Vectors, Gene and Cell Therapy

Luís Almeida

PhD, Group Leader

The Group of Gene and Stem Cell Therapy of Brain Disorders is devoted to the creation of new effective therapies for brain diseases that can be moved from the bench to the bedside. For this, the group designs and uses technological platforms based on viral and non-viral gene transfer vectors, and induced pluripotent stem cells for the:

  1. Establishment of models of brain disease;
  2. Study of disease mechanisms;
  3. Development of new molecular and stem cell, therapeutic and prophylactic approaches for brain disorders, particularly neurodegenerative diseases, notably Machado-Joseph's disease (MJD)/ spinocerebellar ataxia type 3, as well as brain tumours.

The group results from a restructuration of the former “Vectors and Gene Therapy” group, and has a strong expertise in gene transfer (viral and non-viral) and stem cells for brain disease-modeling and therapy. Our technological platforms include:

  • Lentiviral and adeno-associated AAV viral vectors;
  • Exosomes and nanoparticles targeted to the brain repair and vaccination;
  • Gene editing with CRISPR-Cas9;
  • Induced pluripotent stem cells for disease modelling;
  • Neural Stem Cell and mesenchymal stromal cells transplantation for brain repair;
  • Biomarker discovery from patient fluids.

The research developed relies on collaborative efforts of a dynamic team including fundamental, pre-clinical, and clinical, junior and senior researchers in a total of 17 PhD-holding integrated members of which 4 faculty and a total of 32 members. The team develops nationally funded projects, including a national research infrastructure for generation and use of viral vectors for gene transfer – ViraVector, as well as three international projects, including the project ESMI-to identify disease biomarkers and prepare a trial ready cohort of MJD patients, and the leadership of two JPND consortia: Synspread-for cross disease mechanistic investigation and ModelPolyQ- for generation of improved models of Polyglutamine diseases.

Group Members

Group Members

Group members are: Luis Pereira Almeida (PhD, Group Leader), Alana Duarte, Ana Catarina Brás (MD), Ana Cristina Ferreira, Ana Maria Cardoso (PhD), Ana Patrícia Marques (PhD), Ana Teresa Simões (PhD), Beatriz Mestre, Carlos Mato (PhD), Catarina Miranda (PhD), Catarina Morais, David Ramos, Dina Pereira, Edna Soares, Elsa Henriques (PhD), Inês Cunha (MD), Joana Ribeiro (MD), João Costa, Liliana Mendonça (PhD), Luisa Cortes (PhD), Magda Santana (PhD), Maria Amália Jurado (PhD), Maria da Conceição Pedroso de Lima (PhD), Maria Inês Martins, Miguel Lopes, Olga Borges Ribeiro (PhD), Patrícia Albuquerque, Rita Perfeito (PhD), Rui Nobre (PhD), Sandra Jesus (PhD), Sara Lopes, Sérgio Sousa (MD, PhD), Sónia Duarte (PhD), Susana Conceição, Tânia Marante, Vitor Carmona (PhD).

Selected Publications

Santana, Magda M.; Paixão, Susana; Cunha-Santos, Janete; Silva, Teresa Pereira; Trevino-Garcia, Allyson; Gaspar, Laetitia S.; Nóbrega, Clévio; et al. "Trehalose alleviates the phenotype of Machado–Joseph disease mouse models". Journal of Translational Medicine 18 1 (2020). doi: 10.1186/s12967-020-02302-2.

Lopes, Sara Monteiro; Faro, Rosário; Lopes, Miguel Monteiro; Onofre, Isabel; Mendonça, Nuno; Ribeiro, Joana; Januário, Cristina; Nobre, Rui Jorge; Pereira de Almeida, Luís. "Protocol for the Characterization of the CAG Tract and Flanking Polymorphisms in Machado-Joseph Disease: Impact on Diagnosis and Development of Gene-Based Therapies". The Journal of Molecular Diagnostics (2020). doi: 10.1016/j.jmoldx.2020.03.003.

Ana C Silva, Diana D Lobo, Inês M Martins, Sara M Lopes, Carina Henriques, Sónia P Duarte, Jean-Cosme Dodart, Rui Jorge Nobre, Luis Pereira de Almeida, Antisense oligonucleotide therapeutics in neurodegenerative diseases: the case of polyglutamine disorders, Brain, 2019. doi: 10.1093/brain/awz328.

Liliana S. Mendonça, Clévio Nóbrega, Silvia Tavino, Maximilian Brinkhaus, Carlos Matos, Sandra Tomé, Daniel Henriques, Brian K. Kaspar, and Luís Pereira de Almeida. Ibuprofen enhances synaptic function and neural progenitors proliferation markers and improves neuropathology and motor coordination in Machado-Joseph disease models. Human Molecular Genetics. 2019. doi: 10.1093/hmg/ddz097.

