Hypereosinophilic syndrome (HES) is a complex myeloproliferative disorder. At Protheragen, we focus on creating novel therapeutics and building accurate animal models to accelerate preclinical studies of potential therapies for HES. Our expertise ensures that your research receives the most reliable and relevant support, accelerating your drug development journey.
Overview of Hypereosinophilic Syndrome (HES)
Hypereosinophilic syndrome (HES) is a group of rare and complex disorders which is marked by continued and excessive production of eosinophils, a type of white blood cell. Prolonged elevated levels of tissue eosinophils can result in tissue destruction and organ damage, especially to the heart, skin, lungs, gastrointestinal system, and even the nervous system. HES is a myeloproliferative disorder and is subdivided into primary, secondary, and idiopathic forms based on its etiology.
Fig. 1 Classification and characteristics of hypereosinophilic syndrome variants. (Cogan, Elie, and Florence Roufosse., 2012)
Pathogenesis of Hypereosinophilic Syndrome (HES)
The pathobiology of hypereosinophilic syndrome (HES) entails the abnormal production and activation of eosinophils, a class of white blood cell, causing tissue damage and organ dysfunction.
- Primary HES: Genetic mutations such as the FIP1L1-PDGFRA fusion gene drive the constitutive activation of signaling pathways (e.g., PDGFRA, JAK/STAT), promoting eosinophil proliferation and survival.
- Secondary HES: In this condition, high eosinophilia arises from excessive eosinophilic cytokine production (e.g., IL-5) caused by some infection, allergy, or autoimmune disease.
- Idiopathic HES: This mechanism of HES is not well understood, but it seems to follow the patterns of eosinophil overactivity. Eosinophils excrete harmful proteins that lead to inflammation and destruction of organs.
Therapy Development for Hypereosinophilic Syndrome (HES)
The available treatments for hypereosinophilic syndrome (HES) are hyper specialized, including corticosteroids, immunosuppressants, and monoclonal antibody therapies that focus on the activation and overproduction of eosinophils. The identification of genetic drivers such as the FIP1L1-PDGFRA fusion gene has opened new avenues for precision medicine, including the use of tyrosine kinase inhibitors (TKIs) such as imatinib.
Table. 1 Drug development pipeline for hypereosinophilic syndrome (HES).
| Drugs |
Types |
Targeted |
Developmental Stage |
| Mepolizumab |
Monoclonal antibody |
IL-5 |
Approved |
| Benralizumab |
Monoclonal antibody |
IL-5Rα |
Approved |
| Imatinib |
Tyrosine kinase inhibitor (TKI) |
PDGFRA, ABL, KIT |
Approved |
| Nilotinib |
Tyrosine kinase inhibitor (TKI) |
PDGFRA, ABL, KIT |
Approved |
| Lirentelimab |
Monoclonal antibody |
Siglec-8 |
Phase II |
| Deucravacitinib |
JAK inhibitor |
JAK1, JAK2 |
Approved |
| Dexpramipexole |
Eosinophil-depleting agent |
Eosinophil maturation |
Phase III |
| Ruxolitinib |
JAK1/JAK2 inhibitor |
JAK/STAT pathway |
Approved |
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
Protheragen is dedicated to providing unmatched diagnostic and therapeutic development services for hypereosinophilic syndrome (HES). We also have unique expertise in developing advanced disease models that enable preclinical investigations for therapy. We apply innovation and accuracy to equip our clients with solutions that foster efficacious intervention strategies.
Services We Offer
Animal Model Development
- FIP1L1-PDGFRA Knock-in Models
- IL-5 Transgenic Models
- Siglec-8 Knock-out Models
- Tamoxifen-Inducible FIP1L1-PDGFRA Models
- Patient-Derived Xenograft (PDX) Models
- Cell Line-Derived Xenograft Models
At Protheragen, we are committed to supporting the development of innovative therapeutics through comprehensive preclinical research services, including pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies. Our customized approach addresses the unique challenges of your studies and helps you optimize your drug candidates for commercial success. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Cogan, Elie, and Florence Roufosse. "Clinical management of the hypereosinophilic syndromes." Expert review of hematology 5.3 (2012): 275-290.
