Systemic Mastocytosis (SM)
Systemic mastocytosis (SM), also known as systemic mast cell disease, involves the spread of clonally derived mast cells across various tissues such as bone marrow, skin, gastrointestinal tract, liver, and spleen. Specialized drug and therapy development services are essential to enhance and expedite Systemic Mastocytosis research. Our company is well-equipped to address your drug and therapy development requirements in Systemic Mastocytosis therapy.
Introduction to Systemic Mastocytosis
Systemic Mastocytosis is a rare clonal hematologic disorder marked by the abnormal proliferation and activation of mast cells, which accumulate in various organs such as the skin, bone marrow, and gastrointestinal tract. The disease can range from an indolent condition that many individuals live with for years without progression to a more aggressive form that can lead to organ dysfunction and systemic symptoms.
Due to the rarity of the disease, specific incidence rates are challenging to ascertain, but the number of well-documented cases has risen substantially over the past two decades.
Pathogenesis of Systemic Mastocytosis
The pathogenesis of Systemic Mastocytosis is complex and involves several genetic and molecular factors. A mutation in the KIT gene, particularly the D816V mutation, is central to the development of Systemic Mastocytosis, which is present in over 80% of cases. This mutation leads to the autonomous activation and proliferation of mast cells. Despite being a weak oncogene, the KIT D816V mutation is a critical event in the development and progression of the disease.
Fig.1 Genetic complexity among systemic mastocytosis subtypes. (Reiter, A., et al., 2020)Diagnostics Development of Systemic Mastocytosis
Flow cytometry and molecular genetic testing are crucial tools in diagnosing systemic mastocytosis. Flow cytometry identifies abnormal mast cell populations in bone marrow and blood by assessing altered expression of surface markers like CD25 and CD2, which are characteristic of the disease. Concurrently, molecular genetic testing plays a critical role, especially for the D816V mutation in the KIT gene. This mutation is highly specific to systemic mastocytosis and is detected using PCR and other molecular techniques, enhancing diagnostic precision and facilitating targeted treatment strategies.
Therapy Development of Systemic Mastocytosis
Small molecule inhibitors like midostaurin and avapritinib have been pivotal in the therapy of SM. Midostaurin targets multiple kinases including KIT, FLT3, and PDGFR, and has shown efficacy in reducing the symptoms and progression of SM. Avapritinib, explicitly targeting the KIT D816V mutation prevalent in SM, offers a more focused approach with potentially fewer side effects due to its precision targeting.
Although not as extensively developed for SM as for other diseases, the principles of cell therapies like Chimeric Antigen Receptor T-cells (CAR-T) have shown promise in the broader oncology landscape. These therapies involve engineering individuals' T cells to recognize better and attack cancer cells, a concept that could potentially be adapted to target malignant mast cells in SM in future research.
Monoclonal antibodies, such as omalizumab, have been used to manage symptoms in Systemic Mastocytosis, particularly those related to mast cell activation, such as anaphylaxis and skin manifestations. These antibodies work by targeting and neutralizing specific proteins involved in allergic reactions.
Gene therapy approaches are at a more exploratory stage for SM. The concept involves modifying genes directly to correct the mutations that cause diseases like SM. This could involve techniques like CRISPR/Cas9, which has shown potential in editing genes responsible for other genetic disorders and could be directed at the KIT mutation in Systemic Mastocytosis.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Systemic Mastocytosis therapy strategies and ensure robust support throughout the process.
Platforms of Systemic Mastocytosis Therapy Development
Animal Models of Systemic Mastocytosis
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to Systemic Mastocytosis. These models allow researchers to simulate and study the complex biological processes associated with Systemic Mastocytosis. | ||
| Optional Models |
|
|
| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Systemic Mastocytosis. | ||
| Optional Models |
|
|
| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Reiter, A., et al., "New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis." Blood, (2020). 135(16): p. 1365-1376.
- Li, Z.X., "New Insights into the Pathogenesis of Systemic Mastocytosis." International Journal of Molecular Sciences, (2021). 22(9).
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.