Neurofibroma Drug Discovery Service

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease with tumor predisposition syndrome. It is a multisystem disorder characterized by complex and multicellular benign but disfiguring neurofibroma tumors. There exist currently no effective therapeutics for NF1. Therefore, it is urgent to find out the molecular mechanisms in the pathogenesis of neurofibroma. Creative Biolabs has more than ten years of experience providing comprehensive solutions in the field of life science. With industry-leading expertise and advanced technologies, our scientists in neuroscience have collected resources worldwide to provide a platform for researchers and developers to investigate the pathogenesis of neurofibroma and thus discover novel effective treatment regimens.

Mechanism of Action Studies of Neurofibroma

Multiple neurofibromas are benign with peripheral nerve sheath tumors accompanied by the onset of NF1, caused by bi-allelic inactivation of the NF1 gene in a subpopulation of Schwann cells (SCs). The neurofibromas are composed of different cells, including SCs, mast cells, macrophages, and fibroblasts intrinsic to the peripheral nerve. Mast cells release transforming growth factor beta (TGF-β), heparin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), which enhance the progression of neurofibroma through tumor angiogenesis and invasiveness. SCs secrete colony-stimulating factors that recruit macrophages to induce inflammation and aggravate neurofibroma.

Fig.1 Plexiform neurofibromas in NF1. (Walker, 2018)

RAS protein is involved in signaling control via the RAS signaling pathway, which regulates multiple cellular processes such as cell growth and differentiation. It has been indicated that the RAS signaling pathway is intimately related to the pathogenesis of NF1. The neurofibromin is encoded by the NF1 gene, participating in the activation of RAS-GTPase and inhibition of RAS activity, which is also known as RAS Activating Protein (RAS-GAP). As a consequence, the deficiency of neurofibromin enhances prolonged activation of downstream RAS-MEK–ERK and PI3K/AKT signaling pathways that are related to cell proliferation and survival.

Fig.2 Neurofibromin is a negative regulator of the RAS signaling pathway. (Walker, 2018)

Neurofibroma Solutions at Creative Biolabs

Understanding the mechanisms of action involved in NF1 enables researchers to develop potential treatments. Creative Biolabs is committed to assisting researchers to develop corresponding gene therapies to restore neurofibromin function. In addition, inhibiting RAS signaling or targeting RAS effectors such as MEK and mammalian target of rapamycin (mTOR) could also be an effective strategy. We offer comprehensive discovery services to explore promising targets for neurofibroma. Besides small molecular agents, we also help researchers to develop immunotherapy, such as anti-PD-, which is also a prospective therapeutic in neurofibroma. Creative Biolabs has a long-term dedication to providing one-stop solutions for neurofibroma studies. We have a variety of in vitro, in vivo, and ex vivo assays with reliable technologies and research platforms that can meet your research and development requirements. The scheme below illustrates our platform and one-stop solution for translational research and integrated research in neurofibroma.

If you have the intention to learn more about preclinical neurofibroma drug discovery solutions, please feel free to contact us.

Reference

1. Walker, J. A.; Upadhyaya, M. Emerging therapeutic targets for neurofibromatosis type 1. Expert opinion on therapeutic targets. 2018, 22(5): 419-437.