Mitochondrial Medicine

The Mitochondrial Medicine group lead by Dario Brunetti, carries out translational research aimed at:

1) understanding the molecular mechanisms that link mitochondrial dysfunctions (of genetic origin or related to aging) to neuromuscular degenerative processes and metabolic disorders.

2) development of new metabolic, pharmacological and gene therapy strategies for restoring the functionality of mitochondria.

The preclinical research activity is carried out using or creating (through gene editing) both in vitro models (patient fibroblasts, iPS, NPCs, Organoids) and in vivo models (genetically modified mice and pigs).

The laboratory is located at the U.O. of Medical Genetics and Neurogenetics of the IRCCS Foundation Neurological Institute "C. Besta" and it integrates with the diagnostic and clinical activities of the other groups ensuring fruitful multidisciplinary, translational and precision medicine research (from bed to bench and back).

Currently 3 macro research areas are active:

1) Study of the role of PITRM1 in neurodegenerative diseases. This research area includes three other sub-areas:

a) role of PITRM1 in the metabolism of beta amyloid and Alzheimer's disease.

b) role of PITRM1 in the dysregulated maturation of Frataxin and in spinocerebellar ataxia.

c) development of pharmacological and gene therapy approaches for the restoration of mitochondrial proteostasis.

2) Development of precision medicine approaches for Leigh's syndrome. This research area includes three other sub-areas:

a) development of metabolic therapies aimed at correcting neurodevelopmental defects in in vitro (2D and 3D) and in vivo (KO pigs) models deficient in the Surf1 gene.

b) Development of a fetal in utero gene therapy (IUFGT) on the Surf1KO pig model.

c) Identification through "drug repositioning" of effective drugs for Leigh's syndrome.

3) Pharmacological stimulation of mitochondrial biogenesis, dynamics and mitophagy for the prevention of neuromuscular degenerative processes related to aging.

Our lab is about 350 square meters and it is equipped with the principal instruments for molecular biology including an Automated DNA sequencers ABI3130XL for Sanger's sequencing, and a MiSeq system for NGS applications; biochemistry (electrophoresis, SDS-PAGE, 1D and 2D-BNE, spectrophotometer) tissue culture rooms fully equipped for iPS cell culture and facility for viral vectors manipulation, with several light microscopes including 1 confocal microscope and a facility for radioisotope-based experiments.

PI funded projects:

2020 FRRB early career award- COD 1740526: “Precision Medicine Applied to Leigh Syndrome at different stages: development of a Neonatal metabolic supplementation and a fetal gene THERapy approach” Budget: 557.800 €

2020 Telethon spring SEED grant n. GSP20003_PAsAtaxia002: “Dysregulated Frataxin processing in the pathogenesis of PITRM1-dependent Spinocerebellar Ataxia”. Budget: 47.500 €

2020 Commissioned Research by Societè des Produits Nestlè SA: “Induction of autophagy to prevent age related diseases”; Budget: 35.000 €

Partnership projects:

2020 Bando SEED Unimi – COD. 1050: “Mitochondria and Alzheimer’s disease: focus on beta-amyloid processing by PITRM1 and mitochondrial proteases-MItoAD”.

2020 European Joint Programme on Rare Diseases (EJP RD) H2020, grant n° EJPRD20-010: “A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome (MILS) “

Contact:

Dario Brunetti, PhD
Fondazione IRCCS Istituto Neurologico "C.Besta"
Via Temolo 4, 20126 Milano, Italy
Tel: +39 02-23942633
e-mail (1): dario.brunetti@istituto-besta.it
e-mail (2): dario.brunetti@unimi.it

@Mito_Therapy