ECNP New Frontiers meeting 2018: In a nutshell

This year, the ECNP New Frontiers meeting (18-19 March, Nice, France) provided a unique platform of discussion for scientists, industry leaders and regulators engaged in addressing the hard challenge to find therapies to neurodevelopmental disorders (NDDs), such as Fragile X syndrome and autism, which are among the diseases with the highest unmet needs in the current medical landscape.

New promising drugs, such as metformin1, might open the door to new therapies to treat NDDs like Fragile X syndrome. Important advancements in biomolecular technologies, such as CRISPR-Cas9 for gene editing, also provide us with powerful and unprecedented tools to get more insights in the pathophysiological mechanisms underlying such disorders. Data from genetics, animal studies, pharmacological approaches and more indicate that different brain disorders may have their roots in the early childhood or even before, during the prenatal development of the brain. Nevertheless, finding the right candidates to target -- a gene or a cellular pathway -- is only the first step towards the therapy. After defining “what”, we need to establish when to intervene and which regions of the brain are mostly involved in the biology of the disease: different data indicate that there is a specific window of opportunity for the therapeutic intervention (“what, when, where”) -- a key aspect to define if we want to obtain the most benefits for the patients.

The way forward
Despite the progresses in understanding the NDDs, further efforts are needed: the “valley of death” in translating preclinical findings to clinical effects has been in fact particularly “fatal” for many molecules studied to treat NDDs. To bridge such valley, new approaches need to take place: clinical trials based on reproducible preclinical data obtained in more than one species, new readouts in preclinical and clinical studies to be used to investigate the effects of specific compounds are just two of the several examples discussed at the meeting.

One of the most striking take-home messages was that early interventions in patients might be the key to successfully treat NDDs: data suggest that “the sooner, the better”. However, should clinical trials for neurodevelopmental diseases being conducted first in children? And what are the most important ethical aspects to consider? The regulatory environment is less well established compared to that for the research conducted on other diseases: this represents an important issue for researchers engaged in designing a clinical trial.

1. Dy, A.,B.,C., Tassone, F., Eldeeb, M., Salcedo-Arellano, M., J., Tartaglia N., Hagerman R. Metformin as targeted treatment in fragile X syndrome. Clin Genet. 2018 Feb;93(2):216-222.