ST. LOUIS, Mo. — Fenofibrate is probably a familiar name to many patients trying to watch their cholesterol. However, a new study reveals the common prescription drug may also be able to repair major spinal cord injuries. Researchers from the Washington University School of Medicine in St. Louis have discovered that fenofibrate has the power to help the body heal injuries — even those severe enough to cause paralysis.
The study finds this FDA-approved drug for lowering cholesterol stimulates “support cells” in the central nervous system. These cells encourage the body’s sensory neurons to regrow after an injury.
Why are spinal cord injuries so devastating?
Damaging your spinal cord can be a life-changing and even life-threatening injury because it disrupts the communication between the brain and the body. Making matters worse, researchers say damaged motor and sensory neurons in the central nervous system (meaning anywhere around the brain and spinal cord) have less ability to heal in comparison to nerves elsewhere in the body. This is why people who suffer this kind of injury often deal with chronic pain, numbness, and paralysis.
On the other hand, peripheral sensory nerves (meaning those allowing you to feel things in your limbs) are able to heal and function again after an injury. This explains why a deep cut in your leg doesn’t leave that area numb forever.
The new study found that the support cells around these nerves express certain genes which promote regeneration after an injury. Unfortunately, the same cells around the spinal cord don’t do this, explaining why central nervous system damage heals so poorly. Moreover, the team says fenofibrate sparks these support cells to begin the regeneration process.
“When people think of spinal cord injury, they tend to think of paralysis, but there are a lot of problems with sensory processing and pain after spinal cord injury as well,” says senior author and professor of neuroscience Valeria Cavalli, PhD, in a university release. “Addressing those sensory issues could go a long way toward improving quality of life for survivors. Our data indicate that fenofibrate has the potential to activate these support cells and improve recovery, which means we could potentially repurpose this FDA-approved compound to help restore sensory function after nerve injuries.”
In experiments with mice, study authors found that fenofibrate helped the animals to regrow their sensory neurons twice as fast than those taking a placebo.
Paving the pathway to regeneration
To find out why regeneration differs throughout the body, Cavalli and the team studied a unique type of cell that appears around both the central nervous system and the peripheral nerves. Scientists call these cells sensory neurons of the dorsal root ganglia.
The cells gather together into a structure called a ganglion which sits near the spinal cord. Long, thin “arms” called axon branches come out from each of these cells and go in two different directions — one going to the central nervous system and one traveling throughout the body.
Despite these branches being part of the same cell structure, the study finds they end up reacting differently to injury depending on the location of the damage. Cavalli and first author Oshri Avraham compared the gene expression of five kinds of ganglion support cells in injured mice.
Their results revealed that, after an injury, support cells called satellite glial cells increase the expression of a set of genes called the PPAR-alpha pathway. This pathway plays a major role in fat metabolism. Interestingly, however, this fat metabolism response only appeared to fix damage to peripheral sensory nerves. Moreover, the gene pathway actually displayed less activity around injuries to the spinal cord.
So how does fenofibrate fix this?
Cavalli and Avraham say the drug activates PPAR-alpha expression, which appears to promote regeneration in humans and animals. Researchers fed the injured mice fenofibrate or a placebo for two weeks. Just three days after their spinal cord injuries, mice taking the drug showed twice the amount of growth in the central branches of the sensory neuron axons.
“PPAR alpha is only expressed in satellite glial cells, not in neurons, so these results tell us that targeting these support cells can improve regeneration and potentially relieve sensory symptoms like pain,” Cavalli concludes. “It gives us an additional tool to design therapies to restore function after nerve injuries. We haven’t fixed spinal cord injury, but we’re one step closer to figuring out how to do it.”
The findings appear in the journal eLife.