez, Antonio Rodríguez-Núñez, Julián Álvarez-Escudero, Mercedes Liñares-Paz, Blanca González-Méndez, Silvia Rodríguez-García, Sofía Sánchez-Iglesias
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 26 Issue 3 Pg. 396-406 (03 2018) ISSN: 1476-5438 [Electronic] England
• PMID: 29367704 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BSCL2 protein, human
• Fatty Acids, Unsaturated
• GTP-Binding Protein gamma Subunits
• Leptin
• metreleptin

Topics

• Brain Diseases (diet therapy, drug therapy, genetics)
• Cell Line, Tumor
• Child
• Diet
• Fatty Acids, Unsaturated (administration & dosage, therapeutic use)
• Female
• GTP-Binding Protein gamma Subunits (genetics, metabolism)
• Humans
• Leptin (administration & dosage, analogs & derivatives, therapeutic use)
• Lipodystrophy (diet therapy, drug therapy, genetics)
• Syndrome