INFIXION’S SCIENTIFIC APPROACH
Neurofibromin is Key
Understanding neurofibromin, the protein produced by the NF1 gene, is key to iNFixion Bioscience’s approach to treating NF1. Decades of research have shown that neurofibromin regulates critical biological pathways across various cell types, including neurons, peripheral nerves, and immune cells.
It plays a vital role in controlling cell growth (Ras/MEK, mTOR pathways), memory and pain processing (dopamine/cAMP/HCN channels), and the development of the brain, bones, cardiovascular system, and skin.
While its full function is still being studied by researchers across the world, neurofibromin’s widespread regulatory role explains the diverse symptoms seen when it is mutated or missing in people living with NF1.
Two Key Principles
Autosomal Dominance & Haploinsufficiency
There are two key genetic principles at the center of understanding how iNFixion Bioscience proposes to treat NF1.
1) Autosomal Dominance: NF1 is classified as an ‘autosomal dominant’ genetic disorder. Autosomal dominance simply means that a mutation (whether inherited from a parent or caused by a spontaneous mutation at conception) exists on just one of the two copies (alleles) of the NF1 gene, but that this ‘single-sided mutation’ is sufficient to cause symptoms to manifest, even though the other copy of the NF1 gene is completely normal. People with an NF1 mutation therefore produce about 50% fully-functional neurofibromin from the normal gene copy, and 50% non-functional (or partially functional) neurofibromin from the mutated copy of the NF1 gene.
2) Haploinsufficiency: Publications have also shown that many (if not all) of the NF1 symptoms are directly the result of (or made much worse by) neurofibromin haploinsufficiency. Haploinsufficiency simply means that it is the insufficient quantity of normal neurofibromin, and not the mutated protein itself, that is the primary mechanism causing NF1 manifestations. The importance of haploinsufficiency in NF1 symptom progression has been demonstrated in a wide range of primary research, a summary of which is now available from iNFfixion.
Together, autosomal dominance and haploinsufficiency provide the scientific basis for iNFixion Bioscience’s unique approach to treat NF1.
THE INFIXION BIOSCIENCE APPROACH
Increase Functional Neurofibromin in NF1-Critical Cells
People living with NF1 have insufficient levels of functional neurofibromin protein, driving disease symptoms. Our mission is to develop a therapy that increases neurofibromin levels to prevent, reduce, or eliminate NF1 symptoms.
Restoring neurofibromin has been shown to correct key biological pathways and slow or prevent NF1 symptoms caused by its deficiency. iNFixion Bioscience is developing targeted therapies to help NF1 patients produce and maintain functional neurofibromin protein. Using advanced gene regulation techniques, our approach boosts the body’s natural ability to produce neurofibromin from the non-mutated (normal) copy of the NF1 gene, ultimately restoring normal levels of neurofibromin protein.
iNFixion’s NF1 Haploinsufficiency Correction Therapy (HCT)
For more details on iNFixion Bioscience’s rationale for “NF1 Haploinsufficiency Correction Therapy (NF1-HCT)”, please see our 2022 peer-reviewed publication in the Journal of Translational Genetics and Genomics.
iNFixion Bioscience’s Research & Development Pipeline
iNFixion Bioscience aims to develop safe and effective therapies that address the root cause of NF1 symptoms—NF1 protein (neurofibromin) haploinsufficiency. By restoring NF1 protein levels, this treatment approach has the potential to both manage and prevent a broad spectrum of NF1 manifestations, regardless of the specific NF1 mutation.
