Dr. Fernanda De Felice leads research line at IDOR that investigates central nervous system pathologies through biochemical markers

Neuroscience, one of the main and oldest areas of research at the D’Or Institute for Research and Education (IDOR), is a broad field of investigations into the human brain, studying from evolutionary factors such as the origin of feelings, to clinical alterations caused due to congenital, infectious or degenerative diseases. 

At IDOR, a large segment of this area is dedicated to neurodegenerative processes such as Alzheimer’s Disease and long-term neurological damage caused by COVID-19. All these studies share a common goal: to identify and measure alterations in the Central Nervous System (CNS) that can serve as a pathway to new therapies. Those are the focus of the research line led by Dr. Fernanda De Felice, neuroscientist and molecular scientist at IDOR. 

Sitting in her office, with light clothes and a sunny day, it is almost possible to forget that she’s by videoconference, from the other hemisphere of America. The time zone of Southeastern Brazil is similar to that of Ontario, Canada, where De Felice also conducts research at the Queen’s University, in partnership with IDOR. “One of the projects I’ve been working on at IDOR is the search for molecular biomarkers, both for Alzheimer’s disease and the neurological manifestations associated with COVID-19”, she summarizes. 

The researcher explains, however, that there is a great challenge in the search for these molecular markers located in the brain: the blood-brain barrier. She exemplifies that, in a neuroimaging study, another investigative line of IDOR, it is possible to see alterations in the brain structure of patients without major obstacles, but to understand chemical scenarios that occur inside the skull, the usual process of sample collection is invasive, as the brain is protected by the blood-brain barrier, which prevents the free molecules traffic between the brain and the blood circulation. In this way, many biomarkers are prevented from leaving the brain environment in large quantities into the bloodstream. 

“In the blood, you collect a sample and identify what is happening in the whole body, in general. But to know what’s going on in the brain, you need to do a lumbar pulse, collecting the cerebrospinal fluid (CSF). And we do that here at IDOR. But it is an invasive process, and one of our ambitions, both in research and to establish it in the long-term clinical routine, is to see these brain biomarkers through the blood”, explains the scientist.

In the investigation conducted by Dr. Fernanda De Felice, the challenge is that in the CSF there is a good concentration of markers to identify Alzheimer’s Disease at an early stage, but when this concentration passes into the blood, this information is very diluted. There is still no equivalence in the scientific literature between the values found in the CSF and those identified in the blood. The consensus on this equivalence of values is an ongoing international scientific effort, joined by IDOR, and which will enable earlier detection of Alzheimer’s Disease through less invasive tests. “And we’re moving towards it!” she says, confidently. 

On several fronts 

In addition to investing in the future of less invasive exams, both in Alzheimer’s Disease and neurocovid (neurological complications caused by COVID-19), Dr. De Felice focuses on the analysis of small components, the extracellular vesicles, which are produced by all cells in the body, including brain cells. These vesicles, secreted by the cells, hold within them the signature of the parent cell and important biomarkers. Most conveniently, they are able to cross the blood-brain barrier, going from the brain’s environment to the blood with information that gives clues to the brain’s biochemistry. “We are developing a methodology for isolating vesicles derived from neurons to look at disease biomarkers that reflect what’s happening in the brain”, reveals the researcher. 

When it comes to Alzheimer’s Disease, De Felice is not satisfied with a single line of investigation. It is not by chance that she won the Inge Grundke-Iqbal award in 2021, considered the Nobel Prize for research on the subject. This recognition resulted when, in another line of the scientist, her group investigated the hormonal markers of the disease. 

At the time, the researcher’s team identified that patients with Alzheimer’s had a deficiency in hormones signaling, such as insulin, GLP-1 – a hormone produced by the intestine and controls satiety – and irisin. This last hormone is secreted mainly with the practice of exercises, and led to the hypothesis that regular physical exercises throughout life could reduce or delay the chances of developing Alzheimer’s, in addition to opening ways to understand how the disease responds to therapies that aim increase the levels of this hormone in patients, a theory that has already shown promise in studies that the group carried out in animal models. 

“My group has been studying how deficient signaling of some hormones can be important in the disease, and we try to reverse the problems by increasing this hormonal signaling. What we understand is that Alzheimer’s patients have a signaling deficiency. We still don’t know if the disease causes this or if this factor favors the development of the disease, but it is a promising line. And irisin is physiologically present in extracellular vesicles, so at IDOR we are also trying to produce irisin-rich vesicles. The blood-brain barrier prevents many things from reaching the brain, to protect it, and that becomes a challenge when we try to treat it with medication. These vesicles, however, would be able to cross the barrier and supply irisin to CNS cells. At IDOR, we also have a project to increase the level of irisin in mesenchymal cells [stem cells with a great capacity for repairing body tissues] and use its therapeutic potential to increase irisin levels in the brain.” 

A long history with IDOR 

Dr. Fernanda de Felice says that, long before officially becoming a researcher at IDOR, she already had a decade of experience with the institution marked by scientific collaborations in studies on biomarkers and patients with dementia, sharing since then the authorship of several publications. 

At the beginning of the COVID-19 pandemic, in 2020, these ties became even closer with the discovery that the disease also affects the CNS, and a line of research dedicated to this investigation was created at IDOR. “We joined a lot of wills and strengthened this partnership. We were one of the first to publish about neurocovid. And from then on, we can say that I became an official researcher at IDOR, despite considering myself affiliated with IDOR since the beginning of its activities”, she says with a smile. 

But what the researcher highlights as a differential in her partnership with the institution is the possibility and, most importantly, IDOR’s interest in developing translational research, that is, research that unites information from basic science, carried out in the laboratory, with clinical research. “IDOR brings this possibility of partnering with clinical research, which is essential for researchers with the same interests as mine, which is to try to really understand the disease coming down to the patient’s level. For me, there’s no point in studying animal and cell models if it doesn’t reflect later on what’s happening with the patient. And on the other hand, by looking at patients’ outcome you can go back to the lab and improve experiments. This connection of the two worlds is very important. And IDOR offers that”, concludes the scientist. 

The reach of Rede D’Or is also a relevant point in the development of research on the CNS, as is IDOR’s Applied Neuropsychology Center (CNA), which, in addition to providing care, also develops research focusing on dementia and other neurodegenerative diseases. Find out more about our researchers and research lines on IDOR’s Neuroscience page. 

Written by Maria Eduarda Ledo de Abreu.