A major focus in recent years has been unraveling the genetic factors contributing to spina bifida. With advances in DNA sequencing, researchers are conducting genome studies on families affected by neural tube defects. In 2025, a groundbreaking study by Ha and colleagues used whole genome sequencing on families with spina bifida and found that de novo (new) mutations in certain genes account for nearly 25% of cases examined (Shatto, 2025). This study identified clusters of mutations affecting how embryonic cells adhere and signal to each other, shedding new light on the molecular steps of neural tube closure. Implications from studies like this are intriguing because if we know which genes are involved, we can develop targeted interventions and better genetic counseling.

At the same time, scientists have been investigating the biological pathways behind neural tube closure. Animal models have been instrumental here. By studying mice that develop spina bifida due to specific gene knockouts, researchers pinpoint the roles of those genes (van Straaten & Copp, 2001). An intriguing area of research is nutritional genomics—understanding why some neural tube defects are folate-resistant and what other nutrients might help. Scientists are looking at vitamins like B12, choline, and betaine, which are all intertwined with folate metabolism. There is also research into whether mothers with certain microbiome compositions or metabolic issues might require personalized nutrition to prevent NTDs.

The curly tail and loop-tail mouse models have been mentioned before when discussing Tissues Affected. These and other animal models are critical for studying spina bifida because they allow controlled experiments that can’t be done in humans. Researchers have at their disposal not just mice, but also rats (some strains can be induced to have NTDs via drugs or diet), chick embryos, zebrafish (transparent embryos where cellular movements can be observed), and even frogs for basic neural development studies. Each model has its strengths. For instance, the advantage of mouse models is that their genetics are very similar to humans and one can knock out specific genes to see the effect. The curly tail mouse has a mutation causing delayed closure of the posterior neuropore, very analogous to human lumbar spina bifida (Seller & Adinolfi, 1981; Sudiwala et al., 2016). Through this model, scientists discovered that folic acid alone did not prevent spina bifida in those mice, but a combination of folate plus other metabolites (like formate or inositol) could prevent it (van Straaten & Copp, 2001). This directly inspired clinical research to see if inositol could help human mothers with prior NTD pregnancies (initial small trials suggest it might). The loop-tail mouse, caused by a mutation in VANGL2, provided the first proof that the planar cell polarity pathway is essential for neural tube closure. That, in turn, led researchers to screen human babies for VANGL mutations, which were found in some cases (Galea et al., 2018).

Animal models are also used to test potential therapies. Before a new treatment is tried in people, it’s usually studied in an animal model of the disease. For example, the fetal surgery with stem cells mentioned earlier was developed through experiments in sheep. Fetal lambs with created spina bifida defects were operated on and given stem cell patches to see if it improved healing of the spinal cord. Similarly, advancements in shunt technology or in surgical closure techniques often come from lab research using mannequins or animal tissue.

On the surgical front, research is very active in refining fetal surgery. There are currently clinical trials and registries tracking outcomes of babies who had fetoscopic repairs versus open repairs, to establish best practices. Engineers are developing better surgical instruments for use in the womb, such as flexible fetoscopes and even robotic-assisted systems to make fetal surgery safer. Another surgical research area is improving the durability of shunts or finding better treatments for hydrocephalus (like ETV-CPC as an alternative to shunts in spina bifida infants).

In rehabilitation, research includes developing advanced orthotic devices and even exoskeletons that can help individuals with paralysis to walk. For instance, some adolescents with spina bifida are testing robotic leg braces (exoskeleton suits) that enable guided walking practice, which can strengthen muscles and improve bone density. Studies are also ongoing to address secondary issues: for example, preventing latex allergy by exposure avoidance (which has decreased allergy rates in new generations), or managing obesity which can be common in teens with spina bifida due to reduced mobility.

Another vital aspect of research is the Spina Bifida Patient Registry maintained by the CDC (Centers for Disease Control and Prevention [CDC], 2024a). This registry collects data from patients across the U.S. to understand the long-term outcomes and complications they face. By analyzing this data, healthcare providers can see trends (for example, how common renal issues are in adults with spina bifida, or what interventions correlate with better mobility) and update care guidelines accordingly. In fact, the Spina Bifida Association has published comprehensive care guidelines (latest in 2018) covering everything from prenatal counseling to adulthood, which are informed by ongoing research findings (Church et al., 2020).