Periodic Reporting for period 1 - SIMPATHIC (Accelerating drug repurposing for rare neurological, neurometabolic and neuromuscular disorders by exploiting SIMilarities in clinical and molecular PATHology)
Reporting period: 2023-07-01 to 2024-12-31
Drug repurposing can fill an important gap for rare disease patient groups with large unmet medical needs. In comparison to traditional drug development, drug repurposing reduces the time and costs for drug development, regulatory approval, and market authorization. Yet, we need to increase the efficiency of the drug repurposing pathway to provide broader access to new therapeutic modalities for larger groups of patients. SIMPATHIC’s main objective is to accelerate drug repurposing for rare neurological, neurometabolic and neuromuscular disorders. SIMPATHIC’s main accelerating innovation is the simultaneous drug development for groups of patients with different genetic diagnoses but overlapping neurological symptoms and molecular pathomechanisms. SIMPATHIC’s key outputs accelerating the drug repurposing pathway include: Standard operating procedures for culturing stem cell-derived neuronal cell models with proven relevance for clinical symptoms and amenable to high-throughput drug screens; New drug repurposing candidates with proven efficacy in advanced brain-on-a-chip and 3D brain organoid models, as demonstrated by reversal of molecular biomarker signatures and cellular readouts associated with clinical symptoms; Designs of innovative basket clinical trials to which patients with different disorders are recruited, utilizing and aggregating personalized clinical endpoints; A training module for patients and patient organizations to empower them as drivers of the drug repurposing pathway; Blueprints for intellectual property strategies, business models, regulatory dossiers and patient access strategies, developed in co-creation between all relevant stakeholders. SIMPATHIC’s proof-of-concept for the simultaneous development of repurposed drugs for multiple indications will show the path forward to development of personalized treatment opportunities for groups of rare disease patients in a cost- and time-efficient manner.
-Established multidisciplinary collaborations between all relevant stakeholders (Multistakeholder advisory board)
-Developed induced pluripotent stem cell (iPSC) lines for nine rare neurological, neurometabolic and neuromuscular disorders (neuro-RD) established robust molecular and cellular readouts that reflect neurological symptoms and toxicity.
-Executed a pilot project with molecular omics profiling of iPSC-derived neuronal cell models to select the most appropriate omics technology for drug target and therapeutic biomarker identification
-Defined standardized operating procedure for fast NGN2-induced differentiation of iPSCs into neurons
-Established a platform for recording and publishing of FAIR metadata for SIMPATHIC's protocols and datasets.
-Finished the design of a training on drug repurposing targeting patient advocates.
-Clarified the high-overview design of the SIMPATHIC basket trial, identified the initial substudies to be included in the basket trial.
-Organized a survey and a series of interviews with patient representatives, clinicians and researchers to come to a set of patient reported outcomes (PROs) and patient reported outcome measures (PROMs) common to all neuro-RD (with additional disease-specific PROMs), to allow for borrowing of information on clinical efficacy across substudies and quantifying the impact on patients’ quality of life.
-Developed induced pluripotent stem cell (iPSC) lines for nine rare neurological, neurometabolic and neuromuscular disorders (neuro-RD) established robust molecular and cellular readouts that reflect neurological symptoms and toxicity.
-Executed a pilot project with molecular omics profiling of iPSC-derived neuronal cell models to select the most appropriate omics technology for drug target and therapeutic biomarker identification
-Defined standardized operating procedure for fast NGN2-induced differentiation of iPSCs into neurons
-Established a platform for recording and publishing of FAIR metadata for SIMPATHIC's protocols and datasets.
-Finished the design of a training on drug repurposing targeting patient advocates.
-Clarified the high-overview design of the SIMPATHIC basket trial, identified the initial substudies to be included in the basket trial.
-Organized a survey and a series of interviews with patient representatives, clinicians and researchers to come to a set of patient reported outcomes (PROs) and patient reported outcome measures (PROMs) common to all neuro-RD (with additional disease-specific PROMs), to allow for borrowing of information on clinical efficacy across substudies and quantifying the impact on patients’ quality of life.
The results beyond the state of the art will be reported later.