DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Niemann-Pick disease — screening already-approved drugs against its 4-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 maps to a 4-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
Structures already discussed alongside niemann-pick disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
acid-beta-glucosidase — Miglustat has a real, experimentally solved structure in complex with this target (PDB 2V3D, 1.96 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet nbvdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2V3D · 1.96 Å · ligand Miglustat (NBV). Experimental structure, not a prediction.
What the evidence adds up to
In a 2024 double-blind, placebo-controlled crossover trial, 60 patients aged 5 to 67 with genetically confirmed Niemann-Pick disease type C received N-acetyl-L-leucine (NALL) or placebo for two 12-week periods. The primary endpoint was the Scale for the Assessment and Rating of Ataxia (SARA) total score, where lower scores mean 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 were not adjusted for multiple comparisons. Adverse events were similar between groups, and no treatment-related serious adverse events occurred. The authors conclude that 12 weeks of NALL led to better neurologic status than placebo, but note that a longer period is needed to determine long-term effects.
Niemann-Pick disease type B is a multisystem disorder affecting pulmonary, cardiovascular, abdominal, and skeletal systems, and cross-sectional imaging can detect its various manifestations. A 2025 case report describes Niemann-Pick as a rare lysosomal storage disease divided into types A/B and C. Diagnosis of type A/B relies on enzymatic assay of acid sphingomyelinase; type C diagnosis uses plasma oxysterols as an initial screening test, confirmed by genetic testing. Differential diagnosis excludes other lysosomal diseases such as Gaucher and Wolman.
The 2024 trial provides the only controlled efficacy data for any drug in this disease class. The improvement on SARA was statistically significant but modest — less than 1.3 points on a 40-point scale — and the crossover design with short treatment periods cannot rule out carryover effects or assess durability. No data exist for NALL in Niemann-Pick types A or B, and no other drug trials are reported in these abstracts. What remains missing is a longer, parallel-group trial in type C, any trial in types A or B, and validated biomarkers or patient stratification that might identify who benefits most. Funding for such work is not described.
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.).
American Journal of Roentgenology · 2009 · 42 citations
Imaging Manifestations of Niemann-Pick Disease Type B
AbstractOBJECTIVE: The purpose of this article is to illustrate the various imaging manifestations of Niemann-Pick disease type B using various imaging techniques emphasizing cross-sectional imaging. CONCLUSION: Niemann-Pick disease type B is a multisystem disease that affects the pulmonary, cardiovascular, abdominal, and skeletal systems. Cross-sectional imaging is well suited for detecting and assessing the various manifestations of this disease, which can be highly suggestive of the diagnosis when seen in combination.
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).
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.
Disease-Modifying, Neuroprotective Effect of N-acetyl-L-leucine in Adult and Pediatric Patients with Niemann–Pick disease type C
AbstractAbstract Background The phase 3 randomized, placebo-controlled, crossover trial, IB1001-301, comparing N-acetyl-L-leucine (NALL) with placebo for the treatment of Niemann-Pick disease Type C (NPC) after 12 weeks met both its primary and secondary endpoints. In an open-label Extension Phase (EP) follow-up data have been obtained to evaluate the long-term effects of NALL for NPC. Here, we report on the safety and efficacy after 12 and 18 months of extended follow-up. Methods In the ongoing EP, pediatric and adult NPC patients received treatment with orally administered NALL 2-3 times per day in three tiers of weight-based dosing. The primary endpoint was the modified 5-domain Niemann-Pick disease type C Clinical Severity Scale (5-Domain NPC-CSS) (range 0-25 points; lower score representing better neurological status). Comparisons were made to the expected annual trajectory of decline (i.e. disease progression) on the 5-domain NPC-CSS established in published natural history studies. Analyses were also performed on exploratory endpoints including the 15-domain and 4-domain NPC-CSS and Scale for Assessment and Rating of Ataxia (SARA) scale. Results A total of 54 patients aged 5 to 67 years have been enrolled in the EP. After 12 months, the mean (SD) change from baseline on the 5-domain NPC-CSS was -0.32 (2.43) with NALL versus 1.5 (3.16) in the historical cohort (95% Confidence Interval, -3.11 to -0.53; p=0.007), corresponding to a 121% reduction in annual disease progression. After 18 months, the mean (SD) change was -0.067 (2.94) with NALL versus 2.25 (4.74) in the historical cohort (95% Confidence Interval, -4.17 to -0.46; p=0.017). The results of the 15-domain and 4-domain NPC-CSS were consistent with the primary analysis. The improvements in neurological signs and symptoms demonstrated in the Parent Study’s primary SARA endpoint were sustained over the long-term follow-up. NALL was well-tolerated, and no treatment-related serious AEs occurred. Conclusion In patients with NPC, treatment with NALL after 12 and 18 months was associated with a significant reduction in disease progression, demonstrating a disease-modifying, neuroprotective effect. Trial Registration Information The trial is registered with ClinicalTrials.gov ( NCT05163288 ; registered 06-Dec-2021), EudraCT (2021-005356-10). The first patient was enrolled into the EP on 08-Mar-2023.
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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