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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders
Yaiza Díaz-Osorio1, Helena Gimeno-Agud1,2, Rosanna Mari-Vico1
1Synaptic Metabolism and Personalized Therapies Lab, Institut de Recerca Sant Joan de Déu, Department of Neurology and MetabERN; Esplugues de Llobregat, Barcelona, Spain.
Journal of Inherited Metabolic Disease
|January 22, 2025
Summary
Altered cell trafficking, a type of inherited metabolic disease, involves autophagy defects. Spermidine, an autophagy inducer, improved motor and cognitive symptoms in patients with SYNJ1 and NBAS gene mutations.
Area of Science:
- Cellular Biology
- Genetics
- Neurology
Background:
- Cell trafficking alterations are a significant category of Inherited Metabolic Diseases with diverse neurological symptoms.
- Understanding the pathophysiology of these monogenic disorders is crucial for developing new therapies.
- Autophagy dysfunction is emerging as a key targetable mechanism in these diseases.
Purpose of the Study:
- To investigate the role of autophagy in the pathophysiology of cell trafficking disorders caused by SYNJ1 and NBAS gene mutations.
- To assess the therapeutic potential of modulating autophagy in these conditions.
Main Methods:
- Assessed autophagic flux in primary fibroblast cultures from patients and controls.
- Utilized spermidine, an autophagy inducer, in in vitro studies.
- Conducted n-of-1 clinical trials to evaluate spermidine's efficacy in patients.
Main Results:
- Autophagy was identified as a hallmark in the studied cell trafficking disorders.
- In vitro treatment with spermidine demonstrated positive effects on autophagy.
- N-of-1 trials showed spermidine improved motor and cognitive functions in patients.
Conclusions:
- Autophagy alterations are a common feature in the pathophysiology of cell trafficking disorders.
- Targeting autophagy presents a promising therapeutic avenue for personalized treatment.
- Spermidine shows potential as a therapeutic agent for these conditions.
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