DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ganglioneuroma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGanglioneuroma maps to a 3-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 ganglioneuroma 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
myeloperoxidase (MPO) — MPO 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5MFA · 1.2 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
Ganglioneuroma is a benign tumour that can appear spontaneously or after treatment for neuroblastoma, and it may be metastatic or unresectable at the primary site. A 1989 review warned that the rarity of this condition and poor understanding of its biology can lead to extensive, potentially life-threatening attempts at surgical resection or the futile use of chemotherapy or radiotherapy to try to cause regression or control growth. A 2013 case report of a 42-year-old woman with a presacral ganglioneuroma noted that after counselling on nonoperative management the patient chose surgical resection, and the authors concluded that resection is reasonable given the tumour’s propensity for local effects and reported potential for malignant transformation. A 2022 post-mortem report described a two-year-old girl with diffuse intestinal ganglioneuromatosis affecting all gastrointestinal tract segments, a rare disease with high morbidity and mortality, and stressed the need for systematic investigation and genetic studies to rule out syndromic association.
A 2019 study of seven children with ganglioneuroma (median age 5.29 years) reported that complete resection was achieved in two patients and subtotal resection in four; histopathology confirmed ganglioneuroma in all six who underwent surgery. Over a median follow-up of 24 months, the two completely resected children had no recurrence, and the four with subtotal resection had no regrowth or malignancy. Among the four with residual tumour, one showed a thickened nerve in the sacral foramen on MRI, two had gradual shrinkage of residual tumour, and in one case the residual tumour gradually disappeared on ultrasound at 18 and 26 months. The authors concluded that if complete resection is difficult, leaving residual tumour may be acceptable because it can shrink spontaneously or even disappear after operation.
A 2020 preclinical study found high levels of phosphorylated AKT in 10 of 11 human ganglioneuroma samples but in only 1 of 15 poorly differentiated neuroblastoma samples (p<0.0001). Zebrafish transgenic for constitutively activated myr-Akt2 in the sympathetic nervous system developed ganglioneuroma without progression to neuroblastoma, and histopathology and transcriptome sequencing showed the zebrafish tumours closely resembled human ganglioneuroma. Inhibition of the downstream AKT target mTOR using sirolimus in these zebrafish effectively reduced tumour burden. The authors proposed a clinical trial of sirolimus to shrink large ganglioneuromas before resection and reduce surgical morbidity, but no such trial results are yet reported. What is still missing is a clinical trial in patients, adequate funding for such a trial, and any validated method to stratify patients by AKT pathway activation or other biomarkers that might predict response to mTOR inhibition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1989 · 121 citations · open access
Clinical manifestations of ganglioneuroma
AbstractGanglioneuroma may occur spontaneously or after therapy for neuroblastoma. This lesion may be metastatic or unresectable in the primary site. The rarity of this situation and lack of understanding of the biology of this benign condition may lead to extensive, potentially life-threatening attempts at surgical resection or the futile use of chemotherapy or radiotherapy to try to cause regression or control growth. The authors present here several cases which demonstrate the multiple presentations of ganglioneuroma and the potential problems which may arise in their management.
International Journal of Surgery Case Reports · 2013 · 18 citations · open access
Successful management of presacral ganglioneuroma
AbstractINTRODUCTION: Presacral ganglioneuromas are rare, usually benign lesions. Patients typically present when the mass is very large and becomes symptomatic. PRESENTATION OF CASE: This report describes the case of a 42 year old lady presenting with back pain who was subsequently diagnosed with a presacral ganglioneuroma based on MR imaging and a CT guided biopsy of the lesion. DISCUSSION: After counselling regarding nonoperative management, the patient opted for surgical resection. Open resection was performed with preservation of the neurovascular pelvic anatomy and an uneventful postoperative recovery. A review of the relevant literature was also performed using a search strategy in the online literature databases PUBMED and EMBASE. CONCLUSION: Surgical resection of a presacral ganglioneuroma is reasonable given their propensity for local effects and reported potential malignant transformation.
