Mafalda Bourbon – group leader of the Cardiovascular Research Lab (at BioISI- Instituto Nacional de Saúde Dr. Ricardo Jorge) and her team – received 1 M€ from “la Caixa” foundation to develop an innovative project that brings together scientists, clinicians and people suffering from Familial Hypercholesterolemia aiming at improving the diagnosis and treatment as well as to provide clinicians better tools for their clinical practice regarding this condition.

Personalized medicine tools to improve early diagnosis of familial hypercholesterolemia is the title of the project that will be led by Mafalda Bourbon (on behalf of BioISI-INSA) in partnership with three other institutions: the University of Helsinki, the University Hospital Rotterdam and the University of La Réunion Medical School Saint Pierre (INSARM unit). These four research performing institutions have a clear ultimate goal: to create a model of care [1], providing  a set of digital resources, available at an  interactive website, to ensure that an individual receives the right diagnosis and the right treatment, at the right time, all over the world. The ultimate goal is that this model of care will be further on integrated in clinical practice all over the world to improve the life of individuals with this condition.

The major expected outcome – will be accomplished within the duration of the project (3 years) by means of the development of three main tasks. Researchers will make  efforts to improve the diagnosis and the treatment and, finally, building up the model of care itself, being the latter one informed by the conclusions found in the two first ones.

Familial hypercholesterolemia (FH) is a very common genetic condition (affecting 1/300 people) and is characterized for severely elevated low-density lipoprotein (LDL) – also known as the “bad cholesterol” – levels from birth, due to a deficiency in the LDL receptor protein. In turn, the accumulation of this compound in arteries can, for example, increase the risk of an early onset heart attack up to 20-fold, in individuals between 20 and 40 years old.

It is known that FH is associated to a defect in 3 genes, leading to the existence of nearly 6.000 different variants. However, around 3.000 of these variants are of unknown significance. In other words, from the 6.000 identified, half  are found in people with a clinical diagnosis of FH but the way they impact LDL receptor protein function remains unclear so their clinical  diagnosis is not confirmed. This is one particular aspect on which the project aims at filling the gap. According to Mafalda Bourbon: “The project proposes the characterization of all Portuguese variants and plan to achieve a definite classification in about 70% of all variants FH worldwide.” For this purpose, the research group coordinated by Dr. Simon Pfisterer from the University of Helsinki, will be of paramount importance since they established novel tools for automated quantification of intracellular lipid storage, which allows the analysis more than one variant at a time.

Concerning treatment, Mafalda Bourbon explains that: “There are several drugs available, but the condition manifests differently, according to the variant type present and the activity of the LDL receptor found, in a given patient.” This means that not all individuals with FH need the same kind of treatment. In this way, Dr. Gilles Lambert and his coworkers, from the University of La Réunion Medical School Saint Pierre, due to their experience in cell biology techniques and drug assays, will give important inputs in developing personalized therapeutic options. Consequently, “(…) treatment can be optimized in a way that each patient will receive the right treatment increasing its adherence and decreasing side effects.”, points out Mafalda Bourbon.

“We hear very often, from people with FH, that they are not included on finding the solutions for a better clinical management and care of their condition”, confesses Mafalda Bourbon. Taking this into account, the project includes an innovation way of building up the model of care to be further on applied in the clinical practice. It foresees a focus group with clinicians, scientists and, most importantly, people with FH, where they will be able to co-create the model of care to better respond to their needs and expectations. In this task, Dr. Eric Sijbrands – a clinician and researcher from University Hospital Rotterdam, and his team – will definitely be an added value due to their experience in the diagnosis and management of FH patients, along with FH Europe, a patients’ association, deeply involved in educational activities regarding this condition.

As a summary, Mafalda Bourbon refers that: “The project offers a scientific breakthrough to address key unmet clinical needs for more than 30 million individuals affected around the globe (…) and will reduce the burden – emotional, health, economic, societal – for the individuals, families, society and health care systems by enabling faster and correct diagnosis of the individual and their potentially affected relatives, which will inform more optimal disease management, preventing (further) cardiovascular disease and improving quality of life of an individual with FH. (…) For us this project means that we will be part of this change and that our work will save lives”.

The current edition of “la Caixa” health research call will support 11 biomedical research projects led by Portuguese universities and research centers (out of 152 applications spearheaded by Portuguese institutions), that, together, will receive a total of 7.9 million euros to tackle health challenges. FCT has associated the initiative and will support Portuguese institutions with matching funds in a total of 3.7 million euros Simultaneously, 22 projects led by Spanish institutions and research units were also selected, making a total of 33 projects recommended for funding within the call.

Learn more about the project here.

Find out more about Cardiovascular Research Lab here.

Discover more about “la Caixa” Health Research Call 2023 here.

PIs from the current project (from left to right): Eric Sijbrands, Mafalda Bourbon, Simon Pfisterer  and Gilles Lambert, at he public ceremony [photo provided by Mafalda Bourbon]

PIs from all the awarded projects, at “la Caixa” public ceremony [photo provided by Mafalda Bourbon] 

[1] Adapted from , accessed online, 4 December 2023