Schwannomatosis
Schwannomatosis (SWN), also called neurofibromatosis type III, is an uncommon genetic disorder characterized by the growth of multiple non-intradermal schwannomas, usually accompanied by neurological symptoms, particularly chronic pain. As a leading provider of rare disease drug and therapy development services, our company is dedicated to advancing research and innovation in the field of schwannomatosis. We are committed to developing effective drugs and therapies that address the unique challenges posed by this condition.
Introduction to Schwannomatosis
Schwannomatosis is a rare form of neurofibromatosis with an estimated incidence of 1 in 40,000 individuals. The disease typically manifests in early adulthood and is typically associated with a phenotype of chronic pain, numbness, tingling, and weakness. Unlike other forms of neurofibromatosis, schwannomatosis is characterized by the development of multiple non-intradermal schwannomas, primarily located in peripheral nerves but may also involve cranial and spinal nerves. Meningiomas can also occur in some cases but are less common.
Fig.1 NF1/SWN symptom presentation. (Staedtke, Verena, et al., 2023)Pathogenesis of Schwannomatosis
The pathogenesis of schwannomatosis involves genetic and molecular alterations. The majority of cases are associated with mutations in two genes: SMARCB1 and LZTR1.
- Germline mutations in SMARCB1 account for approximately 85% of familial cases and up to 40% of sporadic cases. However, additional somatic mutations are required to trigger the development of schwannomas. Notably, mutations in SMARCB1 can also predispose individuals to atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system.
- Mutations in LZTR1 have also been implicated in Schwannomatosis, particularly in humans without SMARCB1 mutations. Additionally, other genetic alterations, such as inactivating mutations in the NF2 gene and the loss of one copy of chromosome 22, may be present in some cases.
Fig.2 Molecular pathogenesis of schwannomatosis. (Tamura, Ryota., 2021)Targeted Therapy Development for Schwannomatosis
- SMARCB1: As the most commonly mutated gene in Schwannomatosis, targeting SMARCB1 and its associated pathways could hold promise for developing novel therapies.
- LZTR1: Mutations in LZTR1 have been identified in a subset of Schwannomatosis cases, making it an attractive target for therapeutic intervention.
- Histone deacetylase 4 (HDAC4): Interactions between SMARCB1, LZTR1, and HDAC4 have been suggested, and targeting HDAC4 with histone deacetylase inhibitors shows potential as an antitumor strategy.
Our Services
With extensive experience in the development of drugs and therapies for schwannomatosis, our expert teams utilize their vast knowledge and expertise to identify and validate potential therapeutic targets in schwannomatosis. By thoroughly understanding the disease biology and molecular mechanisms, we can prioritize the most promising targets for diagnostics and drug development.
Our SWN Therapy Development Platforms:
Creating dependable animal models is essential for conducting preclinical studies and evaluating the effectiveness of potential therapies. Our company specializes in providing animal model development services tailored specifically for schwannomatosis research. Leveraging advanced genetic engineering techniques, we can introduce precise mutations associated with Schwannomatosis into mice or other suitable animal models. These models enable us to investigate disease progression, assess drug safety, and perform pharmacokinetic analyses for schwannomatosis drugs.
Animal Models of SWN
- SMARCB1 mutation models
- COQ6 mutation models
- LZTR1 mutation models
- NF2 mutation models
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Staedtke, Verena, et al. "Gene-targeted therapy for neurofibromatosis and schwannomatosis: The path to clinical trials." Clinical Trials (2023): 17407745231207970.
- Tamura, Ryota. "Current understanding of neurofibromatosis type 1, 2, and schwannomatosis." International journal of molecular sciences 22.11 (2021): 5850.
- Blakeley, Jaishri O., and Scott R. Plotkin. "Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis." Neuro-oncology 18.5 (2016): 624-638.
- Sanchez, Lauren D., Ashley Bui, and Laura J. Klesse. "Targeted therapies for the neurofibromatoses." Cancers 13.23 (2021): 6032.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.