DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for mucolipidosis type IV — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMucolipidosis type IV maps to a 2-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 mucolipidosis type iv 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
mucolipin TRP cation channel 1 (MCOLN1) — MCOLN1 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 1s,2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7MGL · 2.9 Å · ligand N-{(1S,2S)-2-[4-(2-methoxyphenyl)piperazin-1-yl]cyclohexyl}benzenesulfonamide (ZB4). Experimental structure, not a prediction.
What the evidence adds up to
Mucolipidosis type IV is caused by mutations in the MCOLN1 gene, which encodes the lysosomal membrane protein mucolipin-1. A 2006 study showed that correcting the aberrant lactosylceramide trafficking seen in MLIV cells required both correct lysosomal localisation of mucolipin-1 and an intact ion pore; mistargeted protein or pore-region mutants did not rescue the defect. No therapy was tested in that experiment.
The natural history of MLIV, described in five patients from three Ashkenazi-Jewish families in a 1991 report, included hypotonia, developmental delay, corneal clouding, and puffy eyelids as presenting symptoms. Four patients had convergent strabismus, and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years; the oldest reached puberty at 20 years, developed a coarse face at 30, and was alive at 32. A 1979 review of five new cases and seven from the literature noted that the disease is not exclusive to Jewish people and that oligosacchariduria was absent in two cases.
Two abstracts concern the related disorders mucolipidosis II and III, not MLIV. A 1983 study found that both MLII and MLIII involve deficient N-acetylglucosamine-phosphate transferase activity, with genetic complementation analysis showing MLII is identical to one MLIII complementation group (ML IIIA). A 2019 study of three Brazilian patients with ML III gamma found that residual transferase activity appeared sufficient to maintain B-cell function, suggesting a less severe immune impairment than in MLII. These findings do not apply to MLIV.
No clinical trial data for any drug in MLIV were presented in these abstracts. What is missing is any evidence of a tested therapeutic intervention, any animal model drug study, and any patient stratification beyond the small natural-history series. Funding for preclinical drug screening and for trials that could measure meaningful endpoints in this ultra-rare disease remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Traffic · 2006 · 162 citations · open access
Mucolipin‐1 Is a Lysosomal Membrane Protein Required for Intracellular Lactosylceramide Traffic
AbstractMucolipin-1 is a membrane protein encoded by the gene MCOLN1, mutations in which result in the lysosomal storage disorder mucolipidosis type IV (MLIV). Efficient lysosomal targeting of mucolipin-1 requires di-leucine motifs in both the N-terminal and the C-terminal cytosolic tails. We have shown that aberrant lactosylceramide trafficking in MLIV cells may be rescued by wild-type mucolipin-1 expression but not by mucolipin-1 mistargeted to the plasma membrane or by lysosome-localized mucolipin-1 mutated in its predicted ion pore-selectivity region. Our data demonstrate that the correct localization of mucolipin-1 and the integrity of its ion pore are essential for its physiological function in the late endocytic pathway.
American Journal of Medical Genetics · 1991 · 69 citations
Mucolipidosis type IV: Clinical manifestations and natural history
AbstractThe clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.
Journal of Clinical Investigation · 1983 · 47 citations · open access
Mucolipidosis II and III. The genetic relationships between two disorders of lysosomal enzyme biosynthesis.
AbstractThe genetic relationships between the multiple variants of mucolipidosis II (I-cell disease) and mucolipidosis III (pseudo-Hurler polydystrophy) were investigated with a sensitive genetic complementation analysis procedure. These clinically distinct disorders have defects in the synthesis of a recognition marker necessary for the intracellular transport of acid hydrolases into lysosomes. Both disorders are associated with an inherited deficiency of a uridine diphosphate-N-acetyl-glucosamine: lysosomal enzyme precursor N-acetyl-glucosamine-phosphate transferase activity. We had previously shown that both disorders are genetically heterogeneous. Complementation analysis between mucolipidosis II and III fibroblasts indicated an identity of mucolipidosis II with one of the three mucolipidosis III complementation groups (ML IIIA), suggesting a close genetic relationship between these groups. The presence of several instances of complementation within this group suggested an intragenic complementation mechanism. Genetic complementation in heterokaryons resulted in increases in N-acetyl-glucosamine-phosphate transferase activity, as well as in the correction of lysosomal enzyme transport. This resulted in increases in the intracellular levels of several lysosomal enzymes and in the correction of the abnormal electrophoretic mobility pattern of intracellular beta-hexosaminidase. The findings demonstrate that a high degree of genetic heterogeneity exists within these disorders. N-acetyl-glucosamine-phosphate transferase is apparently a multicomponent enzyme with a key role in the biosynthesis and targeting of lysosomal enzymes.
AbstractFive new cases of Mucolipidosis IV are related and the seven cases in the literature reviewed. Neurological signs of the disorder and the value of skin and conjuncitival biopsies for its diagnosis are emphasized. Arguments in favour of a recessive autosomic inheritance are brought forth. The disease does not affect exclusively Jewish people. In two cases absence of oligosacchariduria was demonstrated.
Journal of Clinical Medicine · 2022 · 2 citations · open access
Anaesthesia-Relevant Disease Manifestations and Perianaesthetic Complications in Patients with Mucolipidosis—A Retrospective Analysis of 44 Anaesthetic Cases in 12 Patients
AbstractMucolipidosis (ML) type II, intermediate, and III are lysosomal storage disorders with progressive multiorgan manifestations predisposing patients to a high risk of perioperative morbidity. The aims of the study were to systematically assess disease manifestations relevant to anaesthesia as well as anaesthesia-related complications. This retrospective study includes ML patients who underwent anaesthesia in two centres between 2008 and 2022. We reviewed patients' demographics, medical history, disease manifestations, as well as procedure- and outcome-related data. A total of 12 patients (7 MLII, 2 ML intermediate, 3 MLIII) underwent 44 anaesthesia procedures (per patient: median 3, range 1-11). The median age was 3.3 years (range 0.1-19.1). At least one complication occurred in 27.3% of the anaesthesia procedures. The vast majority of complications (94%) occurred in children with MLII and ML intermediate. A predicted difficult airway was found in 100% and 80% of the MLII and ML intermediate patients, respectively. Accordingly, most complications (59%) occurred during the induction of anaesthesia. Altogether, respiratory complications were the most frequent (18%), followed by difficult airway management (14%). The risk for anaesthesia-related complications is alarmingly high in patients with ML, particularly in those with MLII and ML intermediate. Multidisciplinary risk-benefit analysis and thoughtful anaesthesia planning are crucial in these patients.
Humoral immune response in adult Brazilian patients with Mucolipidosis III gamma
AbstractAbstract Mucolipidosis II and III (ML II and III) alpha/beta and ML III gamma are lysosomal diseases caused by GlcNAc-1-phosphotransferase deficiency. Previous data indicate that MLII patients have functionally impaired immune system that contributes to predisposition to infections.We evaluated the immunological phenotype of three Brazilian patients with ML III gamma. Our data suggest that the residual activity of GlcNAc-1-phosphotransferase in patients with ML III gamma is enough to allow the targeting of the lysosomal enzymes required for B-cell functions maintenance.
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.
