DeCure for Immunodeficiency 114, folate-responsive
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 114, folate-responsive — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImmunodeficiency 114, folate-responsive maps to a 1-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 immunodeficiency 114, folate-responsive 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
solute carrier family 19 member 1 (SLC19A1) — SLC19A1 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 {[(6sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8HIJ · 3.54 Å · ligand N-[4-({[(6S)-2-AMINO-4-HYDROXY-5-METHYL-5,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID (THH). Experimental structure, not a prediction.
What the evidence adds up to
The 2013 report describes a single genetic form of severe combined immunodeficiency caused by compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional enzyme for processing single-carbon folate derivatives. The patient presented with SCID, megaloblastic anaemia, leukopenia, atypical haemolytic uremic syndrome, and neurologic abnormalities. Hydroxocobalamin and folate therapy provided only partial immune reconstitution. This is one case, and the therapy did not fully correct the immunodeficiency.
Two older abstracts address folate metabolism in HIV infection, not in the inherited immunodeficiency. A 1988 letter notes that in early HIV infection serum folate levels can be elevated, while cerebrospinal fluid folate levels can be low, and draws a parallel to the demyelination seen in vitamin B12 deficiency. A 1996 study of 29 HIV-positive patients used the deoxyuridine suppression test to assess vitamin B12 and folate status. Among 11 patients with low serum B12 or low red cell folate, only one showed a B12 deficiency pattern on the test, while the four with low red cell folate showed a folate deficiency pattern. The study also found that the drug azidothymidine (AZT) interfered with the test by reducing isotope incorporation, but did not entirely mask the deficiency pattern.
No abstract provides evidence that folate or B12 supplementation improves outcomes in HIV infection or in any immunodeficiency beyond the single MTHFD1 case. The 2013 case is the only one directly relevant to the disease name "immunodeficiency 114, folate-responsive," and even there the response was only partial. What is missing is any controlled trial of folate or B12 therapy in this or similar genetic immunodeficiencies, any data on patient stratification by mutation type, and any funding for systematic investigation of metabolic supplementation in rare inborn errors of immunity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PEDIATRICS · 2013 · 63 citations
Severe Combined Immunodeficiency Resulting From Mutations in <i>MTHFD1</i>
AbstractFolate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.
Abstract<h3>To the Editor.</h3> —The letter in the Jan 22/29 issue of<i>JAMA</i>entitled "Altered Folate Metabolism in Early HIV [human immunodeficiency virus] Infection"<sup>1</sup>is interesting, since the authors state that the elevated folate levels observed in the majority of their patients were unlikely to have resulted from dietary supplementation. A related letter entitled "Folate Deficiency and Demyelination in AIDS [acquired immunodeficiency syndrome]" by Smith et al<sup>2</sup>appeared in the July 25, 1987, issue of<i>Lancet</i>. The authors reported that, although serum and erythrocyte folate levels could be normal, cerebrospinal fluid folate levels were low. Defective folate metabolism is known to cause multifocal perivenular demyelination like that due to vitamin B12 deficiency. We would like to point out that in vitamin B<sub>12</sub>deficiency, serum folate levels, measured as 5-methyl tetrahydrofolate, are elevated because vitamin B<sub>12</sub>is needed for the demethylation of 5-methyl tetrahydrofolate; in its absence, no
European Journal Of Haematology · 1996 · 2 citations
The deoxyuridine suppression test in HIV‐1 positive patients: the role of azydothymidine (AZT)
AbstractThe deoxyuridine suppression test (dUST) was used to evaluate human immunodeficiency virus type 1 positive (HIV-1) patients with low serum levels of vitamin B12 and/or low red cell folate and to assess any possible interferences of azydothymidine (AZT) in this test. The dUST was studied in 29 HIV-1 positive patients, 18 without low serum vitamin B12 or low red cell folate and 11 with low serum vitamin B12 (6 patients), low red cell folate (4 patients) and 1 case with both. The role of AZT was studied using different concentrations (0.2, 2.5 and 10 microM/ml) in 2 groups: 1 group of 5 patients with vitamin B12 and/or folate deficiency and another group consisting of 13 healthy subjects. Methotrexate (MTX)(50 micrograms/ml) was added to induce a folate megaloblastic pattern in the latter group. Results of the dUST in the HIV-1 group without low levels of serum vitamin B12 fell within the health-related reference interval values. A vitamin B12 deficiency was only detected in 1 case in the HIV-1 group with low serum vitamin B12, although a folate deficiency pattern was observed in the 4 patients with low red cell folate. In the healthy subjects AZT induced a dose-dependent decrease of the MTX-induced folate megaloblastic pattern. The pattern was also observed in the group of patients with vitamin B12 or folate deficiency, although AZT did not entirely interfere with the dUST. The effect of AZT on the dUST was attributed to a decrease in the incorporation of the isotope in the absence of deoxyuridine. The dUST is useful in differentiating vitamin B12 deficient patients from HIV-1 infected patients with low levels of serum vitamin B12.
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.
