Severe Congenital Neutropenia (SCN)
Severe congenital neutropenia (SCN) is a group of rare diseases that affect bone marrow production. With our groundbreaking advancements in SCN research, we lead the way in developing state-of-the-art diagnostic tools and therapeutics to enhance the efficient management of SCN. As your dependable collaborator in SCN research, we provide unparalleled assistance to meet your scientific research requirements.
Overview of Severe Congenital Neutropenia
Severe congenital neutropenia (SCN) refers to a collection of uncommon genetic disorders marked by abnormally reduced levels of neutrophils, a vital type of white blood cell that plays a crucial role in defending the body against bacterial and fungal infections. Individuals affected by SCN face a significantly heightened susceptibility to recurrent and severe infections, particularly in the sinuses, lungs, liver, gums, and skin. The incidence of SCN is approximately 3-4 cases per million births.
Fig. 1 Mechanism of severe congenital neutropenia caused by JAGN1 deficiency. (Thomas, Sanya, et al., 2023)Pathogenesis of Severe Congenital Neutropenia
There are multiple subtypes of severe congenital neutropenia (SCN), including SCN1, SCN2, SCN3, SCN4, SCN5, SCNX, etc. Among them, SCN1 is the most common form of SCN, accounting for 60-80% of SCN. These disease subtypes are primarily caused by mutations in multiple genes related to neutrophil development and function.
Table. 1 Common subtypes and inheritance patterns of severe congenital neutropenia
| Disease Subtypes | Mutated Gene | Chromosome | Inheritance |
| SCN1 | ELANE | 19p13.3 | AD |
| SCN2 | GFI1 | 1p22.1 | AD |
| SCN3 | HAX1 | 1q21.3 | AR |
| SCN4 | G6PC3 | 17q21.31 | AR |
| SCN5 | VPS45 | 1q21.2 | AR |
| SCNX | WASP | Xp11.23 | XL |
Therapeutics of Severe Congenital Neutropenia
Therapeutics of severe congenital neutropenia (SCN) mainly includes drug intervention, stem cell transplantation, and gene therapy. These approaches are all designed to address underlying genetic defects or boost the production and function of neutrophils.
Drug Intervention
Granulocyte colony-stimulating factors (G-CSFs), such as filgrastim and lenograstim, have been successfully used to increase neutrophil counts and reduce the frequency of infections in SCN individuals. These drugs act by stimulating the bone marrow to produce more neutrophils and improving their survival.
Stem Cell Transplantation
Hematopoietic stem cell transplantation (HSCT) involves replacing defective hematopoietic stem cells with healthy hematopoietic stem cells from a compatible donor to restore normal neutrophil production and function. This approach requires careful consideration of factors such as donor matching and potential complications.
Gene Therapy
Scientists are exploring strategies such as gene editing using CRISPR-Cas9 technology to precisely modify the defective genes associated with SCN. By correcting the gene mutations, it may be possible to restore normal neutrophil production and function, providing a potential cure for the disorder.
Our Services
As a frontrunner in the field of biological research and CRO services, our company is dedicated to offering holistic solutions for the diagnostics development and therapy research of severe congenital neutropenia. Through collaborations with industry experts, we have established all-encompassing platforms for rare diseases to facilitate severe congenital neutropenia therapy development.
Platforms of Severe Congenital Neutropenia Therapy Development
Recognizing the significance of dependable animal models in severe congenital neutropenia disease research, our company is committed to offering animal model development services that facilitate preclinical research and aid in drug discovery endeavors.
Animal Models of Severe Congenital Neutropenia
| Induced Models | |||
| Inducing mutations in animal models can mimic features of severe congenital neutropenia (SCN). Our scientists use chemical mutagenesis or physical radiation to introduce random mutations in the animal genome, and through careful screening, animals with SCN-like phenotypes can be identified. | |||
| Xenograft Models | |||
| The xenograft model utilizes the transplantation of patient-derived hematopoietic stem cells (HSCs), which carry the genetic defects associated with SCN, into the bone marrow of animal hosts. This procedure transfers the genetic abnormalities observed in human patients to the animal model, resulting in the development of a phenotype that closely resembles SCN. Commonly used cell lines include HL-60, PLB-985, KG-1, etc. | |||
| Genetically Engineered Models | |||
| Our company specializes in developing genetic engineering models of SCN. For example, the ELANE gene encoding neutrophil elastase is frequently mutated in the SCN. Our scientists use advanced genetic manipulation techniques, such as gene knockout or gene knock-in, to introduce ELANE gene mutations in animal models to study their effects on neutrophil production and function. | |||
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| Optional Species | Mice, Zebrafish, Dogs (Collies and Border Collies), Non-human Primates (Monkeys), Others | ||
With complete animal species resources, we can meet your diversified preclinical research including drug safety evaluation and pharmacokinetic analysis. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Thomas, Sanya, et al. "Severe congenital neutropenia due to jagunal homolog 1 (JAGN1) mutation: a case report and literature review." Frontiers in Pediatrics 11 (2023): 1223191.
- Schäffer, Alejandro A., and Christoph Klein. "Animal models of human granulocyte diseases." Hematology/Oncology Clinics 27.1 (2013): 129-148.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.