Within the United States, Orphan Drug designation is granted by the FDA to facilitate the development and review of drugs or biologics intended to treat rare conditions. In this case, “rare” is defined as affecting under 200,000 Americans. Once a drug developer receives Orphan Drug designation, the developer also earns a variety of other benefits, such as fee waivers, tax credits, increased regulatory assistance, and 7 years market exclusivity upon approval. According to a late August 2021 news release from biotechnology company Polaryx Therapeutics, Inc. (“Polaryx”), the company’s therapeutic candidate PLX-200 received Orphan Drug designation for the treatment of GM2 gangliosidoses (Tay-Sachs disease and Sandhoff disease).

PLX-200

So what exactly is PLX-200? According to Polaryx, PLX-200 is:

a repurposed drug…and PPARα agonist that boosts lysosome biogenesis via TFEB upregulation. It has therapeutic and/or prophylactic potential for Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL or CLN2) and for other NCLs, such as Juvenile Infantile Neuronal Ceroid Lipofuscinosis (JNCL or CLN3).

So, as you can see, Polaryx has already evaluated PLX-200 for a variety of other conditions. In other studies, PLX-200 has been shown to have neuroprotective properties. The treatment also reduced neuronal inflammation, reduced the accumulation of toxic material, stopped cellular apoptosis from occurring, and activated genes associated with lysosome production.

Currently, there are no safe or effective treatment options for patients with Tay-Sachs disease or Sandhoff disease. Most available treatments are symptomatic and supportive, rather than impactful towards the conditions’ underlying mechanisms. As Tay-Sachs and Sandhoff diseases are both fatal within the first few years of life, new treatment options are urgently needed. This Orphan Drug designation now offers Polaryx an avenue to move forward with additional studies and testing, hopefully to fill this unmet need.

Sandhoff Disease

Often compared to Tay-Sachs disease, due to similar symptoms, Sandhoff disease is a lipid storage disorder which negatively affects the central nervous system (CNS). HEXB gene mutations cause Sandhoff disease. This condition is inherited in an autosomal recessive manner, meaning patients must inherit one defective gene from each parent. Due to the genetic mutations, fatty substances called GM2 gangliosides accumulate in nerve cell lysosomes. This over accumulation becomes toxic, causing CNS damage and deterioration. Sandhoff disease highly affects those of Lebanese, Metis Indian, and Creole descent. Typically, symptoms appear within 3-6 months following birth; the condition is often fatal within a few years. Symptoms include:

• Lethargy
• Difficulty feeding or swallowing
• Cherry-red spots in the eyes
• Motor delays and weakness
• Developmental regression
• Exaggerated startle response
• Heart murmurs
• Vision loss
• Seizures
• Enlarged spleen

Learn more about Sandhoff disease here.

Tay-Sachs Disease

HEXA gene mutations cause Tay-Sachs disease, a rare inherited lysosomal storage disease. Normally, HEXA creates an enzyme which breaks down gangliosides. However, the mutations cause toxic levels of gangliosides to accumulate in the brain, causing brain and CNS damage. Symptoms often appear within 6 months following birth; the condition is fatal within a few years. Symptoms include:

• “Floppy” muscle tone
• Lethargy and listlessness
• Hearing and vision loss
• Cherry-red spots in the eyes
• Developmental regression
• Exaggerated startle response
• Seizures
• Dementia
• Muscle stiffness and paralysis

Learn more about Tay-Sachs disease here.