PerMed FH aims to bring personalised medicine protocol integrating all dimensions, from clinical diagnosis to molecular diagnosis to functional genomics. We will also provide evidence that functional assays, apart from being essential for determining variant pathogenicity, can be used to tailor the therapeutic strategy for FH patients.
Bringing personalised medicine to patients with FH relies on the development of dedicated tools and the use of patients’ genetic information to guide decisions during the prevention, diagnosis, and treatment phases.
Establishing a high-throughput pipeline for variant classification.
Developing a platform for drug optimisation tailored to individual genetic profiles.
Screening novel therapies targeting LDLR transport defects.
An interactive interface for querying and visualising ACMG-classified variants in key FH genes.
FH has been linked to variants in different genes. Majority of the cases concern the LDLR (low-density lipoprotein receptor) gene, but APOB (apolipoprotein B) and PCSK9 (proprotein convertase subtilisin/kexin type 9) genes can also be involved. With less than 10% of the variants functionally characterised, many patients are left without a definite diagnosis.
PerMed FH aims to establish a high-throughput pipeline for a fast functional profiling of variants in LDLR, PCSK9 and APOB variants will also be characterised. All variants will be classified and submitted to ClinVar for public access.
Current therapeutic solutions offered to heterozygous FH patients (the most common form of FH) rely on LDLR function. Therefore, it is crucial to identify variants and determine their impact on the LDLR function to adapt the treatment. Optimising pharmacotherapy according to genetic variant types, could bring large benefit for the management of FH patients, reducing therapeutic costs and avoiding drug interactions.
Permed FH also aims to investigate the repurposing of existing drugs and an innovative approach to find other treatments that can overcome a specific type of variants will be tested.
The results can, and should be, used in clinical practice in order to improve patient’s clinical outcome and quality of life.
Translating research findings into clinical practice is key. With PerMed FH, we plan to create evidence that will enable clinicians that once having the results of genetic testing, can recommend the most suitable therapeutic approach.
To establish the missing tools to design a personalised medicine model for FH, we will use a Delphi study −involving FH patients, healthcare professionals, and FH experts− and focus group to discuss project results and future implementation in health care.
With PerMed FH, we aim to have treatments optimised in a way that each patient will receive the right treatment improving the overall outcomes - increasing its adherence and decreasing side effects.
Dr Mafalda Bourbon Head of R&D, Instituto Nacional de Saúde Dr. Ricardo Jorge
PerMed FH offers a scientific breakthrough to address key unmet clinical needs for more than 30 million individuals affected around the globe. It will reduce not only the disease burden but also the emotional, economic, and societal burden – for the individuals, families, society and health care systems.
Magdalena Daccord CEO, FH Europe Foundation