The research by Cavalli, Dunn, et al is innovative not only for its use of neuroprotective drugs but also because the team developed a platform for developing molecular approaches to neurological disorders. The drug discovered by them targets damaged sensory nerves of the CNS. Instead of treating the symptoms of that disorder, the researchers aim to treat the cause.
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Why was this needed?
Sensory neuritis of the CNS (usually following spinal cord injury) is a common, debilitating medical condition. Based on the research findings, many people who are living with spinal cord injury not only deal with paralysis but they experience neuropathic pain and malfunctioned sensory processing which is a significant reason for their poor quality of life. Neuropathic pain is a type of pain caused by nerve problems, which may affect how well the nerves work. Neuropathic pain is chronic pain and lasts months if not years.
When sensory neuritis happens in the peripheral nervous system, these neurons quickly heal. However, achieving the same result in the CNS requires the induction of supporting glial cells to improve neuronal regeneration. This can be achieved using drugs from the fibrate class such as fenofibrate. Fenofibrate operates by improving myelination (the production of the myelin sheath that covers sensory nerves and aids nervous transmission).
Fenofibrate improved the sensory-spiking connections between neurons by a magnitude of over two dozen, and it caused the growth of sensory-spiking connections from both sides of the injury as well as the growth of the sensory-spiking connections themselves. In the words of the team, “Our study shows that fenofibrate activates support cells, that are related to hair cells, which may be an important mechanism for how the drug improves recovery. Because fenofibrate is already approved for human use, identifying its potential as a treatment for sensory disorders opens the door for possible repurposing of the compound to treat nerve injuries in patients”.
The researchers clearly distinguished the peripheral nervous system from the central nervous system with a special type of cell. This cell has its cell body in the peripheral nervous system, but its axon enters the central nervous system. After creating an injury on both parts, the axon in the CNS did not recover fully compared to the parts in the periphery. Valeria worked with Oshri Avraham (a staff scientist) to show that support cells in the CNS didn’t fully express the PPAR-alpha pathway, but support cells in the periphery did. This formed the basis for fenofibrate, which activates the PPAR-alpha pathway. PPAR-alpha is a nutrient sensor found in brain cells and some types of glial cells; it has a vital role in stimulating axon growth.
Fenofibrate being an already approved drug by the Food and Drug Administration is a stepping stone for other nervous deformity research. It is an additional and highly effective tool we can use to restore function after nerve injury. A day is coming when a transecting spinal cord injury will be almost as easy to treat as a shin bruise.