LABORATORIO DE ENFERMEDADES DEMIELINIZANTES Y TERAPIA GÉNICA

La mielina es un componente vital del sistema nervioso, es esencial para la transmisión del impulso nervioso y protege la integridad de las neuronas y sus axones. En las enfermedades demielinizantes como la Esclerosis Múltiple están afectadas la mielina y las células que sintetizan mielina (oligodendrocitos). Asimismo, la pérdida de mielina está estrechamente asociada a enfermedades neurodegenerativas como el Alzheimer y la Esclerosis Lateral Amiotrófica. Aunque el sistema nervioso central puede generar nuevos oligodendrocitos capaces de remielinizar, la eficacia de esta regeneración es limitada, y la remielinización incompleta deviene en la pérdida progresiva de funciones neurológicas. Las terapias actuales para estas enfermedades son incapaces de recuperar y/o frenar el decline crónico de las funciones neurológicas en los pacientes. En nuestro laboratorio estamos interesados en el desarrollo de terapias regenerativas para modular la expresión de genes capaces de promover la producción endógena de oligodendrocitos y la remielinización. En particular, mediante el uso de análogos artificiales de microARNs administrados con vectores virales (virus asociados a adenovirus) y no virales (vesículas extracelulares). El desarrollo de terapias regenerativas es imprescindible en el avance de la lucha contra enfermedades del sistema nervioso que presentan demielinización crónica tal como la Esclerosis Múltiple.
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OBJETIVOS DE NUESTRO LABORATORIO:

Estudio de las capacidades terapéuticas de análogos artificiales de microARNs para promover la regeneración de mielina:

  • Determinar la especificidad y el efecto terapéutico de análogos artificiales de microARNs administrados por medio de vesículas extracelulares y de virus asociados a adenovirus.
  • Evaluar el efecto terapéutico de análogos artificiales de microARNs para promover la remielinización en modelos experimentales in vivo de Esclerosis Múltiple y otras patologías con demielinización crónica.
ENGLISH VERSION
Demyelinating Diseases and Gene Therapy Laboratory

 

Myelin is a vital component of the central nervous system (CNS), is essential for the propagation of nerve impulses and protects the integrity of neurons and their axons. Myelin and myelin-producing cells (oligodendrocytes) are affected in demyelinating diseases such as multiple sclerosis. Myelin loss is also associated with neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis. The CNS has the potential to generate new oligodendrocytes capable of remyelinate demyelinating lesions. However, myelin regeneration is limited and incomplete remyelination is in part responsible for the progressive loss of neurological functions. Current therapies for these diseases are unable to recover and / or slow the chronic decline of neurological functions in patients. In our laboratory we are interested in the development of regenerative therapies that modulate the expression of genes capable of promoting the endogenous production of oligodendrocytes and remyelination. Particularly, using microRNAs mimics administered by viral (adenovirus-associated virus) and non-viral vectors (extracellular vesicles). The development of regenerative therapies is essential in the fight against diseases of the CNS and particularly in chronic demyelinating diseases such as multiple sclerosis.

 

Current projects:

Therapeutic use of microRNAs mimics to promote myelin regeneration:

1- To determine the specificity and therapeutic effects of microRNAs mimics administered by adenovirus associated viruses and extracellular vesicles.

2- To evaluate the therapeutic effects of microRNAs mimics to promote remyelination in experimental models of multiple sclerosis and other pathologies with chronic demyelination.

PUBLICACIONES/PUBLICATIONS

MIR-219 COOPERATES WITH MIR-338 IN MYELINATION AND PROMOTES MYELIN REPAIR IN THE CNS
Wang H, Moyano AL, Ma Z, Deng Y, Zhang L, Lin Y, Zhao C, Zhang L, Jiang M, He X, Ma Z, Lu F, Xin M, Zhou W, Yoon SO, Bongarzone ER and Lu QR. (2017) “miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS”. Dev Cell. Mar 27;40(6):566-582.
SULFATIDES IN EXTRACELLULAR VESICLES ISOLATED FROM PLASMA OF MULTIPLE SCLEROSIS PATIENTS
Moyano AL, Li G, Boullerne AI, Feinstein DL, Hartman E, Skias D, Balavanov R, van Breemen R, Bongarzone ER, Månsson J-E and Givogri MI. (2016) “Sulfatides in extracellular vesicles isolated from plasma of Multiple Sclerosis patients”. J Neurosci Res. Dec, 94(12):1579-1587.
LEVELS OF PLASMA SULFATIDES C18:0 AND C24:1 CORRELATE WITH DISEASE STATUS IN RELAPSING-REMITTING MULTIPLE SCLEROSIS
Moyano AL, Pituch K, Li G, van Breemen R, Mansson JE and Givogri MI. (2013) “Levels of plasma sulfatides C18:0 and C24:1 correlate with disease status in relapsing-remitting Multiple Sclerosis”. J Neurochem, 125 (5): 600-4.
NOVEL ANTIBODIES REACTING WITH TWO NEIGHBORING GANGLIOSIDES ARE INDUCED IN RABBITS IMMUNIZED WITH BOVINE BRAIN GANGLIOSIDES
Moyano AL, Comín R, Vilcaes AA, Funes SC, Roth GA, Irazoqui FJ and Nores GA. (2012) “Novel antibodies reacting with two neighboring gangliosides are induced in rabbits immunized with bovine brain gangliosides”. Glycobiology, 22 (12): 1768-74.
VALIDATION OF A RABBIT MODEL OF NEUROPATHY INDUCED BY IMMUNIZATION WITH GANGLIOSIDE
Moyano AL, Comín R, Lardone RD, Alaniz ME, Theaux R, Irazoqui FJ and Nores GA. (2008) “Validation of a rabbit model of neuropathy induced by immunization with ganglioside”. J Neurol Sci, 272 (1‐2): 110‐

MIEMBROS DEL LABORATORIO/LABORATORY MEMBERS

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Principal Investigator IUCBC