Last updated July 6, 2022, by Teresa Carvalho, MS
ā Fact-checked by InĆŖs Martins, PhD
What is NDC-1308 for MS?
NDC-1308 is an investigational therapy that has been tested in preclinical studies for promoting the repair of myelin, the protective covering around nerve fibers, in multiple sclerosis (MS) and other demyelinating diseases.
Endece Neural, the company developing NDC-1308, announced in early 2017 that it had plans to start testing the medication in clinical trials of healthy volunteers the following year. However, no further updates about this developmental program have been released since.
How does NDC-1308 work?
In MS, the immune system wrongly recognizes myelin, the sheath surrounding nerve fibers, as foreign, and mounts an immune response against it. The resulting myelin damage and loss (demyelination) slows the transmission of electrical impulses along the nerve fibers, and makes nerve cells more vulnerable to degeneration.
In normal circumstances, the damaged myelin can be repaired by oligodendrocytes, the myelin-producing cells of the brain and spinal cord. But the ongoing inflammation in MS renders this repair process largely inefficient.
NDC-1308 is a small molecule that is expected to slow the progression of MS and other demyelinating disorders through a dual mechanism: both reducing inflammation and boosting myelin repair.
The compound is similar to the estradiol molecule, the most common form of estrogen, and is therefore able to activate a number of genes by binding to the estrogen receptor. However, estradiol and NDC-1308 have distinct effects on cells.
Specifically, NDC-1308 promotes the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, without the side effects that are normally associated with estradiol.
The genes affected by the investigational treatment also cause macrophages, specific cells of the immune system, toĀ acquireĀ anti-inflammatory properties. These anti-inflammatory cells produce signaling molecules that help dampen the activity of other immune cells, and that promote tissue repair.
Also, NDC-1308 is able to effectively cross the blood-brain barrier, a membrane that protects the central nervous system (CNS), comprised of the brain and spinal cord. That barrier is often an obstacle for CNS-targeting therapies.
NDC-1308 in preclinical studies
Preclinical studies, partly supported by a research grant from the National Multiple Sclerosis Society, have evaluated NDC-1308 treatment in animal models of demyelination.
After treating mice with cuprizone, a toxic molecule that causes damage to myelin, the animals received a daily injection of NDC-1308 for two weeks. The dose was 50 mg/kg of body weight.
Results showed that the compound increased the number of myelin-producing oligodendrocytes by 20% and promoted remyelination in the hippocampus, a region primarily associated with memory and cognition.
A higher dose of 68 mg/kg was also tested for six weeks. In these animals, there was an 18% increase in myelin in the cortex, the outermost region of the brain, and a 44% in hipoccampal myelin, compared with animals receiving a placebo for the same amount of time. After three weeks, mice also exhibited increased muscle strength compared with animals treated with a vehicle solution or estradiol.
In animals with experimental autoimmune encephalomyelitis, a disease that resembles MS in mice, treatment with NDC-1308 after disease induction delayed the onset of symptoms and preserved neuronal cells, suggesting a neuroprotective effect of the medication.
Due to the similarities between NDC-1308 and estradiol, researchers also investigated if the experimental compound had estrogenic effects. This was assessed by the therapy’s ability to promote the proliferation of cells in the uterus of female mice. In contrast with estradiol, which exhibited estrogenic properties from doses of 0.01 mg/kg, no significant estrogenic activity was observed for NDC-1308 up to a dose of 60 mg/kg.
Common side effects of NDC-1308
NDC-1308 has not yet been tested in clinical trials, and its most common side effects remain unknown. In animal studies, the compound didnāt show harmful side effects commonly related to estradiol, including the ability to cause genetic changes or damage to the DNA. The investigational treatment also is not expected to cause abnormal heart rate.
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