DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for severe congenital neutropenia — screening already-approved drugs against its 16-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSevere congenital neutropenia maps to a 16-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 severe congenital neutropenia 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
WASP actin nucleation promoting factor (WAS) — WAS 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2A3Z · 2.078 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
A 1968 study of 15 patients with severe absolute neutropenia lasting one to 19 years found no bone-marrow hypoplasia or splenomegaly, no increase in infection frequency, and no progression to leukaemia or lupus. The neutropenia did not respond to corticosteroids, and the authors concluded that this benign condition requires no therapy. This stands in sharp contrast to severe congenital neutropenia, which later reviews describe as a rare condition that, without treatment, can cause fatal complications.
By 2006 and 2007, reviews noted that severe congenital neutropenia comprises several genetically distinct entities. Mutations in the neutrophil elastase gene ELA2 were identified in 1999 in cyclic, sporadic and autosomal dominant neutropenia. Homozygous mutations in the antiapoptotic gene HAX1 were later found in autosomal recessive severe congenital neutropenia. Other syndromal forms involve mutations in lysosome-related proteins and are associated with lymphoid immunodeficiency and pigmentation defects such as Chédiak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2, or deficiency of the endosomal adaptor p14. Ongoing linkage studies suggested that more genes remained unidentified.
A 2015 review stated that patients with acute febrile neutropenia should be treated with antibiotics, and that patients at high risk of severe neutropenia (greater than 20% risk) after myelosuppressive chemotherapy should receive prophylactic myeloid growth factor, usually granulocyte colony-stimulating factor (G-CSF). For severe chronic neutropenia, the same review gave specific recommendations for treatment with G-CSF. A separate 2015 review on paediatric neutropenia noted that acquired neutropenia is usually benign, while congenital neutropenia is rare and can cause fatal complications without pathogenic therapy.
What is still missing are prospective trials that stratify patients by the specific genetic mutations now known to cause severe congenital neutropenia, and that test whether G-CSF or other interventions alter the natural history in each genetic subgroup. The long-term risks of G-CSF therapy in these patients, including leukaemic transformation, remain inadequately quantified. Funding for such stratified trials and for registries that track outcomes by genotype is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1968 · 101 citations
Chronic Idiopathic Neutropenia
AbstractIn a study of 15 patients with severe absolute neutropenia of one to 19 years' duration there was no bone-marrow hypoplasia or splenomegaly, and the cause of the neutropenia was not apparent. These patients had no increase in the frequency of infections, and leukemia, lupus erythematosus and other serious disease did not develop. The neutropenia was chronic and did not respond to corticosteroids. This benign condition does not require therapy and should be recognized as such.
Current Opinion in Hematology · 2015 · 81 citations · open access
How I diagnose and treat neutropenia
AbstractPURPOSE OF REVIEW: Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). RECENT FINDINGS: Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated. SUMMARY: The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.
Archives of Disease in Childhood · 2006 · 53 citations · open access
The investigation and management of chronic neutropenia in children
AbstractUnravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered.
Current Opinion in Rheumatology · 2007 · 29 citations
Severe congenital neutropenia: new genes explain an old disease
AbstractPURPOSE OF REVIEW: This review summarizes the recent advances in the diagnosis and molecular characterization of isolated and syndromal forms of severe congenital neutropenia. RECENT FINDINGS: It has become evident that severe congenital neutropenia comprises several genetically distinct entities. In 1999, mutations were identified in the neutrophil elastase gene ELA2. ELA2 mutations have been found in cyclic, sporadic and autosomal dominant neutropenia. Recently, homozygous mutations in the antiapoptotic gene HAX1 were found in patients with autosomal recessive severe congenital neutropenia. Ongoing linkage studies suggest that more and, as yet unidentified, genes may be involved in the pathophysiology of severe congenital neutropenia. In other patients, congenital neutropenia is not an isolated finding but is associated with other abnormalities, in particular, lymphoid immunodeficiency and pigmentation defects such as Chédiak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2, or deficiency of the endosomal adaptor p14. The molecular identification of these disorders originating from mutations in lysosome (related) proteins has advanced our knowledge of intracellular protein trafficking. SUMMARY: Recent insights into the molecular etiology of severe congenital neutropenia provide the opportunity for a definitive genetic classification system. Based on this knowledge, disease-related risks may be recognized and optimized therapeutic options may become available.
Neutropenia in pediatric hematology/oncology practice
AbstractAcquired neutropenia is one of the most common conditions in pediatric hematology practice. These conditions usually are benign. In contrast, congenital neutropenia are rare conditions, but in the absence of pathogenic therapy can cause fatal complications. Approach to the differential diagnosis and management of these patients are discussed in this review.
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.
