Sjögren-Larsson Syndrome (SLS)

Sjögren-Larsson Syndrome (SLS) is a rare condition that constitutes an autosomal recessive disorder characterized by a clinical triad of ichthyosis, spastic movement disorder, and intellectual disability. It is further associated with various secondary features, the most remarkable being glistening white dots located in the retinal periphery. Protheragen is dedicated to the development of novel therapies aimed at preclinical drug stage for neurocutaneous disorders such as Sjögren-Larsson syndrome.

Overview of Sjögren-Larsson Syndrome

A rare hydrops fetalis, Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder with congenital ichthyosis, neurological spasticity, and intellectual disability secondary to mutations in the ALDH3A2 gene. The gene in question is responsible for fatty aldehyde dehydrogenase (FALDH), an enzyme primarily participating in lipid metabolism. FALDH plays the important function of oxidizing fatty aldehydes but, when defective, causes the accumulation of toxic lipids as well as oxidative stress and other systemically complicating factors. There is increasing evidence of renal lipid effects, such as tubular and nephrosis due to systemic lipid toxicity.

Pathogenesis of Sjögren-Larsson Syndrome

Sjögren-Larsson Syndrome pathology stems from biallelic mutations in the ALDH3A2 gene that cause the enzymatic deficit of fatty aldehyde dehydrogenase (FALDH). This disruption results in the accumulation of cytotoxic lipids that form Schiff base adducts within cells leading to oxidative stress, chronic inflammation, and tissue damage. Congenital ichthyosis, spastic paraplegia, and intellectual disability from systemic lipid toxicity in skin, brain, kidneys are the prominent features.

Fig.1 Overview of RECQL4, ANAPC1, DNA2, and CRIPT variants associated with RTS. (Rizzo et al., 2022)

Therapeutics Development for Sjögren-Larsson Syndrome

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen is focused on building a comprehensive ecosystem of preclinical research, providing consolidated services to expedite the development of new therapies for SLS. Sophisticated tools and methods of our specialists offer complex support from therapeutic development, diagnostics development to disease model development.

Therapeutic Development

• Small Molecule Drug
• Cell Therapy
• Gene Therapy
• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Diagnostics Development

• Biomarker Development
  Urinary 4-HNE
  Single-Cell ALDH3A2 Transcriptomics
• Diagnostic Kit Development
  ALDH3A2 NGS Mutation Panels
  Rapid ALDH3A2 PCR Kits

Disease Model Development

• Keratinocytes with ALDH3A2 Mutations
• HaCaT-ALDH3A2KO
• 3D Epidermal Organoids
• Conditional Aldh3a2 Knockout Mice
• Humanized ALDH3A2 p.Gly259Val Transgenic Mice

Drug Safety Evaluation & DMPK Services for Sjögren-Larsson Syndrome