DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Niemann-Pick disease type A — 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 moduleNiemann-Pick disease type A 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 niemann-pick disease type a 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
sphingomyelin phosphodiesterase 1 (SMPD1) — SMPD1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I81 · 2.25 Å · ligand none (apo structure). 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 years with Niemann-Pick disease type C received N-acetyl-l-leucine (NALL) or placebo for 12 weeks each. The mean change in the Scale for the Assessment and Rating of Ataxia (SARA) total score was -1.97 points after NALL and -0.60 after placebo, a difference of -1.28 points (95% CI -1.91 to -0.65, p<0.001). Secondary end points were generally supportive, but the trial was not adjusted for multiple comparisons. Adverse events were similar between groups, and no treatment-related serious adverse events occurred. The authors note that a longer period is needed to determine long-term effects.
Niemann-Pick disease is a rare lysosomal storage disorder inherited in an autosomal recessive manner. Type A/B is diagnosed by enzymatic assay of acid sphingomyelinase; type C by plasma oxysterol screening confirmed by genetic testing, with approximately 95% of type C cases caused by mutations in the NPC1 gene. Miglustat is the only disease-specific oral therapy approved for progressive neurological manifestations of NP-C. A 2017 case report describes a 35-year-old woman with an intermediate form of Niemann-Pick type B who presented with psychotic symptoms; treatment with ziprasidone, quetiapine, and valproic acid improved her psychotic symptoms and autonomy, though the authors note such psychiatric presentations are uncommon.
Earlier literature describes the natural history of the disease. A 1932 report notes that Niemann-Pick disease typically starts in infancy around 5 or 6 months, with retarded physical and mental development, enlarged liver and spleen, brownish skin discolorations, and death usually before age 2 from respiratory infection. A 1972 case of a childhood variant (Crocker Group B) describes unique chromogenic bodies in foamy histiocytes and suggests that dissolution of these bodies might correlate with a benign course. A 2009 review notes that type B is a multisystem disease affecting pulmonary, cardiovascular, abdominal, and skeletal systems, with cross-sectional imaging useful for detection. A 2025 synthesis paper reports that a hydroxy-15-azasterol, a cholesterol mimic that binds NPC1 and NPC2 proteins, was completed in 12 steps from 2-oxepanone, but no clinical data are provided.
What is still missing are long-term data on NALL beyond 12 weeks, any trial of the azasterol in patients, and a clear understanding of which patient subgroups (by genotype, age, or disease severity) might benefit most. No treatment has been shown to alter the underlying disease course in type A or B, and psychiatric manifestations remain poorly characterised and managed.
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.
Archives of Otolaryngology - Head and Neck Surgery · 1932 · 10 citations
PATHOLOGIC CHANGES IN THE EAR IN NIEMANN-PICK'S DISEASE
AbstractBefore describing the pathologic changes in the ear in a case of Niemann-Pick's disease, it is perhaps advisable first to say a word or two about the disease itself. For a more comprehensive study on the subject the reader is referred to the excellent papers by Pick,<sup>1</sup>Niemann,<sup>2</sup>Bloom,<sup>3</sup>Kramer<sup>4</sup>and others. In brief, Niemann-Pick's disease is a condition that starts in infancy, usually at the age of 5 or 6 months. The child has a retarded physical and mental development; the abdomen is enlarged, owing to the increased size of the liver and spleen, and brownish discolorations of the skin are present. The disease is occasionally associated with amaurotic family idiocy and mongolism. A low grade fever, anemia and cachexia are present. The child succumbs to the disease, usually from associated infection of the upper respiratory tract, before the age of 2 years. A
American Journal of Clinical Pathology · 1972 · 2 citations
Childhood Variant of Niemann-Pick Disease: Report of a Case with Biochemical, Histochemical, and Electron Microscopic Observations
AbstractMiller, William L., ancl Reimann, Bernhard E. F.: Childhood variant of Niemann-Pick disease: Report of a case with biochemical, histochemical, and electron microscopic observations. Am. J. Clin. Pathol. 58: 450–457, 1972. Studies of a young child with Niemann-Pick disease (Crocker Group B category) revealed the presence of unique, chromogenic bodies occurring in association with the foamy histiocytes of the tissues. The bodies were readily observable in and outside of cells at the light microscopic level, and electron microscopy showed them to be analogous in structure to the smaller, previously described, cytosomal inclusions of the Niemann-Pick cell. Serial examination of all intracellular structures showed a distinctive pattern of morphologic origin, progression of development, and ultimate dissolution within the histiocyte as a final sequence. As the intracellular aspect of these bodies appeared to have a limited life, it is postulated that this dissolution capability could perhaps correlate with the patient’s benign course thus far.
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.
A CASE OF NIEMMAN-PICKu2019S DISEASE IN PSYCHIATRY
AbstractBackground and Aims:The patient with Niemann-Pick disease type B usually presents with hepatosplenomegaly, pathologic alterations on lungs, pancytopenia, caused by splenomegaly, sometimes there are eye abnormalities (cherry-red spot), neurological symptoms, most often mental retardation, peripheral neuropathy and seizures, bones also may be affected.Methods:A 35-year-old woman is hospitalized in a psychiatric clinic. About a month before hospitalization, she became tense, psychomotor agitated, with lively speech, mentally torn, unable to cope with her daily activities. She has psychotic symptoms since the age of 17. Till now she was treated in different psychiatric departments for affective and psychotic symptoms. In 2015 she was diagnosed with Niemann-Pick Type B disease u2013 an intermediate form, because of neurological symptoms that she has .Results:After reviewing the medical history our team decided to start treating the patient with Ziprasidone 40 mg/daily, Quetiapine 100 mg/daily and Valproic acid 1000 mg/daily. Diagnosis was defined as Organic Mood Disorder. At the first week of the treatment we observed improvement in psychotic symptoms. Gradually there was a reduction in the psychomotor agitation, she aligned mentally, despite of discrete flight of ideas, perceptual disturbances were decasualized. The patient became notably autonomous to self-care and move independently. Conclusions:Although the psychotic symptoms of Niemann-Pick type B disease - intermediate form are uncommon, in the case presented, they determine the poor quality of life and lead to a more severe course of the disease.
AbstractNiemann-Pick type C (NPC) is a lysosomal storage disorder that will cause eventual brain damage with limited treatment options available. Though clinical trials are undergoing with repurposed pharmaceuticals, no novel chemotype exists purely for the treatment of NPC. In 2021, an azasterol was found to bind to both NPC1 and NPC2 proteins and is considered as a cholesterol mimic. A convergent synthesis to obtain a hydroxy-15-azasterol was completed in 12 steps, from 2-oxepanone.
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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