Smith-Lemli-Opitz Syndrome (SLOS)
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder caused by mutations in the DHCR7 gene. Leveraging our pioneering efforts in SLOS research, Protheragen is at the forefront of developing cutting-edge therapies to enhance the effective management of SLOS. As your trusted partner in SLOS drug development research, we provide unparalleled support to meet your research needs.
Overview of Smith-Lemli-Opitz Syndrome (SLOS)
Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder of cholesterol biosynthesis, first described in 1964 by Smith, Lemli, and Opitz. The condition arises from mutations in the 7-dehydrocholesterol reductase (DHCR7) gene, which disrupts the final step of cholesterol synthesis, leading to elevated 7-dehydrocholesterol (7-DHC) and severely reduced cholesterol levels.
Fig.1 Hedgehog (Hh) signaling is affected in Smith-Lemli-Opitz syndrome (SLOS). (Chattopadhyay A, Sharma A., 2023)
Pathogenesis of Smith-Lemli-Opitz Syndrome (SLOS)
Smith-Lemli-Opitz syndrome (SLOS) is caused by biallelic mutations in DHCR7, encoding 7-dehydrocholesterol reductase, which disrupts the final step of cholesterol biosynthesis. This results in a dual pathogenic mechanism: (1) cholesterol deficiency, impairing embryonic development (particularly Hedgehog signaling) and neuronal function, and (2) toxic accumulation of 7-dehydrocholesterol (7-DHC) and its oxidative derivatives, which induce oxidative stress and cellular damage in multiple organ systems. The resultant biochemical imbalance underlies the syndrome's characteristic malformations, neurodevelopmental deficits, and progressive multisystem dysfunction.
Fig.2 Schematic illustrating hypothetical mechanisms underlying retinal degeneration in the AY9944-induced rat model of Smith-Lemli-Opitz syndrome (SLOS). (Fliesler S J, Xu L., 2018)
Therapeutic Development for Smith-Lemli-Opitz Syndrome (SLOS)
Current management focuses on cholesterol supplementation to address deficiency, while statins are being investigated to reduce toxic 7-DHC accumulation. Supportive care targets multisystem complications, with emerging therapies like antioxidants and gene therapy under study. Treatment remains symptomatic as no cure exists.
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Simvastatin | Competitive inhibition of HMG-CoA reductase, reducing 7-DHC production | HMG-CoA reductase | Phase II |
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
As a leader in rare neurometabolic disease research, Protheragen offers comprehensive preclinical services to advance Smith-Lemli-Opitz syndrome (SLOS) therapeutics from discovery to validation. Our specialized platforms integrate genetic analysis and disease-specific modeling to replicate disease pathology with high fidelity. Using advanced blood-brain barrier (BBB) models, we optimize central nervous system (CNS) drug delivery while evaluating neuroprotection and off-target effects.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
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To advance the commercialization of novel therapies for Smith-Lemli-Opitz syndrome (SLOS), Protheragen provides comprehensive preclinical research services, covering pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Chattopadhyay A, Sharma A. Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis[J]. Frontiers in Molecular Biosciences, 2023, 10: 1120373.
- Fliesler S J, Xu L. Oxysterols and retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome: implications for an improved therapeutic intervention[J]. Molecules, 2018, 23(10): 2720.