DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for lysosomal storage disease — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLysosomal storage disease maps to a 45-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 storage disease 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
ganglioside GM2 activator (GM2A) — GM2A 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 7rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2AG4 · 1.8 Å · ligand (7R)-4,7-DIHYDROXY-N,N,N-TRIMETHYL-10-OXO-3,5,9-TRIOXA-4-PHOSPHAHEPTACOSAN-1-AMINIUM 4-OXIDE (LP3). Experimental structure, not a prediction.
What the evidence adds up to
Lysosomal storage diseases are a family of inherited disorders caused by gene mutations that disrupt lysosomal homeostasis, mainly through deficiencies in lysosomal enzymes or non-enzymatic proteins, leading to abnormal storage of macromolecular substrates. The term "cellular storage disorders" may be more appropriate because cellular pathways associated with other membrane-bound organelles are also perturbed. Therapies exist that can alleviate storage and restore normal cellular function, but the presently available treatments are not able to address all clinical manifestations of these multisystemic disorders and do not cure the patient.
Enzyme replacement therapy accounts for the vast majority of approved therapies for lysosomal storage diseases, but a number of challenges facing these existing therapies have become very obvious. New drugs under development are divided into enzyme-targeted and substrate-targeted groups. Enzyme-targeted drugs include substances that modify the enzyme to make it more accessible to organs such as bone or brain, enhance enzyme activity via chaperones, or activate enzyme synthesis by inducing read-through of premature stop codons. Substrate-targeted drugs inhibit the synthesis or modify the structure of the substrate, through substrate deprivation or substrate optimization. The potential for new drugs is vast, as a high number of lysosomal storage diseases have no available therapy, and alternative approaches for diseases with existing treatment are much needed.
The interest of scientists and pharmaceutical companies in lysosomal storage diseases has increased dramatically, leading to a rising number of different drugs that act at several stages of the pathophysiological cascade. However, the increasing number of these very expensive drugs may lead to significant consequences for the health economic system. As the complexity of the diseases becomes increasingly revealed, novel therapeutic targets continuously nurture the development of new candidate drugs, but the presently available treatments are unable to address all clinical aspects of these multifaceted diseases. Future therapy will most likely consist of combinations of established and emerging approaches, as the complexity of the diseases demands a certain degree of humbleness to the expectations for a cure based on a single therapy.
What is still missing are therapies that can address all clinical manifestations of these disorders, particularly for the many lysosomal storage diseases that currently have no available treatment. The field lacks a cure, and it will still take a long time until new drugs are developed that are capable of curing patients. The development of effective therapies is hampered by the need to address the multisystemic nature of these diseases, and the challenge of delivering drugs to organs such as the brain. No concrete numbers for survival or response rates are reported in these reviews, and no specific drug names are mentioned.
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.
Expert Opinion on Emerging Drugs · 2010 · 42 citations
Emerging drugs for lysosomal storage diseases
AbstractIMPORTANCE OF THE FIELD: Because orphan drug regulations encouraged development of drugs for rare disorders by granting marketing exclusivity for many years and other commercial benefits, treatment has become achievable for a few lysosomal storage disorders also. The presently available therapies, however, are not able to address all aspects of these multisystemic disorders and do not cure the patient. Therefore, there is a need for producing new drugs that are based on known pathophysiological mechanisms, such as enzyme replacement or inhibition of substrate synthesis, or which use new approaches to prevent the build-up of storage material. AREAS COVERED IN THIS REVIEW: New compounds that are being designed by different pharmaceutical companies can be divided in two groups, enzyme targeted and substrate targeted drugs. Enzyme targeted drugs include substances that modify the enzyme to make it more accessible to organs such as the bone or the brain, enhance enzyme activity (chaperones) or activate enzyme synthesis by small molecules that induce read-through of premature stop codons of genes that bear a nonsense mutation. To the group of substrate targeted drugs belong substances that inhibit the synthesis or modify the structure of the substrate (substrate deprivation or substrate optimization, respectively). For this review, a literature research has been undertaken that covers the years 1968 - 2010. WHAT THE READER WILL GAIN: The reader of this paper will get an overview of drugs for lysosomal storage disorders that are on the market or are under development. This will help in the understanding of the pathophysiological mechanisms that underlie these rare metabolic diseases. In addition, the reader should realize that the increasing number of these very expensive drugs may lead to significant consequences for the health economic system. TAKE HOME MESSAGE: In the last years, the interest of scientists and pharmaceutical companies in lysosomal storage disorders has increased dramatically, leading to the production of a rising number of different drugs. These drugs act at several stages of the pathophysiological cascade, for example, at the level of the substrate (substrate deprivation) or of the enzyme (enzyme enhancement). The presently available treatments are not able to address all clinical manifestations of these disorders, and it will still take a long time until new drugs are developed that are capable of curing the patients.
