Clues that could aid medical researchers in the quest to repair spinal cord injuries in humans have just been gleaned from an unlikely source: a class of ancient jawless fish called lampreys.
These eel-like creatures branched away from the evolutionary lineage that led to all jawed vertebrates (including other fish and us) about 550 million years ago, and they haven’t changed much in appearance in at least 100 million years. Yet their primordial style belies a remarkable physiological adaptation: Lampreys can recover from a completely severed spinal cord in about 10 to 12 weeks.
(Another skill worth noting: Lampreys can scale waterfalls with their nightmare-inducing sucker mouths when they head upstream to spawn.)
When investigating the genetic basis of the lamprey’s nerve regeneration, an international group of researchers, including scientists from the Marine Biological Laboratory at the University of Chicago, found that many of the genes crucial to the process are also found in humans.
“We found a large overlap with the hub of transcription factors that are driving regeneration in the mammalian peripheral nervous system,” said study co-author Dr Jennifer Morgan in a statement.
In a paper published in the journal Scientific Reports, Morgan and her colleagues closely monitored the lamprey healing process by taking tissue samples from the fish’s brains and spinal cords at various time points, from right after full paralysis was induced to complete healing at 3 months.
The team found that many of the genes switched on in the damaged tissue encoded for molecules belonging to the Wnt signaling pathway. This family of proteins – conserved in organisms ranging from roundworms to Homo sapiens – guides the formation of the body's shape and layout during early embryonic development and oversees stem cell differentiation. However, some Wnt proteins can block specialization in neural stem cells to maintain a population of cells with regenerative properties.
When lampreys were given a drug that inhibits Wnt signaling, they never recovered their ability to swim.
An additional valuable insight came from the team’s observation that healing lampreys also display high levels of altered gene activity in the brain. This indicates that future spinal cord therapies may need to target more than just the site of injury.
"This reinforces the idea that the brain changes a lot after a spinal cord injury," said Morgan. "Most people are thinking, 'What can you do to treat the spinal cord itself?' but our data really support the idea that there's also a lot going on in the brain."
The group’s next step is to tease out the particulars of the self-repair mechanism, eventually determining whether it can be applied to other animals.
"In this study, we have determined all the genes that change during the time course of recovery and now that we have that information, we can use it to test if specific pathways are actually essential to the process," added co-author Dr Ona Bloom.