Sanfilippo Syndrome Drug Discovery Service

Creative Biolabs is well-known in the field of neuroscience and has completed many innovative projects in this field. Now we are ready to provide one-stop research services against Sanfilippo syndrome for our clients all over the world.

Introduction to Sanfilippo Syndrome

Sanfilippo syndrome, also known as mucopolysaccharidosis (MPS) type III, refers to a rare autosomal recessive lysosomal storage disease that always affects the brain and spinal cord. This disease is caused by the accumulation of large sugar molecules of glycosaminoglycans (AKA GAG or mucopolysaccharides) and incomplete lysosomal degradation of heparan sulfate. The morquio syndrome can be divided into types A and B. Type A relates to a malfunction in the GALNS gene, while type B relates to a malfunction of the GLB1 gene. Depending on the subtype, patients with Morquio syndrome live between 20 and 30 years. Causes of death mainly include respiratory failure, heart failure, post-traumatic organ failure, surgical complications, as well as a heart attack.

Fig.1 Synthesis and degradation of heparan sulfate (HS). (Benetó, 2020)

Animal Models of Sanfilippo Syndrome

Our established MPS IIIA mouse models contain a spontaneous SGSH mutation, which causes loss of N-sulfoglucosamine sulfohydrolase activity. Patients with Sanfilippo Syndrome type B always lose their walking ability. The developed MPS IIIB mouse models recreate the main characteristics and indicate a potential use for therapeutic approaches. In summary, our animal model can be used to study underlying mechanisms and analyze potential therapies

Fig.2 Potential therapeutic approaches to treat Sanfilippo syndrome. (Benetó, 2020)

Therapeutic Approaches of Sanfilippo Syndrome

Currently, there are no treatments that effectively slow or reverse neurodegeneration in patients with Sanfilippo syndrome. Existing strategies can only alleviate its symptoms.

• Enzyme Replacement Therapy (ERT)

ERT is the most successful strategy that has been approved. This method relies on the proper transport of lysosomal enzymes labeled with mannose 6-phosphate (M6P) to the lysosome. However, it should be noted that the presence of the blood-brain barrier (BBB) significantly reduces the efficiency of ERT.

• Substrate Reduction Therapy (SRT)

SRT is a valid alternative approach to ERT. This approach can reduce the production of accumulated substrates and maintain a balance between synthesis and degradation.

• Pharmacological Chaperones for Enzyme-Enhancement-Therapy

Chaperones are small-molecule compounds that help proteins fold properly. Amino sugars and imino sugars are the most common pharmacological chaperones used in enzyme-enhancing therapy, and can effectively stabilize mutant enzymes to partially restore enzyme activity. Several tested compounds exhibit potential as pharmacological partners against Sanfilippo syndrome.

• Stem Cell Therapy

Stem cell therapy that delivers the correct form of enzymes into the brain has never treated neurological disorders. With the development of iPSC technology, the use of glial precursor cells (GPCs) derived from pluripotent stem cells has emerged as another potential therapy for the treatment.

• Gene Therapy

Gene therapy is the most promising treatment option, delivering the correct gene copy to affected cells to restore enzyme activity. Gene therapy using retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAV) as viral vectors has shown promising efficacy against Sanfilippo syndrome.

Services for Sanfilippo Syndrome

• In Vitro Services
• In Vivo Services
• Ex Vivo Services
• Discovery Services
• Development Services

Sanfilippo Syndrome Drug Discovery Service

Equipped with world-leading platforms and extensive experience, Creative Biolabs provides one-stop drug discovery service for our clients. From the basic target identification to the final IND-enabling, we can meet all the needs of customers.

Creative Biolabs is a leading service provider that focuses on neuroscience research. We can assist you in designing the best research outline customized to meet the requirements of clients' programs. If you are interested in our services and products, please do not hesitate to contact us for more details.

Reference

1. Benetó, N.; et al. Sanfilippo syndrome: molecular basis, disease models and therapeutic approaches. International journal of molecular sciences. 2020, 21(21): 7819.