{"id":2074,"date":"2019-10-01T15:29:34","date_gmt":"2019-10-01T13:29:34","guid":{"rendered":"https:\/\/idibell.cat\/?page_id=2074"},"modified":"2024-12-17T15:11:27","modified_gmt":"2024-12-17T14:11:27","slug":"neurometabolic-diseases","status":"publish","type":"page","link":"https:\/\/idibell.cat\/en\/research\/neuroscience-area\/neuroscience-program\/neurometabolic-diseases\/","title":{"rendered":"Neurometabolic diseases"},"content":{"rendered":"\n

\n\t\tNeurometabolic diseases\n\t<\/h1>\n

\n\t\tSummary\n\t<\/h3>\n\t

Our mission is to improve disease management of rare brain disorders through precision medicine. This spans the whole spectrum from genomic diagnosis to disease-modifying treatments. A first research line revolves around adrenoleukodystrophy (ALD), made popular by the movie “Lorenzo’s Oil”. We are integrating multiomic approaches to gain insights into pathomechanisms and for drug target identification. These involve redox and metabolic homeostasis, mitochondria dynamics, proteostasis and cellular stress responses. Tailored preclinical tests have yielded four licensed patents, three phase II\/III clinical trials, and two Orphan Drug Designations. A second research line applies clinical and functional genomics for genomic diagnostics and novel gene discovery for brain white matter disorders. Through massive sequencing (WES and WGS), we are identifying novel disease-causing genes and modeling disease using iPS-derived brain organoid cultures and zebrafish. Results are advancing scientific knowledge while serving the undiagnosed patient’s community.<\/p>\n

300<\/h2>\n

Publications<\/h2>\n\t\t\t\t\"pnns_at_primary_somatosensory_cortex_in_mouse_brain_03\"\n\t\t\t\t\tStrategic lines<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\tGenomic Medicine for brain white matter diseases. From genomics diagnosis to novel gene and syndrome discovery.
\nMultiomics integration for therapeutic target and biomarker identification. Preclinical and clinical trials for adrenoleukodystrophy.\n

Microbiome as disease modifying agent in adrenoleukodystrophy<\/p>\n

Use of genomics for personalized medicine of Covid, patient stratification and therapeutic.<\/p>\n\t\t\t\t\tSelected Publications<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\t

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.<\/a><\/p>\n

Mohren L, Erdlenbruch F, Leit\u00e3o E, Kilpert F, H\u00f6nes GS, Kaya S, Schr\u00f6der C, Thieme A, Sturm M, Park J, Schl\u00fcter A, Ruiz M, Morales de la Prida M, Casasnovas C, Becker K, Roggenbuck U, Pechlivanis S, Kaiser FJ, Synofzik M, Wirth T, Anheim M, Haack TB, Lockhart PJ, J\u00f6ckel KH, Pujol A, Klebe S, Timmann D, Depienne C.Nat Commun. 2024 Sep 3;15(1):7665. doi: 10.1038\/s41467-024-52148-1.PMID:\u00a039227614<\/p>\n

Imbalanced mitochondrial dynamics contributes to the pathogenesis of X-linked adrenoleukodystrophy.<\/a><\/p>\n

Launay N, Lopez-Erauskin J, Bianchi P, Guha S, Parameswaran J, Coppa A, Torreni L, Schl\u00fcter A, Fourcade S, Paredes-Fuentes AJ, Artuch R, Casasnovas C, Ruiz M, Pujol A.Brain. 2024 Jun 3;147(6):2069-2084. doi: 10.1093\/brain\/awae038.PMID:\u00a038763511<\/p>\n

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.<\/a><\/p>\n

Schl\u00fcter A, V\u00e9lez-Santamar\u00eda V, Verdura E, Rodr\u00edguez-Palmero A, Ruiz M, Fourcade S, Planas-Serra L, Launay N, Guilera C, Mart\u00ednez JJ, Homedes-Pedret C, Albert\u00ed-Aguil\u00f3 MA, Zulaika M, Mart\u00ed I, Troncoso M, Tom\u00e1s-Vila M, Bullich G, Garc\u00eda-P\u00e9rez MA, Sobrido-G\u00f3mez MJ, L\u00f3pez-Laso E, Fons C, Del Toro M, Macaya A; HSP\/ataxia workgroup; Beltran S, Guti\u00e9rrez-Solana LG, P\u00e9rez-Jurado LA, Aguilera-Albesa S, de Munain AL, Casasnovas C, Pujol A.Genome Med. 2023 Sep 7;15(1):68. doi: 10.1186\/s13073-023-01214-2.PMID:\u00a037679823<\/p>\n

Biomarker-based risk prediction for the onset of neuroinflammation in X-linked adrenoleukodystrophy.<\/a><\/p>\n

