Spinal cord injury has long been one of medicine’s most frustrating frontiers. Once damaged, neurons in the spinal cord and brain rarely regenerate, leaving patients with permanent paralysis and loss of motor function. But researchers at the University of California, San Diego School of Medicine may have uncovered a path toward recovery. Using powerful bioinformatics tools, they have identified an existing drug – Thiorphan – that could stimulate neurons to regrow and restore lost function.
Their study, published in Nature, shows how modern computational biology can accelerate discovery, turning data into potential cures at unprecedented speed. “This represents a convergence of technologies,” explained Dr. Erna van Niekerk, lead author of the study. “Gene sequencing, computational bioinformatics, and cell culture all came together to identify a potentially useful treatment that might have taken decades before these tools were available.”
From Computer to Lab: A Data-Driven Discovery
The project began with a deceptively simple question: what makes certain neurons capable of regenerating after injury while others remain dormant? Researchers analyzed the gene expression patterns of mouse neurons that successfully regrew after spinal cord injury, then searched for drugs that could reproduce that same pattern in human neurons.
Using the massive Connectivity Map database, which catalogs the genetic effects of thousands of compounds, the team zeroed in on Thiorphan—a drug once tested in humans for unrelated conditions. When applied to cultured adult human brain cells, Thiorphan dramatically increased neurite outgrowth, the early process by which neurons form new connections.
Growing adult human brain cells in the lab is notoriously difficult, making this finding both rare and significant. “We succeeded in culturing adult human brain cells in large numbers,” said senior author Dr. Mark H. Tuszynski. “That’s a powerful new tool for discovering treatments for neurological disorders.”
What Is Thiorphan?
Thiorphan is a neutral endopeptidase inhibitor, meaning it blocks enzymes that normally degrade certain signaling molecules in the nervous system. By doing so, it appears to trigger a “developmental reset,” nudging adult neurons back into an embryonic-like state where they can grow and repair.
In animal studies, Thiorphan boosted the production of brain-derived neurotrophic factor (BDNF) and phospho-AKT—two key proteins involved in cell survival and neural growth. These molecular shifts mirror those seen during early brain development, suggesting that Thiorphan reawakens dormant growth pathways within the nervous system.
Testing in Animals and Humans
After promising results in cultured neurons, the UC San Diego team tested Thiorphan in rats with severe cervical spinal cord injuries. When the drug was combined with neural stem cell grafts, the treated rats showed a twofold improvement in forelimb function compared to untreated animals. Even rats receiving Thiorphan alone regained roughly 50 percent more hand function than controls.
Microscopic analysis revealed that Thiorphan increased corticospinal axon regeneration—the growth of nerve fibers essential for voluntary movement—by 60 percent. In primate and human neuron cultures, Thiorphan continued to demonstrate strong regenerative activity, increasing neurite length and density by up to 61 percent.
The Mechanism Behind Regeneration
The researchers propose that Thiorphan reprograms injured neurons to a regenerative state by altering gene expression. RNA sequencing of treated monkey neurons revealed activation of 177 genes linked to neural development, synapse formation, and growth signaling.
In rats, Thiorphan-infused brain regions exhibited elevated levels of BDNF and phospho-AKT, two molecules central to nerve growth and repair. Together, these findings suggest that Thiorphan acts like a biochemical time machine—reverting mature neurons to a developmental phase where regrowth becomes possible.
Toward Clinical Trials
Because Thiorphan has already been tested in humans for non-neurological conditions, it could advance rapidly to clinical trials for spinal cord injury. The UC San Diego team is already optimizing its use, exploring delivery methods that might bypass the need for direct brain infusion. “We are making efforts now to optimize Thiorphan for future clinical trials,” said van Niekerk. “That process is simplified by the fact that the drug has already been used safely in people.”
Thiorphan’s discovery marks a turning point in regenerative neuroscience. For decades, spinal cord injuries were seen as irreversible. This research challenges that view, suggesting that the brain’s regenerative potential can be pharmacologically unlocked.
Dr. Tuszynski believes the approach could extend beyond spinal cord injury to other neurological disorders. “The ability to culture adult brain cells could be useful for testing new drugs or gene therapies for many brain diseases,” he said.
While significant hurdles remain—such as confirming long-term safety, improving delivery methods, and scaling up production—the study offers new hope to millions living with paralysis. By combining bioinformatics, stem cell science, and molecular biology, UC San Diego’s team has not only discovered a potential treatment but demonstrated a new model for rapid drug discovery.
If successful in clinical trials, Thiorphan could become the first therapy to truly regenerate the human spinal cord—transforming a once-impossible dream into a scientific reality.
