Cancer treatment has many debilitating side effects, not the least of which is chemotherapy-induced peripheral neuropathy (CIPN). Up to 85% of chemo patients experience CIPN, characterized by chronic burning pain, tingling, decreased sensation, and increased sensitivity to touch.

Currently, there are few treatment options for the condition. The primary one is morphine, which comes with serious risks.

But, in a few years, the quality of life for individuals living with CIPN could vastly improve. That’s the hope of the scientists at biopharmaceutical company Kannalife, who created a new compound that, in highly predictive animal models, has successfully reversed CIPN.

What Is KLS-13019?

The compound in question, KLS-13019, is an iteration of cannabidiol (CBD), one of the 113 identified cannabinoids in the cannabis plant. Medicinal chemist Bill Kinney, Ph.D., chief scientific officer at Kannalife, created it during a successful attempt to increase CBD’s water-solubility. The goal was to boost CBD’s bioavailability and use it in a pill form. The result was a new, now-patented molecule with improved potency — and safety.

“CBD has a dark side,” Doug Brenneman, Ph.D., member of Kannalife’s scientific advisory board, says. “At concentrations only two times higher than its beneficial concentration, it produces neural damage.”

Dr. Brenneman has been studying neurodegeneration for the past 35 years. He served as a section chief at the National Institutes of Health, leading research into the developing nervous system. With KLS-13019, he’s especially excited that his team created a separation factor of five between efficacy and toxicity.

In addition, Dr. Brenneman says, the compound has more pharmacological specificity than CBD.

“One of the real conundrums of CBD is it interacts with many drug target molecules. There are dozens,” he explains. “That’s good because it broadens CBD’s pharmacological value in preventing disease. But … we like to have a drug highly directed to the therapeutic target, and that’s exactly where we ended up.”

How Does KLS-13019 Work?

“When we give a chemotherapeutic agent, like Paclitaxel, which we’ve used for all our studies, there’s an acute toxicity … on the sensory neurons … related to oxidative stress,” Dr. Brenneman says. “Then there’s a chronic phase, which happens over weeks and months, where you get this excruciating pain in the hands and feet that can become permanent. That’s the unmet medical need in this field.”

The question for the researchers then became: To what extent can you prevent this pain from occurring, both acutely and chronically?

Animal studies and cell cultures show CBD and KLS-13019 can prevent CIPN if administered before chemo. However, research indicates that only the latter is effective at reversing CIPN — “like morphine, but without the abuse potential,” Dr. Brenneman says. “Our compound is directed at sensory neurons and the ability to block oxidative stress, whatever the cause is.”

He adds: “We’re saying that if you treat it early enough … you may even be able to reverse [CIPN] in a timely fashion.”

The Challenges of KLS-13019

So, what’s the catch? Dr. Brenneman calls out the danger of CBD in general.

“People say CBD is safe, but have they looked?” he says. “Our studies show that, at a high enough concentration and long enough duration, hippocampal neurons are not happy around CBD … There’s a potential problem with

damage and cell death in the developing nervous system.”

For CIPN patients, there is more good news, though. Dr. Brenneman says the research indicates the drug will not affect liver enzymes, unlike the CBD-based Epidiolex, which the FDA has approved for use in children with epilepsy. There are also no indications the compound contributes to heart arrhythmia, but more research is needed.

“We still want to know if there are any dangers to the developing nervous system, and we need to know the exact pharmaco-kinetic properties,” he continues. “The rest is just going through all the boxes you need to check. It’s still very early stages.”

What Should Clinicians Know

Based on his extensive CBD research, Dr. Brenneman says his ultimate takeaway for clinicians — aside from the unique capabilities of KLS-13109 — is that recommending CBD is ultimately advising patients to take an unregulated product (except FDA-approved Epidiolex).

“We need more work done on the formulation CBD is in,” he explains. “We need to have a stable formulation that has a reproducible effect on the patient.”

Dr. Brenneman acknowledges the desire to help refractory patients with pain and other disorders where current therapies don’t work well. But he warns providers that even if there is “a source they feel confident in, it still comes back to this formulation issue.”

He continues: “It’s all doomed until these things are in reproducible preparations. That’s square one. Until that problem is solved, you don’t know what you will have.”