Where Ideas Grow

Pfizer awards grant to create a human model of sensory neurons

Researcher Marina Silva recently received funding of 137 thousand euros under the medical scholarship program of the pharmaceutical multinational Pfizer to work for 2 years to create a human model of sensory neurons, specifically the neurons that are affected by Familial Amyloidotic Polyneuropathy (FAP), also known as “the foot disease”. The objective is to decode what happens in neurons before the disease takes hold and then determine how to act preventively to stop neurodegeneration.

Familial Amyloidotic Polyneuropathy (FAP), now scientifically known as Transthyretin Amyloid Polyneuropathy (ATTR-PN), is a rare genetic disease caused by mutations in the protein Transthyretin (TTR) which causes this protein to be deposited in sensory neurons causing neurodegeneration. FAP affects approximately 10 thousand people worldwide and has a significant impact in Portugal with around two thousand patients, equivalent to 20 percent of patients worldwide.

Therapeutic options for FAP include liver transplantation (the organ where the TTR protein is synthesized) and strategies to stabilize or silence TTR, with the aim of slowing the progression of the disease. However, these options do not reverse the neurodegeneration already caused by the deposition of TTR in peripheral nerves, that is, they do not cure existing injuries. The objective of Marina Silva, who is part of the team led by Márcia Almeida Liz, from the i3S “Nerve Regeneration” group, is “to discover the mechanisms that initially occur in the disease and to better characterize progressive neurodegeneration to find new therapies that can be applied before the disease takes hold”.

Studies have already been carried out on some tissues such as the liver, adipose tissue and salivary glands of patients, but Marina Silva intends to study sensory neurons, the type of cell affected by this clinical problem. To do this the team will use cells from patients with FAP to “generate pluripotent cells (iPSCs), that is, cells that can be differentiated into various types of cells, and ‘create’ human sensory neurons to study the disease in its initial stages and monitor the changes that TTR is causing’, she explains.

This study, highlights Marina Silva, ‘will significantly increase knowledge about FAP, in addition to being an impetus for the future development of new therapies for the disease’. The results obtained will then be validated using biopsy samples from patients, as part of a collaboration with doctor Ricardo Taipa, from the Neuropathology Unit of the Centro Hospitalar Universitário do Porto. The project also includes the participation of researchers Pascal Röderer and Oliver Brüstle from Germany.