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Accelerating the discovery of new drugs to treat spinal cord injuries using zebrafish

By Cristina Bastos On 23 July, 2019 2019 | iMM Corner Comments Off on Accelerating the discovery of new drugs to treat spinal cord injuries using zebrafish No tags

The new platform enables effective drug screening and selection

A research team led by Leonor Saúde, lead researcher at iMM and Invited Associate Professor at the Faculty of Medicine of the University of Lisbon, in partnership with the iMM-based company Technophage, SA, have devised a simple and effective platform that uses zebrafish to discover and identify new drugs to treat spinal cord injuries. This open-access report published this week on the scientific journal Scientific Reports*, is the proof-of-concept that, combined with drug repositioning strategies, it has the potential to accelerate the period from the discovery of new therapeutic targets to their clinical use.

Spinal cord injuries can have devastating consequences because of their importance in everyday activities such as walking, but also because of their inability to regenerate, leading to permanent disabilities. These injuries are a complex clinical condition for which current treatment options have limited success in neurological and/or functional recovery. “Due to the complex nature of spinal cord injuries, it is likely that for significant functional recovery different targeting therapies are needed,” says Leonor Saúde, adding, “with this work we have shown that by using zebrafish we can accelerate the discovery of new therapeutic targets for spinal cord injuries.”

“With this project we designed a simple and effective platform that allows to test a large number of molecules and select them based on their ability to accelerate zebrafish spinal cord regeneration. Our platform is a model of spinal cord transection in zebrafish larvae where we have tested different therapeutic protocols and evaluated their effectiveness through larval behaviour and its locomotor function over time”, explains Diana Chapela, PhD student and leading author of this project. The researchers first validated this platform by testing human spinal cord injury molecules that underwent clinical trials, such as Riluzole, Minocycline and D-Cycloserine. The results showed that these drugs can also accelerate spinal cord regeneration in zebrafish.

“We then tested on our zebrafish platform more than 100 FDA-approved molecules for other conditions and identified a molecule with motor recovery properties in zebrafish larvae, Tranexamic Acid,” says Leonor Saúde. The efficiency of this drug was then tested in the spinal cord injury model of a rodent. “Our results show that this molecule, which is a procoagulant agent, has the ability to improve motor function in spinal cord injured mammals,” the researcher adds.

These promising results show the significant potential of this platform, which “combined with drug repositioning strategies, has the ability to accelerate the rapid adaptation of new treatments for spinal cord injuries in humans.”

This project was developed in a partnership between Leonor Saúde’s laboratory and Technophage, SA, and was funded by Technophage, SA and the Foundation for Science and Technology.

* Diana Chapela, Sara Sousa, Isaura Martins, Ana Margarida Cristóvão, Patrícia Pinto, Sofia Corte-Real & Leonor Saúde (2019) A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals. Scientific Reports.

Leonor Saúde and Diana Chapela. Credits: Cláudia Silva, iMM.

5-day-old zebrafish larvae, in which motor neurons labelled with a green fluorescent protein can be seen. Credits: Diana Chapela, iMM.

5-day-old zebrafish larvae. Credits: Diana Chapela, iMM.

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Index – News # 92 | jul. 2019
 United for Science
 Meet the FMUL Degree in Nutrition Sciences
 Universidade de Macau em visita à Faculdade de Medicina
 CCUL a pioneer in cardiovascular research among the best National R & D Units
 FCT atribui classificação de Muito Bom ao ISAMB
 GAPIC, 30 years Supporting Science
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 Bibliotecas de Saúde da ULisboa, vencem Prémio de Melhor Póster no IX Encontro Ibérico EDICIC 2019 – Dados Abertos e Inclusão Digital na Era do Big Data
 Rui Tato Marinho – 30 years curing people with Hepatitis C
 ISAMB discusses the effects of environmental change on Human Health
 II Congresso Nacional de Comunicação Clínica em Cuidados de Saúde
 ClinMed 2019 Summer School – 2nd Edition at the Faculty of Medicine of the University of Lisbon!
 FMUL Nutrition Laboratory Summer School
 III Sessão NeuroSeS
 GAPIC Alumni Network – GAPIC, 30 years Connecting Researchers
 FMUL student participates in the NGOs Annual Consultations Meetings in the HC of the United Nations.
 GAPIC: The Student Perspective
 The steps and moments on the path of a GAPIC Alumni
 GAPIC David Ferreira Award GAPIC – 30 years Valuing Science
 “Education through Science” Programme – GAPIC, 30 years Promoting Science
 AstraZeneca Foundation/FMUL Research Grant GAPIC, 30 years Driving Science
 Celebrating 30 years of GAPIC
 Publicações Científicas (FMUL / HSM / IMM) junho – julho | 2019
 Blood vessel communication tools and how zebrafish can help find new drugs to treat spinal cord injuries
 Accelerating the discovery of new drugs to treat spinal cord injuries using zebrafish
 How to align communication skills
 Ana and the memories from the breath of dust
 Professor José David Ferreira – Biographical Note
 Medicina, Informação, Autonomia e Criticismo
 O Dia da nossa Faculdade – Save the Date
 Workshop Impacto das Alterações Climáticas na Saúde – NOV’19
 Save the Date – Homenagem ao Professor Fernando Lopes da Silva
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100 AnosPropriedade e Edição: Faculdade de Medicina da Universidade de Lisboa NIPC: 502662875  Periodicidade: Mensal  Diretor: Prof. Doutor Fausto J. Pinto Conselho Editorial: Prof. Doutor Fausto J. Pinto, Profª. Doutora Ana Sebastião, Prof. Doutor Mamede de Carvalho, Prof. Doutor António Vaz Carneiro, Prof. Doutor Miguel Castanho, Dr. Luís Pereira  Equipa Editorial:  Ana Raquel Moreira, Cristina Bastos, Isabel Varela, Joana Sousa, Maria de Lurdes Barata, Rui Gomes, Sónia Teixeira  Colaboração:  Gabinete de Relações Públicas, Internacionais e Comunicação  Versão Inglesa: AP|PORTUGAL- Language Services  Conceção: Metatexto, Lda. e-mail: news@medicina.ulisboa.pt  Sede do Editor e Sede da Redação: Avenida Prof. Egas Moniz, 1649-028 Lisboa Estatuto Editorial Anotado na ERC 

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