Boletín Médico del Hospital Infantil de México · 2022 · 1 citations · open access
Ganglioneuromatosis intestinal difusa a lo largo del tubo digestivo
AbstractBACKGROUND: Ganglioneuromas are histologically benign neoplasms derived from the sympathetic nervous system, whose occurrence in the gastrointestinal tract is rare and often syndromic. According to the injury pattern and extension, lesions are divided into polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. This work aimed to present the incidental post mortem finding of diffuse ganglioneuromatosis of the gastrointestinal tract in a patient without syndromic involvement. CASE REPORT: We describe the case of a two-year-old female patient with surgically corrected type III tracheoesophageal atresia and fistulous recanalization, multiple episodes of aspiration pneumonia, and septic shock. During the last admission, she developed massive pulmonary hemorrhage and multi-organ failure. Post mortem histopathological study identified hypertrophy of the pylorus and enlarged enteric nerve trunks and plexuses with intermingled mature ganglion cells. We identified ganglioneuromatosis affecting all gastrointestinal tract segments with the predominance of the myenteric plexuses. CONCLUSIONS: Intestinal ganglioneuromatosis is a rare disease with a spectrum of lesions ranging from isolated to syndromic with high morbidity and mortality. Therefore, it is necessary to know the condition, investigate systematically when it is suspected, and rely on genetic studies to confirm or rule out any syndromic association.
Postoperative changes of residual lesion in patients with ganglioneuroma
AbstractObjective
To explore the role of surgery for ganglioneuroma in children and observe the postoperative changes of residual lesion.
Methods
From January 2011 to December 2013, 7 patients with ganglioneuroma were recruited. There were 3 boys and 4 girls with an average age of 5.29 years. Imaging findings, operative findings, pathological examination and follow-up status were analyzed retrospectively.
Results
Imaging examinations confirmed neuroblastoma (n=3) and teratoma or liposarcoma (n=1). Among them, one gave up treatment after biopsy while the remainders were operated. Complete resection was achieved (n=2) while gross residue remained (n=4). Histopathological examination hinted at ganglioneuroma in all 6 patients. During a median follow-up period of 24 (6-36) months, 2 completely resected children had no recurrence and 4 with subtotal resection had no regrowth or malignancy. Among 4 with residual lesion, postoperative magnetic resonance imaging (MRI) demonstrated thickened nerve in sacral foramen (n=1); postoperative ultrasonography showed a gradual disappearing of residual tumor at 18 and 26 months, indicating no obvious residual signs; the sizes of residual tumors decreased gradually in another 2 cases.
Conclusions
Operation is not only an important diagnostic method, but also a sole treatment of ganglioneuroma. If complete resection is difficult, avoiding damaging organs and vessels may leave residual tumor postoperatively. Residual tumor may gradually shrink spontaneously or even completely disappear after operation.
Key words:
Ganglioneuroma; Neoplasm,residual; Follow-up studies
Abstract 3450: Ganglioneuromas are driven by activated AKT and can be therapeutically targeted with mTOR inhibitors
AbstractAbstract Peripheral sympathetic nervous system tumors are the most common extra-cranial pediatric tumors in children and include neuroblastoma, ganglioneuroblastoma (intermixed and nodular) and ganglioneuroma. The etiology and molecular pathogenesis of ganglioneuromas remains largely unknown. Surgery is the only effective therapy for ganglioneuroma, which can be challenging due to the location of the tumor and involvement of surrounding structures. Thus, there is need for well tolerated presurgical therapies that could reduce the size and extent of ganglioneuroma, and therefore limit surgical morbidity. Here we found high levels of phosphorylated AKT expressed in 10 of 11 patients with ganglioneuroma, but only in 1 of 15 who had poorly differentiated neuroblastoma (p&lt;0.0001, Fisher's exact test). Consistent with these results, zebrafish transgenic for constitutively activated myr-Akt2 in the sympathetic nervous system were found to develop ganglioneuroma without progression to neuroblastoma. Histopathological analysis and whole-transcriptome sequencing revealed that zebrafish ganglioneuroma highly resembles human ganglioneuroma. Inhibition of the downstream AKT target, mTOR, using sirolimus in zebrafish with ganglioneuroma effectively reduced the tumor burden, providing preclinical evidence for efficacy with this well tolerated drug. Our results implicate activated AKT as a tumorigenic driver in ganglioneuroma. We propose a clinical trial of sirolimus as a means to shrink large ganglioneuromas prior to resection in order to reduce surgical morbidity. Citation Format: Ting Tao, Hui Shi, Adam D. Durbin, Meng Wang, Antonio R. Perez-Atayde, Wendy B. London, Alejandro Gutierrez, Bernardo Lemos, A. Thomas Look. Ganglioneuromas are driven by activated AKT and can be therapeutically targeted with mTOR inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3450.
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.
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