The KCL-286 Pill: Regenerating the Ability to Walk

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Issue 1, Volume 114

By Erica Wong 

Trailing from the brain to the lower back is a long tubular structure known as the spinal cord. This cord carries nerve impulses from the brain to the body, allowing the joints, muscles, and tissues to move based on the brain's commands. Unfortunately, nearly 250,000 to 368,000 people a year suffer from spinal cord injuries that severely impact their daily lives. Those with spinal cord damage often lose bodily function and mobility from their injuries, and many are unable to walk. In past years, researchers have been unable to discover a human-safe drug that could resolve the symptoms of spinal cord injuries.

Spinal cord injuries arise when forceful impact occurs to the tight bundle of nerves that sends and receives signals throughout the body. The causes can range from spontaneous vehicular crashes to degenerative diseases. Spinal cord injuries can directly impact the spinal cord nerves or indirectly damage the bone, tissue, and vertebrates surrounding the spinal cord. Depending on the site of the injury, symptoms from a spinal cord accident can be temporary and moderately serious or permanent and deadly. Symptoms from spinal cord damage include limited bowel function and movement, trouble breathing, and pain throughout the day.

After years of being unable to find a cure for this strenuous disability, there may be hope at the end of the tunnel. New research published in the British Journal of Clinical Pharmacology by Professor Jonathan Corcoran and his team found that a drug called KCL-286 has provided favorable results for spinal cord-injured patients within a phase I clinical trial. KCL-286 is an oral pill that acts as an agonist: a chemical substance that binds to a receptor and activates it. For patients with spinal cord injuries, KCL-286 activates a receptor called RARβ2, which stimulates axonal outgrowth. 

Axonal outgrowth is a process that enables axons, thin fibers that transmit impulses in the neurons, to link to distant target cells. Once the axons link to target cells, the brain is able to command the body to move around using the impulses within axons. Patients with spinal cord injuries typically have limited axonal outgrowth because their axons are crushed and can not connect to the target cell. KCL-286 promotes the creation of a RARβ2 protein, which stimulates axonal outgrowth through regeneration of existing axons. This process may help patients regain functionality throughout their bodies.

In order to test the effectiveness and limits of the KCL-286 drug, 109 healthy males were placed into one of two trial groups: a single ascending adaptive design with food interaction (FI) and a multiple ascending dose arm (MAD). The single ascending dose adaptive design FI established the safe dosage range of medicine needed in an experiment by gradually increasing the dosage of KCL-286 over time. Researchers specifically looked for side effects of the drug and measured how KCL-286 is processed within the body. On the other hand, the multiple ascending dose arm explored how the body interacts with the medicine and investigated the drug’s harmfulness in the body. 

Researchers evaluated these two criteria using the patient’s white blood cells to determine the amount of activated RARβ2 protein. Results showed that KCL-286 increases RARβ2 produced within the body, which indicates there should be an increase in axonal outgrowth. Though there are no definitive results—like the immediate ability to walk—the correlation between increased axonal outgrowth and the ability to move seems promising in slowly regenerating sensory skills over time. Furthermore, after observing the patients over a three-month period, researchers concluded that patients could safely ingest 100 milligrams of KCL-286 with no adverse side effects.

There are lingering unknowns of the experiment to address in future studies. Firstly, the trial had no female participants, because at the time, no female reproductive toxicology data was completed. In addition, the male participants were all between ages 19 and 45, did not take over-the-counter medications, and were not overweight. There are more variables to consider, such as the effect of KCL-286 on other types of participants, the long-term effects on current patients, or the time frame between when axonal outgrowth occurs to when a patient has full mobility. Despite needing further investigation, this study has broadened the research possibilities on curing spinal cord injuries. Currently, the researchers are pending approval for a phase II clinical trial, which should include more participants and variety within the testing groups. Perhaps in the future, with lots more research and experimentation, researchers may be able to regenerate the movement that people have lost completely.