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Medulloblastoma (MDB)

MDB, or Medulloblastoma, is a malignant brain tumor that predominantly affects children. It manifests as the abnormal proliferation of cells in the cerebellum, a region responsible for motor coordination and balance. This condition often leads to increased intracranial pressure and cerebellar dysfunction, resulting in a range of symptoms including headaches, nausea, vomiting, dizziness, and difficulties with mobility. As a prominent provider of drug and therapy development services, our company is dedicated to advancing the field of MDB research. We offer comprehensive and tailored services, along with professional technical support.

Overview of Medulloblastoma (MDB)

Medulloblastoma is rare, occurring in less than 1% of adult central nervous system (CNS) tumors. The exact cause of MDB remains unclear, but studies have identified genetic and molecular alterations that contribute to its development. Advances in molecular profiling have led to the classification of MDB into four subgroups: Hedgehog (Hh) or Sonic hedgehog (Shh), Wnt, Group 3 (Grp3), and Group 4 (Grp4). Each subgroup has distinct genetic and molecular characteristics, influencing the choice of therapeutic targets.

MDB arises from the dysregulation of multiple signaling pathways and genetic alterations:

• The Wnt subgroup is characterized by dysregulated Wnt signaling, primarily caused by somatic activating mutations in the CTNNB1 gene.
• The Hh subgroup involves aberrant activation of the Hedgehog pathway, primarily through mutations in the Patched (Ptch) and Smoothened (Smo) genes.
• Grp3 and Grp4 subgroups have different molecular causes that are yet to be fully characterized.

Targeted Therapy Development for Medulloblastoma (MDB)

• Wnt Targeted Therapy
  The dysregulation of the Wnt signaling pathway in MDB presents therapeutic intervention opportunities. Wnt-targeted therapy can be used as a potential drug development option for MDB by inhibiting abnormal Wnt signaling. Inhibiting β-catenin, encoded by the CTNNB1 gene, has shown promising results in preclinical models.
• Hedgehog (Hh) Targeted Therapy
  The Hh pathway plays a critical role in MDB pathogenesis, particularly in the Hh subgroup. Targeting this pathway using Hh pathway inhibitors has shown therapeutic potential. Small molecule inhibitors of Ptch and Smo, key components of the Hh pathway, have been evaluated in preclinical and clinical trials.
• PDE4D Targeted Therapy
  Recent studies have implicated mutations in the PDE4D gene in adult Hh-MB, suggesting PDE4D as a potential therapeutic target. Inhibition of PDE4D has shown promising results in inhibiting the growth of Hh-MB.
  In addition, there are other potential targets for the development of MDB drugs and therapies:
  
  • HDAC
  • BET-bromodomain
  • LSD1
  • FACT
  • PI3K/AKT/mTOR

  • CDK
  • CK2
  • CHK1 kinase
  • ROCK
  • WEE1 kinase

  • Src kinase
  • PDE4D
  • DDX3
  • PARP
  • Sp1

  • HMGCR
  • ABC transporter
  • COX-2
  • mGPD

Our Services

With a comprehensive technology platform and a top-of-the-line team, our company provides MDB diagnostic and therapy development services. Combining therapies aims to enhance efficacy and overcome drug resistance by simultaneously targeting different pathways or mechanisms. Our company is committed to the development of combination therapy services, to provide more possibilities for your MDB research.

Our MDB therapy development platforms:

Our preclinical evaluation services include cell-based assays, animal model studies, drug safety evaluation, and pharmacokinetic profiling. These comprehensive evaluations enable us to select the most promising drug candidates for further development.

Animal Models of MDB

If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

• Wen J., and Hadden, M. K., "Medulloblastoma drugs in development: Current leads, trials, and drawbacks." European journal of medicinal chemistry 215 (2021): 113268.
• Cambruzzi, Eduardo. "Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation." Child's Nervous System 34 (2018): 809-815.
• Wang, Qiyue, et al. "Medulloblastoma targeted therapy: from signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies." Pharmacology & Therapeutics (2023): 108527.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

• Glioblastoma (GBM)
• Diffuse Intrinsic Pontine Glioma (DIPG)