DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for lysosomal lipid storage disorder — 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 moduleLysosomal lipid storage disorder 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 lysosomal lipid storage disorder 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
tudor domain containing 1 (TDRD1) — TDRD1 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 2mrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5M9N · 1.95 Å · ligand N3, N4-DIMETHYLARGININE (2MR). Experimental structure, not a prediction.
What the evidence adds up to
Lysosomal storage disorders are a family of inherited diseases caused by mutations that disrupt lysosomal homeostasis, most often through deficiencies in lysosomal enzymes, leading to abnormal accumulation of macromolecular substrates. The term "cellular storage disorders" may be more appropriate, because pathways involving other membrane-bound organelles are also perturbed. In sphingolipid storage disorders, a subgroup, unmetabolised sphingolipids and glycosphingolipids accumulate, and these diseases are normally associated with devastating neurodegeneration and death at an early age. Despite years of study, little is known about the events that lead from lipid accumulation to pathology.
There is currently no definitive cure for lysosomal storage disorders. Although some therapies have been approved, their effectiveness is limited. Therapies must aim to correct storage not only morphologically but also reverse its pathobiochemical consequences, and because different disorders have different molecular causes, this requires custom tailoring. Liposomes have been proposed as drug carriers that could improve the efficacy of some therapies by offering protection, biocompatibility, and selectivity, but all promising liposomal formulations remain in preclinical development.
Diagnosis of suspected lipid storage disorders relies on measurement of specific enzymatic activities and molecular genetic studies. New approaches measuring lysosphingolipids may serve as rapid first-tier screening tests. In one 2024 study, lysosphingolipid elevation was detected in five patients with suspected lysosomal storage disease, and a definitive diagnosis was reached based on genetic analysis. The authors suggest these biomarkers may be used for diagnosis and treatment monitoring in the future.
What is still missing are therapies that can reverse the biochemical consequences of storage in a clinically meaningful way, not merely reduce morphological storage. No liposomal formulation has advanced beyond preclinical testing. No large, randomised trial has demonstrated that any lysosphingolipid biomarker strategy improves patient outcomes. Patient stratification by specific enzyme deficiency and disease subtype remains essential but is rarely addressed in trial design. Funding for these rare diseases is limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Cell Biology · 2012 · 693 citations · open access
Lysosomal storage disorders: The cellular impact of lysosomal dysfunction
AbstractLysosomal storage diseases (LSDs) are a family of disorders that result from inherited gene mutations that perturb lysosomal homeostasis. LSDs mainly stem from deficiencies in lysosomal enzymes, but also in some non-enzymatic lysosomal proteins, which lead to abnormal storage of macromolecular substrates. Valuable insights into lysosome functions have emerged from research into these diseases. In addition to primary lysosomal dysfunction, cellular pathways associated with other membrane-bound organelles are perturbed in these disorders. Through selective examples, we illustrate why the term "cellular storage disorders" may be a more appropriate description of these diseases and discuss therapies that can alleviate storage and restore normal cellular function.
Lysosomal storage disorders – challenges, concepts and avenues for therapy: beyond rare diseases
AbstractThe pivotal role of lysosomes in cellular processes is increasingly appreciated. An understanding of the balanced interplay between the activity of acidic hydrolases, lysosomal membrane proteins and cytosolic proteins is required. Lysosomal storage diseases (LSDs) are characterized by disturbances in this network and by intralysosomal accumulation of substrates, often only in certain cell types. Even though our knowledge of these diseases has increased and therapies have been established, many aspects of the molecular pathology of LSDs remain obscure. This Review aims to discuss how lysosomal storage affects functions linked to lysosomes, such as membrane repair, autophagy, exocytosis, lipid homeostasis, signalling cascades and cell viability. Therapies must aim to correct lysosomal storage not only morphologically, but reverse its (patho)biochemical consequences. As different LSDs have different molecular causes, this requires custom tailoring of therapies. We will discuss the major advantages and drawbacks of current and possible future therapies for LSDs. Study of the pathological molecular mechanisms underlying these 'experiments of nature' often yields information that is relevant for other conditions found in the general population. Therefore, more common diseases may profit from a correction of impaired lysosomal function.
