ENDECE will be attending Bio International Boston from June 4-7, 2018. In our meetings, we will be discussing ENDECE’s recent discovery that predicts NDC-1308 should demonstrate clinical efficacy for inducing remyelination in diseases such as MS, NMO and AD. ENDECE discovered NDC-1308 upregulates lipoprotein lipase (LPL) gene expression in addition to upregulating key genes for inducing OPC differentiation into mature, myelinating oligodendrocytes.
The ability off NDC-1308 to upregulate LPL gene expression is important because Bruce et al (Front Molec Neurosci, 2018, 11: article 57) discovered LPL protein switches macrophages from M1 phenotype (pro-inflammatory and anti-remyelination) to the M2 phenotype (anti-inflammatory and pro-remyelination). Lesions from post-mortem MS patients that have no signs of remyelination contain predominantly M1 macrophages whereas lesions where remyelination is observed contain predominantly M2 macrophages (Front in Cell and Devel Bio, 2016, 4: article 60). M2 macrophages actively phagocytize myelin debris in areas of demyelination (myelin debris is inhibitory to remyelination).
While we confirm NDC-1308 upregulation of LPL gene expression switches the polarization of M1 macrophages to M2 macrophages, ENDECE’s working model for NDC-1308 induction of remyelination is described as:
- up-regulation of LPL gene expression to switch macrophages to the anti-inflammatory, pro-remyelination M2 phenotype and
- up-regulation of key genes to induce OPC differentiation (OLIG2, MBP, MOG, DNER).
NDC-1308 has a desirable safety profile in mice (normal behavior, normal clinical chemistry, not genotoxic, not mutagenic, not estrogenic, and not pro-arrhythmic) and reproducibly induces remyelination in the cuprizone mouse model of demyelination. IND-enabling studies will utilize nasal drug administration followed by Phase 1 studies in patients with neuromyelitis optica (NMO) for early proof-of concept as an orphan drug.
ENDECE is a privately held biotechnology company dedicated to improving the lives of patients suffering from diseases for which treatment options are limited or non-existent. If you plan to attend conference, and would like to meet with ENDECE to discuss the company’s latest developments, please contact Dr. James Yarger at firstname.lastname@example.org.