Intrauterine Treatment of Spina Bifida: Primate Model

Abstract

A spina-bifida-like condition was induced in 8 Macaca mulatta fetuses by intra-uterine lumbar laminectomy (L3-L5) followed by displacement of the spinal cord from the central canal. This condition was repaired in utero in 5 animals. A key feature of the repaired in utero in 5 animals. A key feature of the repair method was the use of allogeneic bone paste made from fetal bone particles suspended in an agar-thickened modified Dulbecco's medium. The bone paste was used to correct the bone deficit produced by the laminectomy. All of the monkey babies were delivered by cesarean section at near term (160-164 days of gestation). Neurological test on the neonates and subsequent morphological studies indicated that the in utero treated animals developed normally. In contrast, 3 control animals, which had the induced spinal dysraphism but were left untreated, showed severe spina-bifida-like abnormalities, including paraplegia, incontinence and somatosensory loss.

Fetal surgery for neural tube defects

“…13 The model most closely approximating the human form, however, was that described in fetal lambs. 14 To mimic myelomeningocele, a laminectomy was performed exposing the spinal cord of the fetal lamb at 75 days of gestation, and the pregnancy was allowed to continue.…”

Validation of the ovine fetus as an experimental model for the human myelomeningocele defect

“…Postnatal treatment offers few possibilities for improvement in affected newborns, and prenatal treatment seems a reasonable alternative. There is evidence that the earlier the spinal cord can be enclosed, the smaller the degree of mechanical and chemical damage to it [1][2][3][4][5][6][7] . The surgical correction already performed in some human fetuses has also demonstrated the possibility of reversal of the posterior herniation of the cerebellum known as Type II Arnold-Chiari malformation [1][2][3] .…”

“…This herniation is responsible for the development of hydrocephalus, present in about 70% of myelomeningocele cases [1][2] . The possibility of improving the neurological condition with prenatal surgical correction of myelomeningocele was first demonstrated in an animal model (4)(5)(6) and the technique has been applied in humans since then [1][2] . However, this correction has used the "open surgery" approach, a very aggressive technique for both the mother and the fetus.…”

Estudo de uma nova técnica para criação cirúrgica de um defeito semelhante a meningomielocele em fetos de coelhos

“…A possibilidade de melhora do quadro neurológico com a correção cirúrgica pré-natal da meningomielocele, foi primeiramente demonstrada em modelo animal 4,5,6 e a correção vem sendo recentemente realizada em humanos 1,2 . Como resultado, o desenvolvimento de novas técnicas para a correção do defeito tornou-se um campo de pesquisa novo e importante.…”