Expert Opinion on Investigational Drugs · 2010 · 38 citations
Pharmacological small molecules for the treatment of lysosomal storage disorders
AbstractIMPORTANCE OF THE FIELD: Inherited lysosomal storage diseases often cause severe disability and have a devastating effect on quality of life. Enzyme replacement therapy (ERT) forms a cornerstone in the treatment of lysosomal enzyme deficiencies. Although for some lysosomal disorders ERT is lifesaving, important intrinsic restrictions of the approach are limited access of infused enzyme to less accessible body compartments such as the CNS, the burden of frequent intravenous administration, the emergence of antibodies and the high associated costs. Pharmacological small molecules may overcome these limitations. AREAS COVERED IN THIS REVIEW: Several novel therapeutic approaches using small molecules are emerging: substrate reduction therapy, pharmacological chaperone therapy, premature nonsense mutation suppressors and proteostasis regulators. WHAT THE READER WILL GAIN: Based on an extensive literature search up until June 2010, we here review the various therapeutic approaches with small compounds, including those currently in clinical use and those that have entered clinical trials. Compounds that are still in the preclinical phase are also briefly discussed. TAKE HOME MESSAGE: pharmacological small molecules are a new class of agents that show great promise for the treatment of lysosomal storage disorders.
Advanced Drug Delivery Reviews · 2022 · 24 citations · open access
Liposomal formulations for treating lysosomal storage disorders
AbstractLysosomal storage disorders (LSD) are a group of rare life-threatening diseases caused by a lysosomal dysfunction, usually due to the lack of a single enzyme required for the metabolism of macromolecules, which leads to a lysosomal accumulation of specific substrates, resulting in severe disease manifestations and early death. There is currently no definitive cure for LSD, and despite the approval of certain therapies, their effectiveness is limited. Therefore, an appropriate nanocarrier could help improve the efficacy of some of these therapies. Liposomes show excellent properties as drug carriers, because they can entrap active therapeutic compounds offering protection, biocompatibility, and selectivity. Here, we discuss the potential of liposomes for LSD treatment and conduct a detailed analysis of promising liposomal formulations still in the preclinical development stage from various perspectives, including treatment strategy, manufacturing, characterization, and future directions for implementing liposomal formulations for LSD.
Treatment of lysosomal storage disorders: Focus on the neuronal ceroid-lipofuscinoses
AbstractRecent advances in our understanding of lysosomal storage disorders (LSDs) may lead to new therapies to treat the neuronal ceroid-lipofuscinoses (NCLs). In this review, enzyme replacement therapy, gene therapy, cell-mediated therapy and pharmaceutical treatments are considered across the LSDs and extended to therapies for the NCLs. It is likely that a combination of approaches will produce the most beneficial clinical outcome for treatment of pathologies displayed by the NCLs.
Cellular pathogenesis in sphingolipid storage disorders: the quest for new therapeutic approaches
AbstractLysosomal storage disorders are caused by the defective activity of lysosomal proteins, which results in the lysosomal accumulation of undegraded metabolites. Sphingolipid storage disorders are a subgroup of lysosomal storage disorders, in which unmetabolized sphingolipids and glycosphingolipids accumulate. Sphingolipid storage disorders are normally associated with devastating neurodegeneration and death at an early age. Despite years of study of the genetic and molecular bases of sphingolipid storage disorders, little is known about the events that lead from lipid accumulation to pathology. Research over the past few years has demonstrated that sphingolipid storage can result in multiple direct or indirect effects on various cellular compartments and on biochemical pathways. This article offers a guided tour through the cellular scenes that may be of relevance to sphingolipid storage disorder pathogenesis and to the development of new therapeutic approaches.
Evaluation of Lysosphingolipid Analysis for the Diagnosis of Lysosomal Storage Disease
AbstractLysosomal storage disorders (LSD) are a group of inherited inborn metabolism errors that are characterized by a deficiency in the lysosomal enzyme. In patients with suspected lipid storage disorders, confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and molecular genetic studies. New approaches to the measurement of lysosphingolipids have been developed that may serve as a rapid first-tier screening tests for the evaluation of lysosomal storage disorders. The present study evaluates the results of lysosphingolipid screening tests in patients with suspected lysosomal storage diseases. Lysosphingolipid elevation was detected in five patients examined with suspected lysosomal storage disease, and a definitive diagnosis was reached based on genetic analysis. Our data support recent evidence of the primary role of LysoSLs in the diagnosis of sphingolipidosis, and suggest that these biomarkers may be used for diagnosis and treatment monitoring in the future.
Oxford University Press eBooks · 2016 · 0 citations
Lysosomal Storage Disorders
AbstractLysosomal storage disorders are characterized by the presence of nondegraded material in endosomal / lysosomal compartments. Any process that interferes with the lysosomal degradation or endosomal / lysosomal transport of molecules can give rise to storage. The cause may be genetic in nature or environmental, as is the case in drug-induced lipidoses or when undegradable materials are present. In this chapter we discuss the genetic lysosomal storage disorders.
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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