Neurofibromatosis Type 1 (NF1)
Neurofibromatosis Type 1 (NF1) is a genetic disorder characterized by the growth of tumors on nerves throughout the body, impacting the nervous system. Our company actively seeks collaborations with academic institutions and pharmaceutical companies to offer comprehensive services in the development of drugs and therapies for NF1. By combining the expertise and resources of our partners, we strive to expedite the translation of scientific breakthroughs into effective drug discovery and development.
Introduction to Neurofibromatosis Type 1
Neurofibromatosis Type 1 (NF1), also known as von recklinghausen disease, is an inherited disorder caused by mutations in the NF1 gene, which is located on chromosome 17. NF1 affects approximately 1 in 3,000 individuals worldwide and exhibits a wide range of symptoms. The hallmark feature of NF1 is the development of neurofibromas, benign tumors that grow along nerves in the body. These tumors can cause significant discomfort and functional impairment, particularly when they become large or form plexiform neurofibromas.
Pathogenesis of Neurofibromatosis Type 1
The pathogenesis of NF1 involves dysregulation of the Ras signaling pathway, which plays a crucial role in cell growth and division. The NF1 gene encodes neurofibromin, a protein that acts as a negative regulator of Ras activity. Mutations in the NF1 gene lead to reduced neurofibromin function, resulting in increased Ras signaling and abnormal cell proliferation. The dysregulated Ras signaling pathway contributes to the formation of neurofibromas and other manifestations of NF1, including café-au-lait spots, freckling, skeletal abnormalities, and optic gliomas.
Fig.1 Molecular pathogenesis of NF1. (Tamura, Ryota., 2021)Targets of Neurofibromatosis Type 1 Therapy Development
Targeting the Ras signaling pathway is a key focus of NF1 drug and therapy development. Ras proteins function as molecular switches, relaying signals from cell surface receptors to intracellular signaling pathways. Several downstream effectors of Ras, such as MEK and PI3K, have been identified as potential therapeutic targets.
In addition to targeting the Ras pathway, other potential drug targets in NF1 include bromodomain-containing protein 4 (BRD4), which is upregulated in malignant peripheral nerve sheath tumors (MPNSTs), and immune checkpoint molecules to enhance the anti-tumor immune response.
Types of Neurofibromatosis Type 1 Therapy Development
- Targeted Therapies
Small molecule inhibitors that specifically target components of the Ras signaling pathway, such as MEK inhibitors like selumetinib, have shown promise in controlling tumor growth. These inhibitors disrupt key steps in the pathway, inhibiting abnormal cell proliferation and promoting tumor regression.
- Immunotherapies
Immunotherapeutic strategies have emerged as a promising avenue to exploit the body's immune system for the specific targeting and elimination of tumor cells. Immune checkpoint inhibitors, including those designed to block programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have demonstrated the ability to enhance the immune response against NF1-related tumors.
- Gene Therapies
Gene therapy approaches hold great potential for treating NF1. These strategies involve introducing functional copies of the NF1 gene or utilizing gene editing techniques to correct the mutation in affected cells. Gene therapies are still in the early stages of development but offer a promising avenue for future therapies.
Fig.2 Current therapeutics strategies under development. (Brosseau, J.P., et al., 2020)Our Services
As a leading force in the field of rare disease research, our company offers a diverse range of services dedicated to the diagnostic and therapy development for NF1-related tumors. Employing state-of-the-art techniques, we diligently identify and validate novel targets for drug development in NF1. Our team of experts utilizes cutting-edge genomic, proteomic, and bioinformatic approaches to pinpoint crucial players in the Ras signaling pathway and other potential therapeutic targets.
Featured Platforms
Animal models play a crucial role in preclinical research and the development of effective therapies for NF1. Our company offers exceptional animal model development services for pharmacokinetics studies and drug safety evaluation, including the creation of genetically engineered mouse models (GEMMs) and porcine models of NF1.
NF1 Model Development
- Nf1-/- models
- Nf1+/- models
- Neuronal Nf1 conditional knockout models
- Astrocyte Nf1 conditional knockout models
- Nf1 exon 23a knockout models
- Nf1-/- chimera models
- Nf1+/-: p53+/- models
- Others
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Tamura, Ryota. "Current understanding of neurofibromatosis type 1, 2, and schwannomatosis." International journal of molecular sciences 22.11 (2021): 5850.
- Brosseau, J.P., et al., "Translating current basic research into future therapies for neurofibromatosis type 1." British journal of cancer 123.2 (2020): 178-186.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.