Systemic Mastocytosis (SM)
Systemic mastocytosis (SM), or systemic mast cell disease, is characterized by the distribution of clonally derived mast cells over the bone marrow, skin, gastrointestinal tract, liver and spleen. In order to further and accelerate Systemic Mastocytosis research, specialized drug and therapy development services are needed. As such, we stand ready to meet your specific Systemic Mastocytosis therapy drug and therapy development needs.
Introduction to Systemic Mastocytosis
Systemic Mastocytosis is an exceedingly uncommon hematological disorder that is derived from a single cell. It is characterized by uncontrolled growth and activation of mast cells in multiple body systems which include skin, bone marrow, and the gastrointestinal tract. This condition may present as an indolent disease, which is the most common type, often causing no symptoms for many years, or as an aggressive form resulting in organ dysfunction and other severe symptoms.
Incidence rates can be difficult to determine due to the rarity of the disease, however, the documented cases over the last 20 years have seen a notable increase.
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 affects several molecular and genetic components, making it difficult to clarify. The D816V mutation in the KIT gene is particularly important and is found in more than 80% of Systemic Mastocytoses. This particular mutation causes mast cells to undergo uncontrolled activation and multiplication. The KIT D816V mutation, despite its status as a weak oncogene, is fundamental to the onset and advancement of the disorder.
Fig.1 Genetic complexity among systemic mastocytosis subtypes. (Reiter, A., et al., 2020)Diagnostics Development of Systemic Mastocytosis
Diagnosis of these systemic diseases relies on molecular markers, in a case of ST from the KIT gene or any other mutations associated with it. Flow cytometry detects neoplastic abnormalities of mast cells within blood and bone marrow by checking for surface markers characteristic of the disease such as CD25 and CD2. At the same time, the molecular genetic testing for the D816V mutation in the KIT gene is performed. This locus is one of the most, if not the most, distinguishing factors for systemic mastocytosis and is reached with a PCR and other methods of molecular biology. This improves accuracy in diagnosis and allows for more precise treatment options to be utilized.
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.
Compared to other conditions, SM is yet to fully realize the concept of cell therapies. However, there have been promising trends with Chimeric Antigen Receptor T-cells (CAR-T) which could potentially be used against mast cell malignancies of these patients. These treatments involve modifying T cells from the patient so they can better identify and attack the cancer, and this may be less difficult to accomplish for malignant mast cells.
Monoclonal therapeutic antibodies like omalizumab have been used to treat symptomatology following System Mastocytosis particularly those induced by mast cell components such as anaphylactic shock and dermatographism. Such antibodies are able to inhibit some of the specific proteins responsible for allergic responses.
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.
With respect to SM, gene therapy approaches are at a much more advanced stage. The idea is to attempt to directly retouch a gene which is expected to rectify the mutations that cause diseases such as SM. This might include the use of gene editing technologies which has been used to edit the genes for other genetic disorders and might be targeted towards the KIT mutation in Systemic Mastocytosis.
Our Services
We have expertise within the company as well as external collaborators. This enables us to work together with the clients in creating innovative and customized Systemic Mastocytosis therapy solutions while ensuring adequate support throughout the entire effort.
Platforms of Systemic Mastocytosis Therapy Development
Animal Models of Systemic Mastocytosis
We possess developed and validated animal models that closely replicate the salient features of the disease as well as the responses to therapy. These models make it possible to assess the safety and efficacy of 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. | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Systemic Mastocytosis. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services are designed to accommodate other models which focus on signaling pathways and molecular targets of interest.
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.