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 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.

Polaryx’s drug candidates are intended to treat lysosomal storage disorders, where cellular toxic wastes are responsible for the disease pathogenesis.

our science

Batten Disease

Neuronal 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.

 

NCLs are inherited in an autosomal recessive pattern, and their frequencies vary based on the genetic mutations. Over 400 different mutations have been found in at least 13 different genes so far.

 

Symptoms include vision loss, seizures, motor and muscle dysfunction. Due to the non-specific symptoms, it is often misdiagnosed as one of the other neurological disorders.

Krabbe Disease

Globoid-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.

 

This autosomal recessive disease is caused by a deficiency in the galactosylceramidase (GALC) enzyme, leading to an altered catabolism of galactosylceramide and an increase in the level of the toxic glycolipid, psychosine.

 

Symptoms include irritability, spasticity and seizures. Despite conducting many studies, no effective drug is currently available to halt and/or delay the progression of GLD.

Niemann Pick Disease
Types A and B

Acid Sphingomyelinase Deficiency

Acid sphingomyelinase deficiency, including Niemann Pick Disease types A and B, is a type of lysosomal storage disorders caused by genetic mutations in the acidic sphingomyelinase (ASMase) enzyme.

 

Deficiencies in ASMase or its activity results in a reduced break-down and increased levels of intracellular sphingomyelin, leading to cellular dysfunction and cell death (particularly neurons and glial cells).

 

Similar to other LSDs, symptoms are non-specific and can include motor and muscle dysfunction, hearing and vision loss.

Batten Disease presents as seizures and / or vision failure followed by progressive motor dysfunction and cognitive decline.

Kim et al., 2017

We’re seeking partners to help bring Polaryx therapies to patients and families fighting lysosomal storage disorders.
Interested?