Study: Chronic Spinal Cord Injury Can Be Improved by Epigenetic Activator

10/22/2022|Updated: 10/22/2022

It’s been acknowledged that there is no effective treatment to reverse injury to the spinal cord, but a recent study revealed positive findings from a mouse study.

Mice with severe spinal cord injury were given weekly treatments with an epigenetic activator, and the experiment results revealed that the treatments helped stimulate motor and sensory axon growth, sprouting, and synaptic plasticity in the injured spinal cords.

The study was published in the journal PLOS Biology, and was led by Simone Di Giovanni at Imperial College London in the U.K.

In the experiment, adult 6-to-8-week-old mice with destroyed spinal cord T9, mimicking severe clinical spinal cord injury, received a dosage of TTK21 via intraperitoneal injection (a means of administering substances usually used in animals like mice) once per week starting 12 weeks after injury.

TTK21 is an activator of the histone acetyltransferases CBP/p300 (epigenetic enzyme). Researchers postulated that this activator might enhance neuronal plasticity, regeneration, and functional recovery.

It is said that the mice lived in an enriched environment, giving them opportunities to be physically active. After 10 weeks of treatment, many improvements were shown in the mice compared to the control group (treated with nanoparticles and vehicle alone).

Researchers found that more axons sprouted in the spinal cord. The retraction of motor axons above the point of injury halted, and the sensory axon growth also increased. Researchers discovered these changes due to the observed increase in gene expression related to regeneration.

According to the data analysis, TTK21 enhanced classical regenerative signaling in ganglia sensory (located on the dorsal roots of spinal nerves), but not cortical motor neurons. TTK21 also stimulated motor and sensory axon growth, sprouting, and synaptic plasticity, but failed to promote neurological sensorimotor (a decrease of mobility and sensation due to nerve damage) recovery.

In the next step, researchers want to enhance those effects more, and stimulate the regenerating axons to reconnect to the rest of the nervous system to facilitate easier mobility in animals.

“This work shows that a drug called TTK21 that is administered systemically once/week after a chronic spinal cord injury (SCI) in animals can promote neuronal regrowth and an increase in synapses that are needed for neuronal transmission,” said Di Giovanni. “This is important because chronic spinal cord injury is a condition without a cure where neuronal regrowth and repair fail. We are now exploring the combination of this drug with strategies that bridge the spinal cord gap, such as biomaterials, as possible avenues to improve disability in SCI patients.”