Polaryx Therapeutics Inc recently issued the following announcement.
Polaryx Therapeutics Inc, a biotech company developing patient-friendly small molecule therapeutics for lysosomal storage disorders, such as Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) and other forms of NCL, announced that the Company has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for the treatment of patients with LINCL.
Neuronal Ceroid Lipofuscinoses are a group of autosomal recessive neurodegenerative lysosomal storage disorders. Among them, LINCL is caused by gene mutations in cln2 leading deficiency/loss of tripeptidyl peptidase 1 (TPP1) enzyme function, which is pivotal for degrading peptides. Subsequent intracellular accumulation of abnormal auto-fluorescent lipoproteins results in deterioration of neurons in the brain. Such accumulations also occur in other organs and can lead to loss of organ function, such as the retina. Because many patients suffer from vision loss, severe seizures, and declining motor function, leading to premature death, treatment for this disease is indeed an unmet medical need. The company has advanced a unique repurposing drug development strategy to provide patients with a safe and effective oral treatment option.
"The PLX-200 IND filing is a major development milestone for the Company. We will start the trial and confirm its safety and efficacy with CLN2 patients as soon as possible," says Dr. Hahn-Jun Lee, M.Sc., Ph.D., President and CEO of Polaryx Therapeutics, Inc.
Dr. Kalipada Pahan, Ph.D., Professor of Neurological Sciences, Biochemistry, and Pharmacology and the Floyd A. Davis, M.D., Endowed Chair in Neurology at the Rush University Medical Center in Chicago, also stated that "The IND filing of PLX-200 to the FDA for the clinical study on LINCL is indeed a big advance toward confirming our preclinical scientific studies and is a great step toward applying PLX-200 to other types of NCL, such as the juvenile form."
Polaryx Therapeutics, Inc.
Polaryx Therapeutics, Inc is dedicated to developing drug candidates for lysosomal storage disorders, for which there is currently no safe and patient-friendly treatment option available. Lysosomal storage disorders are a group of rare inherited genetic disorders caused by the dysfunction of lysosomal enzymes and/or molecules important in the function of these and other enzymes. Many children are victims of these devastating diseases and die at a young age due to lack of treatment options. Polaryx is repurposing existing safe oral medications or developing new drugs, so that the treatment is patient-friendly for a prolonged use.
PLX-200 is a repurposed drug that binds to peroxisome proliferator-activated receptor alpha (PPARα) to up-regulate the expression of TPP1 mRNA in brain cells via the PPARα/RXRα heterodimer. PLX-200 also enhances the production of transcription factor EB (TFEB) in brain cells via PPARα. TFEB then binds to the promoter of genes involved in lysosome biogenesis and activates their production to reduce the accumulation of lipofuscins. TFEB can regulate lysosomes due to its effects on the expression of lysosomal genes. PLX-200 also reduces inflammation and prevents cell death (apoptosis), which are important pathways that exacerbate the NCLs.
Late Infantile Neuronal Ceroid Lipofuscinosis
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL or CLN2) is caused by deficiency and/or loss of TPP1 caused from mutations in the Cln2 gene. TPP1, is a soluble 46 kDa acid protease found in the lysosome that removes tripeptides from the N-terminus of peptides. Cln2 gene mutations result in a deficiency and/or loss of function of the TPP1 enzyme, which leads to the intra-lysosomal accumulation of auto-flourescent lipofuscin. This leads to seizures, regression in developmental milestones, ataxia, visual impairment, motor deterioration, dementia, and early death between six years of age to early teenage years.
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