New Data Demonstrate Gain of Function Without Side-Effects Associated with Estrogens
ENDECE Neural announced the forthcoming presentation of new evidence that the company’s lead compound, NDC-1308, an analog of estradiol being investigated for the treatment of multiple sclerosis (MS), has gained the function to remyelinate damaged axons in animal models, but does not appear to cause the deleterious side effects commonly associated with estrogens. James G. Yarger, Ph.D., ENDECE CEO, presented these results at the BioPharm America conference to be held in Boston, Mass. from September 15-17, 2015.
Presentation Title: “Remyelination Therapy for Progressive Multiple Sclerosis Patients”
Date and Time: Wednesday, September 16, 2015, 12:00 PM EDT
Location: Boston Marriott Copley Place, Suffolk Room, Level 3
NDC-1308 was previously shown in culture to cause 3-fold more mouse oligodendrocyte progenitor cells (OPCs) to differentiate into mature myelinating oligodendrocytes, compared to vehicle. Estradiol and estriol do not possess this myelinating activity. In addition, side-by-side comparison of NDC-1308 and estradiol in the cuprizone mouse model of demyelination showed that only NDC-1308 can induce a significant level of remyelination (up to 44% in the hippocampus). Together, these results clearly distinguish the remyelinating efficacy of NDC-1308 from other estrogens.
To alleviate potential safety concerns for long-term treatment in patients with MS, NDC-1308 was next tested for estrogenicity using a standard mouse uterotrophic assay. In a side-by-side comparison with estradiol, NDC-1308 was found not to be estrogenic. Further testing revealed that NDC-1308 is not mutagenic and not genotoxic.
“These findings are encouraging because NDC-1308 is an estrogen receptor agonist, like estradiol, but elicits a vastly different biological response that ultimately makes it an efficacious and safe remyelinating therapeutic,” commented Dr. Yarger. “Its unique mechanism of action and its demonstrated potent remyelinating activity make NDC-1308 a promising therapeutic candidate for multiple sclerosis. We therefore plan to conduct formal large animal toxicology studies of NDC-1308 followed by a Phase 1 clinical trial in patients with MS.”
NDC-1308 is a novel chemical entity designed to address the damage to the myelin sheath that occurs in patients with secondary progressive MS (SPMS), a common later phase of the disease that follows relapsing-remitting MS (RRMS). NDC-1308 is being developed for potential use either alone or in combination with other MS therapeutics that slow the progression of the disease. By dramatically up-regulating key genes in pathways leading to oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis, NDC-1308 appears to induce restoration of the lost myelin sheath that is believed to cause the devastating symptoms of MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier, allowing it to reach the tissues in the brain and spinal cord where promoting myelin production is needed. NDC-1308 works by inducing differentiation of OPCs into mature oligodendrocytes, cells that synthesize and maintain the myelin sheath. ENDECE Neural discovered NDC-1308, and owns the intellectual property surrounding the compound.