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Diffuse Intrinsic Pontine Glioma (DIPG)

Diffuse intrinsic pontine glioma (DIPG) is characterized by its diffuse infiltration throughout the pons, making surgical resection impossible. The prognosis for DIPG remains extremely poor, with a median survival of less than one year from diagnosis. Our company specializes in the development of drugs and therapies specifically targeting diffuse intrinsic pontine glioma (DIPG).

Definition of DIPG

Diffuse intrinsic pontine glioma (DIPG), also known as diffuse midline glioma, is a rare and extremely aggressive brain tumor primarily observed in children. The incidence of DIPG is 1 to 2 cases per 100 000 population. It originates in the pons, a critical region of the brainstem responsible for essential functions such as respiratory control, blood pressure regulation, and coordination.

Pathogenesis of DIPG

The pathogenesis of DIPG is complex and involves various genetic and epigenetic alterations. One of the most common genetic mutations found in DIPG is a point mutation in the histone H3 gene, primarily affecting the lysine 27 residue (H3K27M). This mutation leads to global chromatin structure and gene expression changes, contributing to tumor initiation and progression.

Epigenetic alterations, including DNA methylation and modifications of histones, are also key contributors to the development of Diffuse Intrinsic Pontine Glioma (DIPG). DIPG tumors exhibit abnormal DNA methylation patterns, which impact crucial regulatory regions of the genome. Additionally, the dysregulation of histone methyltransferases and demethylases disrupts the normal structure of chromatin, resulting in modified gene expression profiles.

Therapeutics Development of DIPG

• Targets of DIPG Therapy Development
  Developing effective therapies for DIPG relies on identifying specific targets within the tumor cells. The genetic and epigenetic alterations observed in DIPG provide potential targets for therapeutic intervention. One of the most promising targets in DIPG is the H3K27M mutation itself. Strategies aimed at directly inhibiting the activity of mutant histones or modulating downstream pathways affected by the mutation are under investigation. Additionally, other genetic alterations, such as the activation of receptor tyrosine kinase pathways, provide opportunities for targeted therapies.
• Types of DIPG Therapy Development

  Targeted Therapies

  Targeted therapies, focusing on specific molecular alterations, have shown promise in preclinical studies and early-phase clinical trials. For example, a study by Monje et al. (2017) identified a potential target, platelet-derived growth factor receptor alpha (PDGFRA), in DIPG. They demonstrated that inhibiting PDGFRA signaling reduced tumor growth in preclinical models.

  Epigenetic Therapies

  Epigenetic modifiers, such as histone deacetylase inhibitors and demethylating agents, have shown potential in reversing the aberrant epigenetic marks associated with DIPG. Grasso et al. (2015) conducted a study using a demethylating agent called decitabine in DIPG. They observed a partial response in one and stabilization of disease in two, suggesting the potential of epigenetic modifiers in DIPG therapy.

  Immunotherapies

  Investigations are currently underway to explore immunotherapeutic approaches, including CAR T-cell therapy, in order to leverage the immune system's capacity to selectively target and eliminate tumor cells.  A study by Ahmed et al. (2017) explored the use of CAR T-cell therapy targeting the GD2 antigen in preclinical models of DIPG. They observed efficient tumor targeting and regression, indicating the potential of immunotherapies in DIPG therapy.

Our Services

Our company boasts cutting-edge facilities, allowing us to deliver exceptional services in the development of diagnostics and therapies for diffuse intrinsic pontine glioma (DIPG). We offer comprehensive support throughout the entire research continuum. From initial planning and design to experiment execution and data analysis, our team is committed to assisting at every stage. We prioritize timely communication, progress updates, and expert guidance to ensure the success of your project.

Our DIPG therapy development platforms:

With a complete animal model development platform, we provide researchers with reliable and biologically representative DIPG models. These models accurately mimic the characteristics of human DIPG tumors, enabling researchers to study disease mechanisms and evaluate potential therapies with confidence, including pharmacokinetics studies and drug safety evaluation.

Animal Models of DIPG

Why Choose Us?

By working closely with you and understanding your specific research goals, we strive to deliver results that drive scientific progress and contribute to the development of effective therapies for DIPG. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

• Damodharan, S., et al. "Diffuse intrinsic pontine glioma: molecular landscape, evolving treatment strategies and emerging clinical trials." Journal of Personalized Medicine 12.5 (2022): 840. 

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

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