DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spina bifida — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpina bifida maps to a 10-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for spina bifida is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) — LHPP is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet popdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2X4D · 1.92 Å · ligand PYROPHOSPHATE 2- (POP). Experimental structure, not a prediction.
What the evidence adds up to
Prenatal surgery for spina bifida, performed either by open fetal surgery with hysterotomy or by a minimally invasive fetoscopic approach, decreases the rate of ventriculoperitoneal shunt placement and improves motor function compared to standard postnatal surgery. Hindbrain herniation improves in more than 70% of cases, and the need for treatment for hydrocephalus falls to between 40% and 45% after either technique. Maternal obstetric outcomes are superior for the fetoscopic repair, which avoids the ongoing risk of uterine thinning or rupture that persists for every future pregnancy after open hysterotomy. The open fetoscopic approach, which requires laparotomy but is minimally invasive to the uterus, minimises the risk of ruptured membranes and subsequent preterm delivery compared with a completely percutaneous procedure. Vaginal delivery at term is possible after fetoscopic repair, and no scar complications have been reported so far. International collaboration is ongoing to assess long-term treatment effects.
In adults with spina bifida, intradetrusor injections of botulinum toxin A were studied retrospectively across 14 centres from 2002 to 2016. Among 561 injections, the global success rate — defined as resolution of urgency, urinary incontinence and detrusor overactivity or low bladder compliance — was significantly lower in patients with poor bladder compliance (34.4% versus 86.9%, odds ratio 0.08, p <0.001). On multivariate analysis, poor compliance remained associated with lower success (odds ratio 0.13, p <0.001). Female gender (odds ratio 3.53, p = 0.01) and older age (odds ratio 39.9, p <0.001) were predictors of global success. Complications occurred in 20 of 561 injections (3.6%), including three cases of muscular weakness. The authors conclude that botulinum toxin A is effective for detrusor overactivity but much less effective for poor bladder compliance.
Spina bifida is a neural tube defect characterised by incomplete closure of the spinal column, occurring mostly in the first trimester. Reported birth prevalence is about 0.4 per 1000 in developed countries, 0.7 per 1000 in the US, and 1.9 per 1000 in Asia. Myelomeningocele is the most common type. Non-genetic risk factors include anti-convulsant and anti-epileptic drugs, maternal obesity, maternal diabetes, and poor nutritional status (folate and vitamin B12 deficiency). Environmental factors include pesticides, nitrated compounds and air pollution. Common manifestations include Arnold Chiari II malformation, hydrocephalus, spinal cord abnormalities, latex allergy, breathing problems, urological abnormalities and cardio-metabolic dysfunction. For prevention, 0.4 mg of folic acid per day is recommended for mothers, rising to 4 mg per day in mothers with multiple pregnancies.
What remains missing is long-term follow-up data comparing fetoscopic and open fetal surgery for neurological and functional outcomes beyond infancy, and prospective trials to confirm the predictors of botulinum toxin A success in adults with spina bifida. No drug is proposed here as a treatment for the underlying defect; the interventions are surgical or symptomatic. The evidence for folic acid is preventive, not therapeutic after diagnosis. Funding for multicentre registries and randomised comparisons of fetoscopic techniques is needed, as is better stratification of adult patients by bladder compliance before botulinum toxin A is offered.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Minerva Obstetrics and Gynecology · 2019 · 21 citations
Fetoscopic spina bifida repair
AbstractINTRODUCTION: Spina bifida is the most common non-lethal congenital birth defect of the central nervous system that causes chronic disability due to the combined effects of local nerve damage and the sequelae of non-communicating hydrocephalus. This abnormality can be identified early in gestation and the damage can be progressive over the course of pregnancy. Advances in fetal treatment have made minimally invasive prenatal surgery a realistic consideration for spina bifida in order to improve the outcome for children affected this condition. EVIDENCE ACQUISITION: Prenatal surgery for spina bifida via open fetal surgery with hysterotomy decreases the rate of ventriculoperitoneal shunt placement and improves motor function compared to standard postnatal surgery. Maternal risks of open fetal surgery are primarily related to complications of the hysterotomy including thinning or rupture that begins in the index pregnancy but persists for every future pregnancy. Minimizing maternal risks is the largest impetus to explore and optimize a minimally invasive fetoscopic alternative. Techniques vary from using a complete percutaneous approach to open fetoscopy, which requires laparotomy but is minimally invasive to the uterus. This allows vaginal delivery at term and no scar complications are reported thus far. Fetal short-term neurosurgical outcomes compare favorably with improvement in hindbrain herniation >70% and decreased need for treatment for hydrocephalus between 40-45% after prenatal surgery performed either fetoscopically or through open fetal surgery. EVIDENCE SYNTHESIS: Maternal obstetric outcomes are superior for fetoscopic spina bifida repair compared to open fetal surgery and avoids the ongoing risk in future pregnancy. Neonatal and infant benefits appear equivalent. The open fetoscopic approach minimizes the risk of ruptured membranes and subsequent preterm delivery as opposed to a completely percutaneous procedure. International collaboration is ongoing to share experience and assess long term treatment effects. CONCLUSIONS: Continued refinement of a minimally invasive strategy for prenatal treatment of spina bifida is necessary to maximize benefits to the child and further minimize maternal risks and preterm birth.
