Medical need: MD1 is a type of muscular dystrophy that affects the muscles and other body systems. Its classic form is characterized by muscle weakness and wasting, prolonged muscle tensing, cataract, and often, abnormal heart function. Adults with the classic form often become physically disabled and have a shortened life span. MD1 is inherited in an autosomal dominant manner and is caused by mutations in the DMPK gene. There is currently no disease specific treatment option available

Goal:

Goal: The program aims for development and implementation of  physiologically highly-relevant cellular disease models (assays). Assay development is based on human differentiated induced pluripotent stem cells (iPSC), and goes with tailored AI-based image analysis methodologies. The assays are rendered applicable for HTS-HCS, and will be used for the development of disease modifying treatments.

Development stage: Large scale screening ongoing

Medical need: With a prevalence of 4:10,000, Dilated Cardio Myopathy (DCM) is the most common hereditary heart disease. It is characterized by chamber dilatation with thinned chamber walls, combined with a reduction in the ejection fraction. DCM usually leads to the clinical picture of heart failure. The only curative therapy so far is cardiac transplantation, which is limited to severely symptomatic DCM patients. DCM is often familial, and the most common genetic predisposition is a truncating variation in the giant sarcomeric protein, titin, which occurs in up to 15% of ambulant patients with DCM and 25% of end-stage or familial cases.

Goal: The program aims for development and implementation of a phenotypic approach exploiting a physiologically highly-relevant disease model in assay format. The assay goes with a tailored AI-based image analysis tool and will be used for the identification of new targets and small molecules targeting the sarcomere stability in cardiomyocytes derived from dilated DCM patient-specific iPSC.

Development stage: Pharmacological assay validation and automation

Medical need: Schizophrenia is a chronic and severe mental disorder affecting 20 million people worldwide. Schizophrenia is characterized by distortions in thinking, perception, emotions, language, sense of self and behaviour. Common experiences include hallucinations (hearing voices or seeing things that are not there) and delusions (fixed, false beliefs). Worldwide, schizophrenia is associated with considerable disability and may affect educational and occupational performance. There is a big medical need as currently available medications for Schizophrenia can cause serious side effects which is the major reason why many patients are reluctant to take them.

Goal: The project aims for the development and implementation of a phenotypic approach exploiting a physiologically highly-relevant iPSC-based cellular disease model in assay format, applicable for screening purposes with the opportunity to deliver lead chemical matter and/or identify new molecular targets and biomarkers for the development of personalised treatments of Schizophrenia.

Development stage: The assay is currently validated through a set of therapeutic molecules.

Medical need: SMARCA4 mutations have been identified in a high percentage of NSCLCs (up to 30%), and, to a lower extent, in other tumor entities with unmet medical need. SMARCA2 and SMARCA4 are subunits within the chromatin, functioning as an epigenetic regulator that opens and closes chromatin by shifting the positions of histones, helping to turn gene expression on and off. SWI/SNF subunits are frequently found to be mutated in different cancer entities. Several independent synthetic lethality screens identified SMARCA2 as being essential for the growth of tumor cells that harbor loss of function mutations in SMARCA4. 

Goal: The project aims for development and implementation of a phenotypic approach exploiting a physiologically highly-relevant disease model and the identification of small molecules targeting SMARCA2 as a tumor driver in SMARCA4-deficient cancers.

Development stage: Hit validation

Medical need: Parkinson’s disease (PD) is the second most common neurodegenerative disorder currently affecting between 7-10 million people worldwide. The annual cost of PD in Europe is in excess of 14 billion euros (Olesen et al, Eur J Neurol, 2012). SNCA mutations are associated with autosomal dominant forms of PD. SNCA is deemed as one of the major causative genes in different neurodegenerative disorders.

Goal: The program aims for development and implementation of  physiologically highly-relevant cellular disease models (assays). Assay development is based on human differentiated induced pluripotent stem cells (iPSC), and tailored AI-based image analysis methodologies. The assays are rendered applicable for HTS-HCS, and will be used for the development of disease modifying treatments.

Development stage: The assays have been validated through a set of compounds and are currently automated.

Medical need: Approximately 1 % of children is diagnosed with Autism spectrum disorder (ASD). ASD is a complex developmental condition that involves persistent challenges in social interaction, speech and nonverbal communication, and restricted/repetitive behaviour. ASD has multi-factorial origins with a strong genetic influence. SHANK3 is a leading autism candidate gene, with mutations occurring in between 1-2 % of individuals with ASD. SHANK3 encodes a protein that is essential for proper functioning of the synapse, the junction between neurons. There is currently no medication to treat ASD

Goal: The project aims for development and implementation of a phenotypic approach using cortical neurons derived from human stem cells(hESCs) deficient in the Shank3 gene. Its final goal is the identification of novel chemical matter for the treatment of ASD

Development stage: HCS-HTS pilot study

Medical need: Myofibrillar myopathies are a group of rare genetic neuromuscular disorders that may be diagnosed in childhood but most often appear after 40 years of age. Various genes responsible for MFM have been identified. Desminopathy leads to an early onset of the disease (20 – 30 years). Conditions are highly variable but are characterized by a slowly progressive muscle weakness. A weakening of the heart muscle (cardiomyopathy) is common and manifests as arrhythmia, conduction defects and eventually congestive heart failure. There is no disease specific therapy available

Goal: The project aims for development and implementation of a phenotypic approach exploiting a physiologically highly-relevant disease model based on iPSCs derived from MFM patients with mutations in DESMIN differentiated into cardiomyocytes for the development of disease modifying treatments

Development stage: Disease Model Validation