PhD in Computational Biology and ICREA researcher.
Aloy and his team have taken part in European projects like SyStemAge to study ageing in human stem cells, and they have also carried out their own researches like the one on how to detect and prevent drug side effects.
Patrick Aloy, PhD in Computational Biology and ICREA researcher, leads the Structural Bioinformatics and Network Biology laboratory at the Institute for Research in Biomedicine (IRB Barcelona) and is heading up the "SysPharmAD" project to identify new biomarkers, therapeutic targets and compounds that can stop the progression of Alzheimer’s disease. Last month, the project received a Consolidator Grant from the European Research Council for €1,300,000 for the next five years.
How will network biology help better understand Alzheimer?
We hope to contribute overall knowledge of a disease that is highly complex and involves many molecular and cellular factors that had previously been dealt with separately. We don’t want to tackle amyloid pathology or mitochondrial dysfunction individually. We want to create a unique map that will allow us to join all the different physiological cell processes together and, from there, seek out the best points to monitor and intervene. This means finding the molecules that can serve as biomarkers and getting new therapeutic targets.
How will these biomarkers be used to impact the disease?
Identifying the markers will allow us to monitor, for example, individual response to specific treatment in each patient, cutting the costs of clinical trials and improving results. We could know whether or not a patient is responding to treatment in a shorter period of time and would know if we are truly modifying their biology and, thus, stopping the disease from progressing.
The aim is to stop the disease?
Yes, what we need in terms of Alzheimer is to be able to modify the biology of the disease through drugs and stop it from advancing. What we can't do is reverse it. However if we identify better biomarkers than the ones we have now, we’ll be able to diagnose it earlier, before clinical symptoms become apparent. So, if we’re able to stop it in that early stage, we’ll have gained a lot of ground.
How can we reach this early detection?
There are already biomarkers that allow us to identify some molecules using a lumbar puncture for cerebrospinal fluid or using PET (positron emission tomography) techniques, but these are difficult and expensive. And, moreover, they are only preformed when patients display symptoms of a disease, which is still too late, as the brain has normally already been damaged. Additionally, there is a moderate correlation between the levels of the markers and the phenotype observed. If we could find more or less complex combinations of biomarkers more easily, in blood for example, early diagnosis would be possible before the first symptoms.
Does the "SysPharmAD" project expect to be able to define biomarkers through blood analysis?
Not in humans, but in mouse models for Alzheimer’s disease. Thanks to the global overview that we get through systems biology, we will work to find complex combinations of various molecules to create complex profiles of markers that tell us which stage of the disease the mouse is in.
We’re currently working on the first phase of the project with mice in various stages of the disease. We’re carrying out full genomic, transcriptomic and proteomic monitoring of the hippocampus and cortex of these mice. We will know the point to which they are altered in each stage of the disease. And from here, using interaction maps, we want to see how the disease evolves and produce mathematical models, create this model on the computer using the data from the mice and then see if we can transfer it to humans. No one has ever before developed dynamic models to represent the evolution of the disease on a molecular level.
And once you know this dynamic part of the disease?
From these mathematical models, from systems biology, we will be able to better understand the onset and progression of the disease and will move on to identify the points we can use to monitor which stage the disease is in and block it there so it doesn’t progress.
We’re talking about early detection and stopping the progression of the disease, but not preventing it. Is Alzheimer inevitable?
The main risk factor for Alzheimer is ageing and since our lifespan is constantly increasing, so will the number of people with this disease. The figures are clear; there are currently 35 million patients around the world and this number is expected to reach 50 million by 2025. For now, the best prevention is to lead a healthy life to help preserve the body and mind. There are studies that show that people with higher studies who continue to keep their brain active suffer from less or later cognitive deterioration.