Intradetrusor Injections of Botulinum Toxin A in Adults with Spinal Dysraphism
AbstractPURPOSE: The aim of the current study was to determine the outcomes of botulinum toxin A intradetrusor injections in adult patients with spina bifida. MATERIALS AND METHODS: All patients with spinal dysraphism who underwent intradetrusor injections of botulinum toxin A from 2002 to 2016 at a total of 14 centers were retrospectively included in analysis. The primary end point was the global success of injections, defined subjectively as the combination of urgency, urinary incontinence and detrusor overactivity/low bladder compliance resolution. Univariate and multivariate analysis was performed to seek predictors of global success. RESULTS: O, p = 0.002). A total of 20 complications (3.6%) were recorded for the 561 intradetrusor botulinum toxin A injections, including 3 muscular weakness complications. The global success rate of the first injection was significantly lower in patients with poor compliance (34.4% vs 86.9%, OR 0.08, p <0.001). On multivariate analysis poor compliance was associated with a lower global success rate (OR 0.13, p <0.001). Female gender (OR 3.53, p = 0.01) and patient age (OR 39.9, p <0.001) were predictors of global success. CONCLUSIONS: Intradetrusor botulinum toxin A injections were effective in adult patients with spina bifida who had detrusor overactivity. In contrast, effectiveness was much lower in adult patients with spina bifida who had poor bladder compliance. The other predictors of global success were female gender and older age.
AbstractIntroduction Review of Literature Clinical Material Analysis of Cases Cases in which Operation was not Performed Cases in which Operation was Performed Indications for Operation Method of Treatment Preoperative Care Operative Procedure Postoperative Care Follow-Up Results Comment Summary INTRODUCTION The problem of spina bifida has occupied the attention of surgeons for many years, and, in spite of a voluminous literature that has accumulated on the subject, fundamental differences of opinion still exist. Excellent contributions on the anatomy of spina bifida have been made by von Recklinghausen. 1 Keiller 2 and others; 3 however, the underlying factors in the pathogenesis of this condition have not been determined. Many theories have been advanced, but convincing proof of any of them is still lacking. One of us (E. S.) has always felt that hyperactivity of the choroid plexuses in utero before the neural arches have completely closed was a probable cause of the
The Professional Medical Journal · 2016 · 1 citations · open access
SPINA BIFIDA;
AbstractSpina Bifida (SB) is a neural tube defect (NTD) due defect in neural tube,characterized by incomplete closure of spinal column. Occurrence of SB varies in differentcountries. In developed countries, it is about 0.4 per 1000 births, in US 0.7 per 1000 births and inAsia 1.9 per 1000 births. SB mostly occurs during first trimester of pregnancy. Variants of SB areSpina bifida Occulata, Spina bifida Cystica [meningocele and myelomeningocele], Spina bifidaManifesta and Spina bifida Aperta. Among these myelomeningocele is the most common type.Causing agents of SB may be genetic, non-genetic or environmental factors. Non-genetic factorsinvolve anti-convulsant drugs, anti-epileptic drugs, maternal obesity, maternal diabetes andpoor nutritional status (folate and vitamin B12 deficiency). Environmental factors are pesticides,nitrated compounds and air pollution. Common manifestations are brain malformations (ArnoldChiari II malformation and hydrocephalus), spinal cord abnormalities, latex allergy, breathingproblems, urological abnormalities and cardio-metabolic dysfunction. Diagnostic techniquesfor Spina bifida are ultrasound screening, Magnetic Resonance Imagining (MRI), amniocentesisand maternal serum alpha-fetoprotein. To prevent the risk of Spina bifida, it is recommended forthe mother to use 0.4mg of folic acid per day or in mothers affected with multiple pregnanciesrecommended dose of folic acid is 4mg per day.
The Professional Medical Journal · 2016 · 1 citations · open access
SPINA BIFIDA; THE BASIC AND CLINICAL REVIEW
AbstractSpina Bifida (SB) is a neural tube defect (NTD) due defect in neural tube,characterized by incomplete closure of spinal column. Occurrence of SB varies in differentcountries. In developed countries, it is about 0.4 per 1000 births, in US 0.7 per 1000 births and inAsia 1.9 per 1000 births. SB mostly occurs during first trimester of pregnancy. Variants of SB areSpina bifida Occulata, Spina bifida Cystica [meningocele and myelomeningocele], Spina bifidaManifesta and Spina bifida Aperta. Among these myelomeningocele is the most common type.Causing agents of SB may be genetic, non-genetic or environmental factors. Non-genetic factorsinvolve anti-convulsant drugs, anti-epileptic drugs, maternal obesity, maternal diabetes andpoor nutritional status (folate and vitamin B12 deficiency). Environmental factors are pesticides,nitrated compounds and air pollution. Common manifestations are brain malformations (ArnoldChiari II malformation and hydrocephalus), spinal cord abnormalities, latex allergy, breathingproblems, urological abnormalities and cardio-metabolic dysfunction. Diagnostic techniquesfor Spina bifida are ultrasound screening, Magnetic Resonance Imagining (MRI), amniocentesisand maternal serum alpha-fetoprotein. To prevent the risk of Spina bifida, it is recommended forthe mother to use 0.4mg of folic acid per day or in mothers affected with multiple pregnanciesrecommended dose of folic acid is 4mg per day.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
