Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy.
David Araújo-VilarRosario Domingo-JiménezÁlvaro RuibalPablo AguiarSalvador Ibáñez-MicóMiguel Garrido-PumarMiguel Ángel Martínez-OlmosConcepción López-SolerCristina Guillín-AmarelleMaría González-RodríguezAntonio Rodríguez-NúñezJulián Álvarez-EscuderoMercedes Liñares-PazBlanca González-MéndezSilvia Rodríguez-GarcíaSofía Sánchez-IglesiasPublished in: European journal of human genetics : EJHG (2018)
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.
Keyphrases
- randomized controlled trial
- computed tomography
- fatty acid
- poor prognosis
- early onset
- mental health
- case report
- type diabetes
- magnetic resonance imaging
- dna methylation
- positron emission tomography
- physical activity
- cell death
- autism spectrum disorder
- small molecule
- gene expression
- young adults
- cerebral ischemia
- skeletal muscle
- metabolic syndrome
- cell cycle arrest
- brain injury
- single cell
- long non coding rna
- intellectual disability
- pet imaging
- early life
- combination therapy
- replacement therapy
- case control