DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Niemann-Pick disease, type C1 — 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 moduleNiemann-Pick disease, type C1 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 niemann-pick disease, type c1 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
NPC intracellular cholesterol transporter 2 (NPC2) — NPC2 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 c3sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KWY · 2.405 Å · ligand CHOLEST-5-EN-3-YL HYDROGEN SULFATE (C3S). Experimental structure, not a prediction.
What the evidence adds up to
A 2024 double-blind, placebo-controlled crossover trial randomly assigned 60 patients aged 5 to 67 years with genetically confirmed Niemann-Pick disease type C to receive N-acetyl-l-leucine (NALL) for 12 weeks then placebo for 12 weeks, or the reverse sequence. The primary endpoint was the Scale for the Assessment and Rating of Ataxia (SARA) total score, which runs from 0 to 40 with lower scores meaning better neurologic status. Mean baseline SARA scores were 15.88 before the first NALL dose and 15.68 before the first placebo dose. After 12 weeks, the mean change from baseline was –1.97 points on NALL and –0.60 points on placebo, a least-squares mean difference of –1.28 points (95% CI –1.91 to –0.65, p<0.001). Secondary endpoints generally supported the primary result, but those analyses were not adjusted for multiple comparisons. Adverse event rates were similar between arms, and no treatment-related serious adverse events occurred. The authors note that a longer period is needed to determine long-term effects.
Miglustat is the only disease-specific oral therapy approved for progressive neurological manifestations of Niemann-Pick disease type C, according to a 2017 review. A 2016 case report described a child with the severe infantile form who began miglustat at age 2 and then received intrathecal hydroxypropyl-β-cyclodextrin, starting at 175 mg and increasing to 325 mg every 15 days for 43 doses. A slight delay in disease progression was seen during the first year, but additional symptoms later emerged, suggesting a lack of effectiveness. The authors concluded the therapy was safe but its efficacy seemed questionable in that patient.
Diagnosis of Niemann-Pick disease type C remains challenging. A 2017 paper notes the broad clinical heterogeneity and variable age of onset; specific biochemical, histological, and molecular studies are required, and each approach has limitations that contribute to diagnostic delay. Approximately 95% of type C1 cases are caused by mutations in the NPC1 gene. A 2025 case report states that the biological diagnosis of type C relies on plasma oxysterols as an initial screening test, confirmed by genetic testing, and that differential diagnosis must exclude other lysosomal diseases such as Gaucher and Wolman.
What is still missing is long-term data on NALL beyond 12 weeks, a clear demonstration that any drug alters the course of the severe infantile form, and a diagnostic pathway that does not rely on multiple imperfect tests. No trial has yet stratified patients by age of onset or genetic subtype to see whether any treatment works better in a defined subgroup.
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 · 2024 · 101 citations · open access
Trial of <i>N</i> -Acetyl- <scp>l</scp> -Leucine in Niemann–Pick Disease Type C
AbstractBACKGROUND: -acetyl-l-leucine (NALL), an agent that potentially ameliorates lysosomal and metabolic dysfunction, for the treatment of Niemann-Pick disease type C. METHODS: In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. RESULTS: A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. CONCLUSIONS: Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).
Newborn presentation of Niemann–Pick disease type C – Difficulties and limitations of diagnostic methods
AbstractNiemann–Pick disease type C (NPC) is a neurodegenerative, lysosomal lipid storage disorder characterized by the accumulation of unesterified cholesterol and secondary lipids trafficking in lysosomes and late endosomes.1,2 The broad clinical heterogeneity and a variable age of onset make the diagnosis challenging, which is why specific biochemical, histological, and molecular studies are required in the diagnostic process.1,2 Each of the current approaches has its own limitations, contributing to a delay in the proper diagnosis.
European Journal of Hospital Pharmacy · 2016 · 5 citations · open access
Intrathecal cyclodextrin in the treatment of Niemann-Pick disease type C
AbstractCASE: A child with Niemann-Pick disease type C was started on miglustat therapy at the age of 2 years. Intrathecal administration of hydroxypropyl-β-cyclodextrin was added 5 months later. The initial dose of 175 mg was gradually increased over the first 6 months to reach 325 mg. The drug was administered every 15 days, and the patient received 43 doses. A slight delay in progression of the disease was seen during the first year of intrathecal hydroxypropyl-β-cyclodextrin. However, additional symptoms have emerged since that time, suggesting a lack of effectiveness of the drug. Our patient has shown no drug-related adverse events. CONCLUSIONS: Intrathecal hydroxypropyl-β-cyclodextrin therapy is safe, but its efficacy seems questionable in a patient with the severe infantile form of Niemann-Pick disease type C.
International Journal of Advances in Nursing Management · 2017 · 0 citations · open access
Niemann-Pick Disease: The Genetic condition and Nursing Consideration
AbstractNiemann-Pick Disease is one of a group of lysosomal storage diseases that affect metabolism and that are caused by genetic mutations. There are three most common types of disease namely Niemann-Pick Types A, B and C. Niemann-Pick disease type C is an inherited condition in which the body cannot properly metabolize cholesterol and fats, resulting in an excess of these substances in the body. Approximately 95% of Niemann-Pick type C cases are caused by Genetic mutations in the NPC1 gene, referred to as type C1. The most common symptoms are, hepatomegaly, splenomegaly, prolonged neonatal jaundice, ataxia, clumsiness or frequent falls, dysphagia, gelastic cataplexy, myoclonus and deafness. Miglustat is the only disease-specific oral therapy approved to treat progressive neurological manifestation of NP-C.
Cross Current International Journal of Medical and Biosciences · 2025 · 0 citations · open access
Rare Pathological Entity: Niemann Pick Disease in Adults, about a Case
AbstractNiemann Pick is a rare lysosomal storage metabolic disease. It is a sphingomyelin-cholesterol lipidosis associated with the accumulation of foamy cells, inherited in an autosomal recessive manner. It is divided into 3 main types (A/B, C). The biological diagnosis of type A/B relies on the enzymatic assay of acid sphingomyelinase, while that of type C is based on the search for plasma oxysterols which serves as the initial screening test, confirmed by genetic testing. The differential diagnosis consists of excluding other lysosomal diseases (Gaucher, Wolman).
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.
