For Louzada, the initial phase of the research has limitations that make it difficult to interpret the results reported so far. The most critical issue, he says, is the possibility that some patients received the substance while still in the spinal shock phase, a period of neurological instability that can mask the true diagnosis of the injury.

At least one of the patients may have received the injection less than 24 hours after the trauma, he says. Spinal shock—a phase during which the body may suppress all motor, reflex, sensory, and autonomic activity below the level of the injury—usually dissipates within 72 hours, a window that coincides with the protocol established for the polylaminin injection.

The problem is that during spinal shock an incomplete injury with real potential for recovery may be mistakenly classified as complete. If improvement occurs after treatment, it becomes impossible to distinguish the effect of the substance from the natural progression of the injury.

Louzada also notes that the preprint does not explicitly mention whether the bulbocavernosus reflex test was performed, considered the clinical marker that spinal shock has ended. The paper instead refers to the evaluation of deep anal sensation and voluntary contraction of the anal sphincter, tests that differ from the reflex test itself.

Absence of a control group and confirmation bias

The absence of a control group is another central point of the criticism. Studies indicate that between 10% and 30% of patients with spinal cord injury may show some spontaneous improvement or be reclassified after the acute phase, making a comparison group even more necessary to isolate the effect of the substance being tested.

According to Louzada, the enthusiasm generated by the public attention surrounding the case—along with intense activity on social media and extensive media coverage—increases the risk of confirmation bias, a situation in which researchers may interpret results in ways that support the hypothesis they wish to confirm. 

However, the researcher believes the methodological problem is not new. In his view, it existed even before the issue drew national attention and simply became more visible once the data became accessible to the scientific community. Below is an interview with Paulo Louzada for Science Arena. 

Science Arena: One of the central points in the debate is the absence of a control group. Is it possible to move on to phases 2 and 3 without a randomized, double-blind control group?

Paulo Louzada: Without a control group and without blinding, we cannot say whether polylaminin works or not. At best, we would remain in the realm of “high probability” or a “strong hypothesis.” No study of a new drug advances to routine clinical practice without a randomized, double-blind clinical trial. One possible exception would be if a statement made by Professor Tatiana on the Roda Viva program [February 23] were confirmed: if 30 patients were able to walk again in a compassionate-use study, this might eliminate the need for a control group. Even then, it would be essential to ensure that the patients were no longer in the spinal shock phase.

The treatment is administered within the first 72 hours after the trauma, a period during which spontaneous recovery may occur. How can the effect of polylaminin be distinguished from the natural course of the injury?

This can be determined by confirming the return of the bulbocavernosus reflex. Once this reflex returns, the neurological examination becomes reliable. If the patient truly has a complete spinal cord injury, the chance of spontaneous recovery—even with traditional treatment such as decompression surgery and physiotherapy—is less than 1%. The likelihood of regaining the ability to walk independently under these conditions, with rigorous confirmation of a complete injury, is virtually zero.

Studies show that between 10% and 30% of patients may experience some spontaneous improvement or be reclassified after the acute phase. How does this affect interpretation of the results?

It is uncertain whether the patients treated with polylaminin were already beyond the spinal shock phase, a detail that does not appear explicitly in the preprint. For this reason, the possibility of spontaneous improvement must be considered in patients who may in fact have had incomplete injuries masked by spinal shock. In my view, the methodological design will need to be reformulated in future applications so that the results can be established with greater confidence.

Is there a risk of observation bias or therapeutic enthusiasm in a context of intense public pressure and high expectations among patients?

Yes. Scientists must remain skeptical of their own results and always consider the possibility that a finding may have occurred by chance. Starting from the premise that the drug may not work helps prevent confirmation bias. 

The Brazilian Health Regulatory Agency (ANVISA) has authorized only a phase-1 study focused on safety. What would be the minimum criteria for evaluating the effectiveness of polylaminin?

A placebo-controlled, randomized, double-blind study with a larger number of patients would be required.

Can compassionate use and court-ordered decisions compromise the production of scientific evidence?

It certainly can. Court-ordered administration of polylaminin in patients with spinal cord injury—especially when carried out by professionals not trained in the study’s methodology—is a distortion. This type of research should be conducted exclusively by the neurosurgeons responsible for the protocol. When the procedure is performed by professionals not trained in the technique, the risk of errors increases, as does the risk of false-negative results—situations in which the patient might improve but does not because the substance was administered improperly.

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From this substance, scientists have created a molecule called polylaminin, which may influence the treatment of spinal cord injuries.

Though related, laminin and polylaminin differ in both origin and action within the human body. While laminin is produced naturally during pregnancy, polylaminin is created in the laboratory, as we explain in this article.

Function of laminin

Laminin helps in the development of neurons and in the process of cell adhesion. This protein, abundant in the placenta, establishes connections between cells, especially in the nervous system.

It is most influential during fetal development in the uterus.

Many substances produced to support pregnancy are discarded shortly after birth. At this stage, several proteins created to provide structural support during gestation, including laminin, can be eliminated.

Polylaminin and its action in the body

In the search for effective treatments for spinal cord injuries, scientists at the Federal University of Rio de Janeiro (UFRJ) developed a new version of laminin called polylaminin.

The relationship between polylaminin and the placenta is linked to its origin, since it is derived from laminin found in this temporary organ. Experiments analyzing its effect on spinal cord injuries showed that it can help reestablish nerve connections.

The new molecule is even more effective when administered within 72 hours after trauma. In a study conducted on paraplegic dogs, scientists observed functional improvement in the animals. 

The effect was stronger when combined with certain adjuvants, as this approach helped break down scar tissue.

Using a substance derived from a natural protein found in the placenta, scientists sought to develop a therapeutic approach capable of promoting significant regeneration in spinal cord injuries.

To read the full article on polylaminin, visit this piece from Science Arena.

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The molecule, known as polylaminin, is a reconstituted form of laminin, a protein essential for the organization of the nervous system during embryogenesis. 

An unprecedented clinical study

The first results in humans were published as a preprint in medRxiv in February 2024. The study involved eight patients who had sustained complete spinal cord injuries, a condition that historically carries less than a 15% chance of motor recovery without intervention.

Participants received a single intraparenchymal injection of polylaminin an average of 2.3 days after the trauma. 

Of the eight volunteers, six survived, demonstrating recovery of voluntary motor contractions below the level of injury—an outcome considered unprecedented in such cases.

Recovery was documented using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale and evoked potentials.

Bruno Drummond, a participant who was left quadriplegic after a car accident, was among the first to show improvement.

Consistent evidence in animal models

Before advancing to human trials, the researchers gathered a robust body of experimental evidence. In an article published in Frontiers in Veterinary Science (2025), the team tested the substance in paraplegic dogs with chronic injuries. 

Previous studies in rodents had also shown that the substance reduces inflammation, limits tissue loss, and promotes axonal regeneration across multiple models of spinal cord injury.

Regulatory and scientific obstacles

Despite the excitement, the transition from laboratory research to clinical use faces several barriers. Cristália, a Brazilian pharmaceutical company and partner in the development, is awaiting authorization from Brazil’s health regulatory agency ANVISA to begin phase-2 clinical trials in public hospitals in the state of São Paulo.

ANVISA states that additional data from preclinical studies are still required, particularly regarding pharmacological stability and reproductive safety. 

“These studies are essential in determining whether the product can proceed to the next phase of testing in humans,” the agency said in a statement sent to news outlets.

In addition, a full understanding of its action mechanism—whether it depends solely on the structure of the extracellular matrix or also involves direct cellular modulation—remains under investigation.

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