Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Inborn Errors of Metabolism (iPSC-IEM)

Study Overview
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Brief Summary
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Human induced pluripotent stem cells (iPSCs), are reprogrammed from somatic cells that can self-renew indefinitely and produce different types of cells. They provide human model cell lines for orphan drug development. It is the goal of this study to define new cellular disease models for Inborn Erors of Metabolism, as enabling tools for both drug discovery and development.

Official Title
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Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Inborn Errors of Metabolism, an International, Multicenter Study

Conditions
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Inborn Errors of Metabolism

Intervention / Treatment
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* Other: Skin biopsy
* Other: Withdraw of blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent is obtained from the participant or from the parent/ legal guardian The participant is aged between 2 months and 50 years The diagnosis of an Inborn Error of Metabolism (IEM) is genetically confirmed by Centogene The participant is a first-degree or a second-degree relative of an individual with Inborn Error of Metabolism (IEM) genetically confirmed by Centogene Exclusion Criteria: Inability to provide informed consent The participant is younger than 2 months or older than 50 years The diagnosis of an Inborn Error of Metabolism (IEM) is not genetically confirmed by Centogene and The participant is not a first-degree or a seconddegree relative of an individual with Inborn Error of Metabolism (IEM) genetically confirmed by Centogene Previously enrolled in the study

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with an Inborn Error of Metabolism<br> | Other: Skin biopsy<br>* The biopsy will be performed by means of punch biopsy (diameter 2.5 mm) under local anesthesia on a forearm. The skin biopsy will be transferred to sterile cell culture Dulbecco's Modified Eagle Medium (DMEM) 1% Penicillin 1% Streptomycin 1% Gentamycin medium 10% FBS.<br>Other: Withdraw of blood<br>* Blood will be collected in: 1 x Ethylene Diamine Tetraacetic Acid (EDTA) tube (7.5 ml) - for further leucocytes extraction that are a potential backup for new iPS cell lines generation 1 x Citrate Phosphate Dextrose Adenine (CPDA) tube (8.5 ml) - for EBV-transformed lymphoblastoid cell lines generation 1 x Dried Blood Spot DBS-filtercard, called CentoCard® - for quality control confirmatory genetic testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Generation of patient-specific induced pluripotent stem cells and then differentiate them into neural cells. | To generate patient-specific induced pluripotent stem cells and then differentiate them into neural cells, or other specific cell according to the Inborn Error of Metabolism, to study the misfolded proteins in endoplasmic reticulum, their role in untranslated protein response, and possible mechanisms to shuttle the misfolded proteins into lysosomes. | 1 day |