Seven partners from 6 countries including FGA and ESCO will develop new strategies using cellular assays based on IPSC-derived patient neurons and biomarker analyses.
SNAREopathies are a group of recently recognized rare neurodevelopmental disorders caused by mutations in eight genes that together drive secretion of chemical signals in the brain. Within 20 years, SNAREopathy incidence rose from zero to one of the most prevalent rare diseases to date (1:30k), producing a phenomenal unmet need.
The iSNARE consortium aims to change this situation by combining cellular assays based on available IPSC-derived SNAREopathy patient neurons with in vivo assays using available SNAREopathy mouse models. These in vitro and in vivo assays are combined in a standardized, integrated framework to systematically test and compare candidate treatments in three phases of development:
(i) four small molecules currently tested off label in small patient cohorts (replication study)
(ii) 6-10 emerging candidates (small molecule, antisense oligonucleotides)
(iii) novel compounds designed de novo by iSNARE in silico modeling using validated SNARE protein templates.
This systematic, multi-level approach will produce a unique data set that quantitatively compares effectivity and potency of most candidate treatments currently on the radar and firmly establishes the most promising ones. The strong connection to national treatment sites in nine EU countries + Israel ensures their rapid dissemination to clinical practice. The standardized array of in vivo and in vitro assays developed here provides a valuable framework for the assessment of future candidate therapies.
The iSNARE consortium (3 female, 4 male partners, 6 countries) brings together some of the best-cited scientists in the SNARE field and human neuron pioneers with experienced SNAREopathy mouse model experts, in silico modelling experts and patient organizations in nine EU countries + Israel. Together, this complementary expertise and patient participation warrant a project design that exploits the most recent scientific advances to promote new therapy development that maximally serves the patients’ needs.