Expert Opinion on Orphan Drugs · 2013 · 34 citations
Emerging therapies and therapeutic concepts for lysosomal storage diseases
AbstractIntroduction: The success of the first enzyme replacement therapy (ERT) for a lysosomal storage disease (LSD) and the regulatory and commercial incentives provided by authorities for orphan and rare diseases has spawned a massive interest for developing drugs for these intriguing but devastating genetic disorders. The potential for new drugs in this arena is vast, as not only a high number of LSDs have no available therapy, but also alternative therapeutic approaches for diseases with existing treatment are much needed as a number of challenges facing the existing therapies have become very obvious. A significant unmet medical need is therefore apparent for most, if not all of the LSDs and the development of new therapies based on the increasing knowledge of the pathophysiological mechanisms involved in these devastating diseases is therefore anticipated with great interest from all stakeholders. Areas covered: The reader will be introduced to the intricate biological processes involved in lysosomal regulation and how these are exploited for current and emerging therapies. Therapies utilizing these processes will be thoroughly reviewed with regard to their mechanism of action, their clinical status and the challenges they are faced with and/or are aiming to address. For this review, a literature research has been undertaken that covers the years 1955 – 2012. Expert opinion: The interest in lysosomal biology and disease has surged over the past decade not only in the halls of science but also of pharmaceutical companies. As the complexity of the LSDs increasingly become revealed, so do novel therapeutic targets continuously nurturing the development of new candidate drugs for these devastating diseases. Among this multitude of approaches, the ERTs still account for the vast majority of approved therapies but a number of exciting alternative approaches are emerging targeting various components of the pathophysiological cascade. This evolution of the field is much needed as the presently available treatments are unable to address all clinical aspects of these multifaceted diseases. Future therapy will most likely consist of combinations of these established and emerging approaches as well as other yet to be discovered concepts as the complexity of the diseases demands a certain degree of humbleness to the expectations for a cure based on a single therapy.
Current Opinion in Rheumatology · 2008 · 17 citations
Lysosomal storage diseases as differential diagnoses to rheumatic disorders
AbstractPURPOSE OF REVIEW: To describe the latest findings on lysosomal storage diseases relevant to rheumatologists, including literature findings on the natural history, clinical features, diagnostic measures, and treatment. RECENT FINDINGS: Many relevant investigations are based on large lysosomal storage disease registries. The steadily growing number of patients has resulted in an increasingly accurate description of the natural history of the diseases and permits the investigation of special problems, including monitoring the long-term safety and effectiveness of treatment. For Gaucher disease, several semi-quantitative and quantitative techniques have been proposed to measure bone marrow involvement and thus to monitor the effectiveness of enzyme replacement therapy. Given the unspecific symptoms of Fabry disease during childhood, several studies highlight the importance of a thoroughly recorded family history in making the correct diagnosis. Two investigations describe the specific features of Fabry disease in women. SUMMARY: Given the rheumatologist's awareness of lysosomal storage diseases, the latest findings on the natural history of lysosomal storage diseases allow earlier diagnosis and treatment. The results of enzyme replacement therapy are promising, but large studies with control groups carried out over a longer period of time are lacking.
Journal of Veterinary and Animal Sciences · 2021 · 1 citations · open access
Lysosomal storage diseases
AbstractLysosomes play a pivotal role in cellular processes through an active interplay of enzymes, lysosomal membrane proteins, and cytosolic proteins. Lysosomal storage diseases are a group of inherited and acquired disorders. Clinically affected animals are presented with developmental and neurological symptoms. This review aims to discuss the function of lysosomes, the pathogenesis of lysosomal storage disease, and its diagnosis.
Oxford University Press eBooks · 2013 · 1 citations
Inherited metabolic diseases
AbstractA variety of hereditary disorders can present with structural or functional alterations of the musculoskeletal system. In particular, genetic defects within enzymatic pathways involved in the lysosomal degradation of various substrates can manifest with bone or joint symptoms. Because musculoskeletal complaints are frequently the first reason for the patient to seek medical advice, the rheumatologist may play a crucial role in the early diagnosis of these diseases. Lysosomal storage diseases are a heterogeneous group of individually very rare disorders, but taken together they have a prevalence of more than 1 in 8000 live births. Some of these lysosomal storage diseases can nowadays be treated very effectively by enzyme replacement therapies; however, a timely start of treatment is essential to avoid irreversible organ damage and deterioration of the quality of life. Therefore, the rheumatologist should be able to recognize signs and symptoms of the most frequent treatable lysosomal storage diseases.
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.
