Lysosomes are central to eliminating cellular toxic wastes and play an integral part of cellular signaling pathways. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, coordinates the functionality and activity of lysosomes in the cell. As a result, boosting lysosomal biogenesis through TFEB upregulation is an attractive therapeutic intervention for lysosomal storage disorders.
Studies in animal models and human primary astrocytes have demonstrated the role of our drug candidates, PLX-100, -200, and -300, as PPARα agonists that can upregulate TFEB expression and promote lysosomal biogenesis. They also reduce inflammation in the brain, promote neuronal survival, and improve motor functions. Our intranasal gene therapy candidate, PLX-400, has been shown to increase lifespan in murine models.
Batten DiseaseNeuronal Ceroid Lipofuscinosis (NCL) |
NCL, also known as Batten disease, is a group of 14 rare inherited lysosomal storage disorders affecting 1-4 children/100,000 live births. The major characteristic of NCL is an excessive accumulation of auto-fluorescent lipofuscin in both neuronal and other cells in the patients. |
Krabbe DiseaseGloboid-Cell Leukodystrophy (GLD) |
Krabbe disease, or globoid-cell leukodystrophy (GLD), is a rare inherited lysosomal storage disorder that affects 1 in 250,000 live births. |
Niemann Pick Disease
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Acid sphingomyelinase deficiency, including Niemann Pick Disease types A and B, is a type of lysosomal storage disease caused by genetic mutations in the acidic sphingomyelinase (ASMase) enzyme. |
Batten Disease presents as seizures and/or vision failure followed by progressive motor dysfunction and cognitive decline.
Kim et al., 2017