Study Shows Potential of Novel Compound to Treat Multiple Sclerosis

Mouse model
Mouse model
Investigational agent has the potential to repair damaged myelin sheath and restore function in patients with secondary-progressive multiple sclerosis.

VANCOUVER, British Columbia — For the treatment of secondary-progressive multiple sclerosis (SPMS), NDC-1308−a small molecule that activates intracellular pathways for oligodendrocyte progenitor cell (OPC) differentiation−showed favorable pharmacokinetic properties and was safe in a mice study.

“NDC-1308 possesses many desirable qualities for a therapeutic to treat [multiple sclerosis (MS)],” said study researcher Steven H. Nye, PhD, who is vice-president of discovery at ENDECE (Mequon, Wisconsin). “In particular, it … readily traverses the blood-brain barrier where it can induce OPCs in the [central nervous system (CNS)] to differentiate into cells that synthesize and maintain the myelin sheath, in a similar manner thought to occur in healthy individuals.”

The findings were presented at the 2006 annual meeting of the American Academy of Neurology (AAN).

According to Dr Nye, the catalyst for the study was the current lack of approved therapies for SPMS that repair damaged myelin sheath and potentially restore some level of function to these patients.

“NDC-1308 stimulates oligodendrogenesis, which is a normal physiological process taking place in our body whereby OPCs become mature, myelinating oligodendrocytes,” he said. “The OPCs are known to reside in the CNS of SPMS patients and patients with other forms of MS, but are believed to be ‘stalled’ at the spots where there is myelin damage. We believe NDC-1308 will enhance CNS remyelination in MS patients, thereby leading to repair of the damaged myelin sheaths, to some degree.”

To better understand the safety and efficacy of NDC-1308, Dr Nye and James Yarger, PhD, chief executive officer of ENDECE, undertook a study in which mice were treated with cuprizone/rapamycin to cause demyelination of brain regions, and then administered NDC-1308 for up to 6 weeks.

At week 3, researchers assessed animal grip strength, and at termination they evaluated brain regions to assess the level of NDC-1308 remyelination.

Results demonstrated that NDC-1308 rapidly crossed the blood-brain barrier and was absorbed into CNS tissues at levels that surpassed the EC50 required for OPC differentiation in vitro. At 24 hours, NDC-1308 was eliminated from the CNS and periphery.

After demyelinated mice received chronic NDC-1308 treatment, remyelination increased 18% (P<.01) in cortical regions and 44% (P<.0001) in hippocampal regions.

Researchers also reported significant increases in grip strength with NDC-1308, normal clinical chemistries and animal behavior, and that the OPC population remained intact. They also observed that NDC-1308 was nonmutagenic and nongenotoxic.

“We conclude that NDC-1308 is a potent remyelinating agent with great therapeutic potential for treating MS patients,” Dr Nye said. “NDC-1308 displays favorable pharmacokinetic properties, and it appears to be safe as it is metabolized and eliminated in the periphery. On the other hand, it remains intact and active within the CNS tissues where it is needed to function. In addition, NDC-1308 is not genotoxic or mutagenic, adding to the safety profile.”

Dr Nye added that because of the compound’s unique mechanism of action, it has the potential for use as monotherapy or in combination with current MS drugs.

“Next steps are to complete [investigational new drug (IND)]-enabling studies (large animal safety/toxicology studies), file the IND, and proceed with a phase 1 first-in-man study,” he said.

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


Nye SH, Yarger J. NDC-1308, a small molecule with remyelinating activity for treatment of secondary progressive multiple sclerosis patients. Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia, Canada. Abstract I10.007