The paper “Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS” focuses on the investigation of astrocyte-secreted extracellular vesicles (EVs) and their role in motor neurone death in Amyotrophic Lateral Sclerosis. The study shows that EV formation and miRNA cargo are dysregulated in C9ORF72 patient-derived astrocytes and this affects neurite network maintenance and motor neurone survival in vitro.
In particular, professor Ferraiuolo has identified downregulation of miR-494-3p, a negative regulator targets involved in axonal maintenance. By restoring miR-494-3p levels through expression of an engineered miRNA mimic, we can partially rescue MN survival. Consistently, Laura also reports lower levels of mir-494-3p in cortico-spinal tract tissue isolated from sporadic ALS donors, thus supporting the pathological importance of this pathway in MNs and its therapeutic potential. In conclusion, the study provides evidence that manipulation of individual miRNAs can lead to significant beneficial downstream effects to be validated in vivo.
“I would like to thank the Instituto Paulo Gontijo and the Judging Committee for giving me the 11th Paulo Gontijo Award. Previous scientists who have been awarded this prize are eminent personalities in the field of MND, who have really contributed to the field in understanding the mechanisms leading to motor neuron death in this devastating disorder. I would also like to thank and this is where my deepest gratitude goes to really, is MND patients, their carers and all the donors who have contributed to my research, by donating skin samples blood and all sorts of bio samples, which are so key for our research.” Dr. Laura Ferraiuolo, PhD
About the winning research
Dr. Mamede de Carvalho, president of the Judging Commission, neurologist and neurophysiologist, professor of Physiologhy at the Medicine Faculty in Lisbon University, tells a little more about the winner and her research.
“Dr. Laura Ferraiuolo is a well-known Italian researcher who has worked in the United Kingdom at Sheffield University since 2004 as a professor. Investigating induced human astrocytes from 3 ALS patients carrying C9orf72 mutations and 3 unaffected donors, Laura and her team found an abnormal composition of extracellular vesicles released by the affected patients’ astrocytes, in particular by down-regulating miR-494-3p. In addition, with research, it has become clear that the restoration of miR-494-3p is neuroprotective for motor neurons, indicating great potential for testing new compounds in future trials”, says Mamede. Laura Ferraiuolo is the 5th woman to receive the Paulo Gontijo Award.
The Paulo Gontijo Award
The PG Award is a project of scientific support, aiming to the search of cause and cure of Amyotrophic Lateral Sclerosis (ALS). It is maintained by the Gontijo family in respect of the legacy left by the IPG founder, Paulo Gontijo, who died of the disease in 2002. In addition to the $ 20,000 incentive, the award-winning researcher receives a gold medal. The piece bears the mark of a renowned jewelry design, Carla Amorim, a partner and donor of her work to IPG.
The presentation of the winning work will occur at the opening session of the 30th International Symposium on ALS/MND. Dr Laura Ferraiolo research presentation will be in Perth, Australia, at December 4th, 2019.
The PG Award is a permanent initiative of Paulo Gontijo Institute, 100% financed by the Gontijo family, maintainer of the foundation. “I feel honored, once again, with the choice of the PG Award winner, which this year will be given to Dr. Laura Ferraiolo. It is with great pleasure that we reaffirm our recognition of scientific research and a significant study in search of the cause and cure of ALS. It is always a happiness for me to give the award to the researcher chosen by the jury, recognizing the results of the efforts and dedication of young researchers”, says Marcela Gontijo, IPG president.