Clévio Nóbrega, Liliana Mendonça, Adriana Marcelo, Antonin Lamaziere, Sandra Tomé, Gaetan Despres, Carlos A. Matos, Fatich Mechmet, Dominique Langui, Wilfred den Dunnen, Luis Pereira de Almeida*, Nathalie Cartier* and Sandro Alves*; Restoring brain cholesterol turnover improves autophagy and has therapeutic potential in mouse models of spinocerebellar ataxia. Acta Neuropathologica. 2019. doi: 10.1007/s00401-019-02019-7.

Marcelo, A.; Brito, F.; Carmo-Silva, S.; Matos, C.A.; Alves-Cruzeiro, J.; Vasconcelos-Ferreira, A.; Koppenol, R.; et al. "Cordycepin activates autophagy through AMPK phosphorylation to reduce abnormalities in Machado-Joseph disease models". Human molecular genetics 28 1 (2019): 51-63. doi: 10.1093/hmg/ddy328.

Walter, Jonas; Bolognin, Silvia; Antony, Paul M.A.; Nickels, Sarah L.; Poovathingal, Suresh K.; Salamanca, Luis; Magni, Stefano; et al. "Neural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality". Stem Cell Reports 12 5 (2019): 878-889. doi: 10.1016/j.stemcr.2019.03.004.

Miranda C, Marcelo A, Silva T, Barata J, Vasconcelos-Ferreira A, Pereira D, Nóbrega C, Duarte S, Barros I, Alves J, Sereno J, Petrella L, Castelhano J, Paiva VH, Rodrigues-Santos P, Alves V, Nunes-Correia I, Nobre R, Gomes C, Castelo-Branco M, Pereira de Almeida L. Repeated Mesenchymal Stromal Cells Treatment Sustainably Alleviate Machado-Joseph Disease. Molecular Therapy. 2018. doi: 10.1016/j.ymthe.2018.07.007.

Gonçalves, N.; Simões, A.T.; Prediger, R.D.; Hirai, H.; Cunha, R.A.; Pereira de Almeida, L.. "Caffeine alleviates progressive motor deficits in a transgenic mouse model of spinocerebellar ataxia". Annals of Neurology 81 3 (2017): 407-418. doi: 10.1002/ana.24867.

Carmona V, Cunha-Santos J, Onofre I, Simões AT, Vijayakumar U, Davidson BL and Pereira de Almeida L. Unravelling endogenous MicroRNAs system dysfunction as a new pathophysiological mechanism in Machado-Joseph disease. Molecular Therapy. 2017 doi: 10.1016/j.ymthe.2017.01.021.

Janete Cunha-Santos, Joana Duarte-Neves, Vitor Carmona, Leonard Guarente, Luís Pereira de Almeida* & Cláudia Cavadas* Caloric Restriction blocks neuropathology and motor deficits in Machado-Joseph Disease mouse models through activation of the SIRT1 pathway. Nature Communications. 2016 doi: 10.1038/ncomms11445.

Saraiva, J.; Nobre, R.J.; Pereira de Almeida, L.. "Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9". Journal of Controlled Release 241 (2016): 94-109. doi: 10.1016/j.jconrel.2016.09.011.

Conceição M, Mendonça L, Nóbrega C, Gomes C, Costa P, Hirai H, Moreira JN, Lima MC, Manjunath N, Pereira de Almeida L. Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype. Biomaterials. 2016 doi: 10.1016/j.biomaterials.2015.12.021.

Dubinsky AN, Dastidar SG, Hsu CL, Zahra R, Djakovic SN, Duarte S, Esau CC, Spencer B, Ashe TD, Fischer KM, MacKenna DA, Sopher BL, Masliah E, Gaasterland T, Chau BN, Pereira de Almeida L, Morrison BE, La Spada AR. Let-7 Coordinately Suppresses Components of the Amino Acid Sensing Pathway to Repress mTORC1 and Induce Autophagy. Cell Metabolism. 2014 doi: 0.1016/j.cmet.2014.09.001.

Selected Projects

SCA-CYP - Gene Therapy for Cerebellar Ataxias: restoring cholesterol metabolism by targeting brain cholesterol 24 hydroxylase (CYP46A1). E-RARE consortium. PI: Luís Pereira de Almeida.

Advanced models of polyglutamine disorders (HD, SCA3, SCA7); Joint Programme on Neurodegenerative Disease Research - JPND. Consortium Coordinator: Luís Pereira de Almeida.

SpreadSilencing - Neurodegeneration blocking by genetic silencers dispersion. FCT - Fundação para a Ciência e Tecnologia. PI: Luís Pereira de Almeida.

The impact of induced pluripotent stem cells-derived neuroepithelial stem cells transplantation in Machado-Joseph disease. FCT - Fundação para a Ciência e Tecnologia. PI: Liliana Mendonça.

Role of microRNA deregulation in Machado-Joseph Disease: On the development of a microRNA-based therapeutic strategy. FCT - Fundação para a Ciência e Tecnologia. PI: Sónia Duarte.

BrainHealth 2020. CENTRO2020 (2017-2020). PI: Luís Pereira de Almeida.

ViraVector, National Infrastructure for production and research with viral vectors. CENTRO2020. PI: Luís Pereira de Almeida.

Go to top