Mucopolysaccharidosis Drug Discovery Service

With our commitment to "Global Neurological Expertise", Creative Biolabs endeavors to offer the highest quality and value of one-stop research services in the neuroscience field worldwide to support our clients.

Mucopolysaccharidosis Overview

Mucopolysaccharidosis (MPS) is a group of lysosomal storage diseases (LSDs) arising from deficiencies in enzymatic glycosaminoglycan (GAG) catabolism and can be classified into seven main diseases, which are caused by deficiencies in one of eleven different enzymes, including MPS I, MPS II, MPS III, MPS IV, MPS VI, MPS VII, and MPS IX. Accumulation of partially-degraded GAGs progressively affects multiple organ systems and, possibly together with a cascade of secondary events, produces the classic phenotypes seen in these disorders.

Creative Biolabs' Animal Models of LSDs

Mice and other small laboratory animals will continue to be a very valuable source of disease models and have the advantage of being used in well-characterized inbred lines. For initial studies of pathogenesis and therapy, these naturally occurring LSDs and knockout mouse models have proven extremely valuable. Perhaps due to the often progressive nature and striking clinical signs of LSDs, domesticated animals have been a rich source of models of these diseases.

Creative Biolabs' Mechanism of Action (MoA) Studies of MPS Pathophysiology

The pathophysiological mechanisms of these diseases have been investigated, suggesting impaired autophagy at the initiation of neuronal injury, the association of activated microglia and astrocytes with neuroinflammatory processes, and the involvement of tauopathy.

• Impaired Autophagy and the Role of Microglia in MPS

Studies have shown that impaired autophagy acts as a promoter of neuronal injury, and lysosomes stored in MPS may inhibit autophagose-lysosome fusion. Suppressed and impaired autophagy in MPS would likely provide cellular stress, damage, and death. Recently, FGF signaling degeneration was reported to be associated with early developmental skeletal defects in the MPS II model, suggesting a new venue to discover possible druggable novel key targets in MPSII.

• Tauopathy in MPS

In MPS IIIB model mice, p-tau protein accumulation in the medial entorhinal cortex and coexpression of lysozyme protein in the same neurons have been reported, suggesting that MPS IIIB presents tauopathy similar to the pathology of AD.

• MPS-plus Syndrome (MPSPS)

Fig.1 Impaired autophagy, increased polyubiquitination, and dysfunctional mitochondria in human MPS VI fibroblasts. (Tessitore, 2009)

Therapeutic Approaches

• Enzyme Replacement Therapy (ERT)

There are two insurance-approved therapies for MPS, ERT and hematopoietic stem cell transplantation (HSCT). ERT is currently considered the standard therapy for MPS I, II, IVA, and VI.

• Hematopoietic Stem Cell Transplantation (HSCT)

Allogeneic HSCT has been applied to treat the Inherited Error of Metabolism (IEM) associated with LSD. HSCT is regarded as the standard option for young patients with MPS IH, and Hurler syndrome.

• Gene Therapy

In viral vector-mediated gene therapy, two significant ways for transduction are: in vivo, mainly using an Adeno-associated viral vector (AAV); and ex-vivo, mainly using a lentiviral vector.

• Substrate Reduction Therapy (SRT)

SRT therapy for MPS has been recognized as an alternative therapy for reducing GAG synthesis to correct the imbalance between GAG formation and breakdown.

Creative Biolabs' Services for MPS Preclinical Drug Discovery

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

At Creative Biolabs, we have the expertise to optimize each stage to ensure you get the results you want and achieve the highest level of efficiency. Our expertise is completed by a team of strategic consultants and technical advisors among the most renowned experts in their fields. If you are interested in our Mucopolysaccharidosis research services, please feel free to contact us for more.

Reference

1. Tessitore, A.; et al. Abnormal autophagy, ubiquitination, inflammation, and apoptosis are dependent upon lysosomal storage and are useful biomarkers of mucopolysaccharidosis VI. Pathogenetics. 2009, 2 (1): 1-12.