Weinhofer I, Rommer P, Gleiss A, Ponleitner M, Zierfuss B, Waidhofer-S\u00f6llner P, Fourcade S, Grabmeier-Pfistershammer K, Reinert MC, G\u00f6pfert J, Heine A, Yska HAF, Casasnovas C, Cantar\u00edn V, Bergner CG, Mallack E, Forss-Petter S, Aubourg P, Bley A, Engelen M, Eichler F, Lund TC, Pujol A, K\u00f6hler W, K\u00fchl JS, Berger J.EBioMedicine. 2023 Oct;96:104781. doi: 10.1016\/j.ebiom.2023.104781. Epub 2023 Sep 7.PMID:\u00a037683329<\/p>\n

RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.<\/a><\/p>\n

Launay N, Ruiz M, Planas-Serra L, Verdura E, Rodr\u00edguez-Palmero A, Schl\u00fcter A, Goicoechea L, Guilera C, Casas J, Campelo F, Jouanguy E, Casanova JL, Boespflug-Tanguy O, Vazquez Cancela M, Guti\u00e9rrez-Solana LG, Casasnovas C, Area-Gomez E, Pujol A.J Clin Invest. 2023 Jul 17;133(14):e162836. doi: 10.1172\/JCI162836.PMID:\u00a037463447<\/p>\n

Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity.<\/a><\/p>\n

Planas-Serra L, Launay N, Goicoechea L, Heron B, Jou C, Juli\u00e1-Palacios N, Ruiz M, Fourcade S, Casasnovas C, De La Torre C, Gelot A, Marsal M, Loza-Alvarez P, Garc\u00eda-Cazorla \u00c0, Fatemi A, Ferrer I, Portero-Otin M, Area-G\u00f3mez E, Pujol A.J Clin Invest. 2023 May 15;133(10):e162957. doi: 10.1172\/JCI162957.PMID: 36951944<\/p>\n

Loss of seryl-tRNA synthetase (SARS1<\/em>) causes complex spastic paraplegia and cellular senescence.<\/a><\/p>\n

Verdura E, Senger B, Raspall-Chaure M, Schl\u00fcter A, Launay N, Ruiz M, Casasnovas C, Rodriguez-Palmero A, Macaya A, Becker HD, Pujol A.J Med Genet. 2022 Dec;59(12):1227-1233. doi: 10.1136\/jmg-2022-108529. Epub 2022 Aug 30.PMID:\u00a036041817<\/p>\n

Activating cannabinoid receptor 2 preserves axonal health through GSK-3\u03b2\/NRF2 axis in adrenoleukodystrophy.<\/a><\/p>\n

Parameswaran J, Goicoechea L, Planas-Serra L, Pastor A, Ruiz M, Calingasan NY, Guilera C, Aso E, Boada J, Pamplona R, Portero-Ot\u00edn M, de la Torre R, Ferrer I, Casasnovas C, Pujol A, Fourcade S.Acta Neuropathol. 2022 Aug;144(2):241-258. doi: 10.1007\/s00401-022-02451-2. Epub 2022 Jul 1.PMID:\u00a035778568<\/p>\n

Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study.<\/a><\/p>\n

Davalos V, Garc\u00eda-Prieto CA, Ferrer G, Aguilera-Albesa S, Valencia-Ramos J, Rodr\u00edguez-Palmero A, Ruiz M, Planas-Serra L, Jordan I, Alegr\u00eda I, Flores-P\u00e9rez P, Cantar\u00edn V, Fumad\u00f3 V, Viadero MT, Rodrigo C, M\u00e9ndez-Hern\u00e1ndez M, L\u00f3pez-Granados E, Colobran R, Rivi\u00e8re JG, Soler-Palac\u00edn P, Pujol A, Esteller M.EClinicalMedicine. 2022 Jun 25;50:101515. doi: 10.1016\/j.eclinm.2022.101515. eCollection 2022 Aug.PMID:\u00a035770252<\/p>\n

Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy.<\/a><\/p>\n

Guasto A, Dubail J, Aguilera-Albesa S, Paganini C, Vanhulle C, Haouari W, Gorr\u00eda-Redondo N, Aznal-Sainz E, Boddaert N, Planas-Serra L, Schl\u00fcter A, V\u00e9lez-Santamar\u00eda V, Verdura E, Bruneel A, Rossi A, Huber C, Pujol A, Cormier-Daire V.Brain. 2022 Oct 21;145(10):3711-3722. doi: 10.1093\/brain\/awac110.PMID:\u00a035325049<\/p>\n

 <\/p>\n\t\t\t\t\tSelected Projects<\/a>\n\t\t\t\t\t\t\t\t\t\t\tExpand<\/i><\/a>\n\t\t\t\t\t