Polaryx’s drug candidates are intended to treat lysosomal storage disorders, where cellular toxic wastes are responsible for the disease pathogenesis.
Our Science
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 small molecule 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 13 genetically distinct subtypes categorized according to the associated gene (CLN1–8; CLN10–14). The three most common forms of NCLs are CLN1, CLN2, and CLN3. NCL is generally characterized by the excessive accumulation of lipofuscin, which may result in lysosomal dysfunction and cause devastating neurodegeneration.
Despite being genetically heterogeneous, NCLs share similar histopathological and clinical characteristics and clinical manifestations of NCLs include progressive mental deterioration, cognitive impairment, visual failure, seizures, and deteriorating motor function.
Of the 13 NCL sub-types, only one, CLN2, has an established standard of care in the form of an enzyme replacement therapy. |
Krabbe DiseaseGloboid-Cell Leukodystrophy (GLD) |
Krabbe disease, also known as globoid cell leukodystrophy, is caused by mutations in the GALC gene, leading to galactocerebrosidase deficiency and an inability to break down certain lipids in the body. This results in accumulation of toxic substances in the brain and other areas of the nervous system leading to demyelination and severe neurological decline.
The incidence rate of Krabbe disease varies significantly, affecting 0.3 to 2.6 per 100,000 live births.
Hematopoietic stem cell transplantation (HSCT) is considered the current standard of care. |
Tay-Sachs and Sandhoff DiseasesGM2 Gangliosidoses |
Tay-Sachs and Sandhoff Diseases are part of a group of inherited disorders called GM2 gangliosidoses, resulting from deficiencies in the hexosaminidase enzyme. This mutation leads to an accumulation of GM2 ganglioside in nerve cells, resulting in rapid neurodegeneration.
The prevalence of Tay-Sachs disease is approximately one in 100,000 births, while Sandhoff Disease is much rarer with a prevalence of approximately 0.67 per 100,000 births.
There is currently no established standard of care for these diseases. |
Niemann-Pick Disease
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NPD is caused by mutations in the SMPD1 gene. This causes acid sphingomyelinase enzyme deficiency, leading to lipid accumulation in multiple organs, including the brain.
The prevalence for NPD types A and B is one in 250,000 births, with a high prevalence found within the Ashkenazi Jewish population.
An enzyme replacement therapy has been approved for the treatment of NPD type A and type B, but is not intended to treat neurological symptoms. |
Kim et al., 2017
We’re seeking partners to help bring Polaryx therapies to patients and families fighting lysosomal storage disorders.
Interested?