FDA-approved drug could be repurposed to relieve osteoarthritis pain and protect cartilage: ScienceAlert

Researchers are always looking for drugs that can be repurposed for something else. The main advantage is that these treatments have already passed various safety tests, making them available more quickly for new pathologies.

Now a team from Yale School of Medicine in the US has found that the epilepsy drug lacosamide may also be effective in osteoarthritis – not only to relieve the associated pain, but also to reverse some of the damage it causes to joints.

Osteoarthritis occurs when the cartilage that cushions and lubricates between bones is damaged and worn away. Current treatments can manage pain, but there is no real solution other than replacement surgery (which can bring its own problems).

The results of the lacosamide tests, published in Bioactive materialsshow that in mouse models and human cartilage cells in the laboratory, it is able to promote cartilage repair, slow down its deterioration and reduce accompanying pain.

Additionally, the researchers identified a “sweet spot” where the drug was most beneficial, which will be helpful in further developing the treatment.

“There is an optimal range in which the medication helps restore balance without overcorrection,” says musculoskeletal biologist Chuan-Ju Liu. “What stood out was not only its effectiveness, but also the low dose needed.”

“This tells us that the system is perfectly tuned.”

Researchers were led to lacosamide because it is a sodium channel blocker. In a previous study, some of the same researchers identified a sodium channel and protein called Nav1.7 as being involved in both sending pain signals to the brain and regulating the formation and breakdown of cartilage.

Nav1.7 is active inside special cells called chondrocytes, which manage the balance between removing old tissue and adding new tissue. Osteoarthritis disrupts this balance, tipping the scales toward cartilage loss, and Nav1.7 is an important factor in this. In a joint affected by osteoarthritis, Nav1.7 is more active than it should be.

“When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain,” says Liu.

“Our results suggest that Nav1.7 is a dual-action target. By blocking this unique protein, we can potentially soothe painful nerves and tell cartilage cells not only to stop breaking down, but also to start repairing themselves.”

Essentially, lacosamide reduces Nav1.7 activity, and published research shows the impact it can have on cartilage and pain.

The team also wanted to find the best way to administer the drug and found that injecting it directly into the affected joint in mice worked better than giving it orally, even at lower doses.

The problem was that it didn’t stay long once inside, which meant repeated injections were needed to keep it working.

In injection testing, lacosamide was packaged in a gel to counteract the “leaky bucket” nature of the joints which can quickly dissipate any liquid treatment.

“The hydrogel acts as a local reservoir,” says Liu. “It keeps the medication in place where it’s needed most and releases it slowly over time. It turns a daily pill into a long-lasting topical treatment that stays active for a month or more.”

All of this must of course be tested on real osteoarthritis patients, but the first signs are promising. As we mentioned at the beginning, lacosamide’s status as an approved epilepsy drug means that the time frame for clinical testing is expected to be shorter.

Previous research suggests that lacosamide may indeed be effective as a pain reliever, although previous work has been linked to another Nav1.7-related condition.

If the drug can be further developed for the treatment of osteoarthritis, then the potential is enormous for the hundreds of millions of osteoarthritis sufferers around the world: a drug that not only numbs the pain associated with the disease, but also brings back lost cartilage.

“There is a major unmet need in osteoarthritis,” says Liu. “We need therapies that don’t just mask pain, but actually modify disease progression.”

The research was published in Bioactive materials.