DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lymphedema — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLymphedema maps to a 11-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 lymphedema 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
FKBP prolyl isomerase 1A (FKBP1A) — FKBP1A 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 4~{s},5~{r},6~{z},9~{s},10~{s},12~{e}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I1S · 1.52 Å · ligand (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione (E26). Experimental structure, not a prediction.
What the evidence adds up to
A 2004 pilot study gave 20 hyperbaric oxygen treatments (90 minutes at 2.0 ATA, five times a week for four weeks) to ten postmenopausal women with persistent arm lymphedema after breast cancer surgery and radiation. The average reduction in hand lymphedema was 38% (−7.4 ml, standard deviation 11.6, range −30 to +8 ml, p = 0.076, 95% confidence interval −15.7 to 0.9 ml) at the end of treatment. For the eight women who showed any reduction, it persisted to a final measurement an average of 14.2 months after the last treatment. However, total lymphedema volume of the whole arm did not change significantly. Vascular endothelial growth factor-C increased from baseline (p = 0.004) before treatment 20, suggesting the therapy had begun to stimulate that growth factor. The authors concluded that future studies should explore more treatments and more patients.
A 2013 imaging study adapted arterial spin labelling magnetic resonance to measure lymphatic flow non-invasively in six healthy subjects (mean age 30 years) and in three patients with stage II lymphedema plus three healthy controls with a cuff-induced lymphatic stenosis. Healthy lymphatic flow velocity from afferent vessel to axillary node was 0.61 cm/min ± 0.13. A significant reduction (p < 0.005) in flow velocity was seen in the affected arms of patients and in the arms of healthy subjects with the cuff. The ratio of unaffected to affected axilla lymphatic velocity in patients (1.24 ± 0.18) was significantly higher (p < 0.005) than the left-to-right ratio in healthy subjects (0.91 ± 0.18). The authors presented this as a foundation for future clinical investigations without exogenous agents.
A 2013 temporal data mining study of 232 breast cancer survivors identified higher body mass index and the presence of postoperative swelling as risk factors for developing secondary lymphedema. The analysis also found a difference in the trajectory of limb volume changes between patients who developed lymphedema quickly and those whose onset was delayed. The authors suggested the results could guide clinical guidelines for assessment of latent and early-onset lymphedema.
A 2021 review of secondary lymphedema pathogenesis described the sequence as lymphatic valvular insufficiency, obliteration or disruption of lymphatic vessels, and decreased lymphatic contractility, leading to lymphatic hypertension and lymph stasis. Accumulation of lymph, interstitial fluid, proteins, and glycosaminoglycans in skin and subcutaneous tissue eventually stimulates collagen production, disrupts elastic fibres, and activates keratinocytes, fibroblasts, and adipocytes, resulting in skin thickening and subcutaneous fibrosis. The review noted that the exact sequence of these mechanisms and their progression vary depending on the specific cause of lymphedema, and called for further studies to delineate the pathogenic processes surrounding the primary triggering event. What remains missing are adequately powered randomised trials of hyperbaric oxygen with sufficient treatment doses, validated non-invasive imaging biomarkers that correlate with clinical outcomes, and patient stratification by cause and stage of lymphedema to test tailored therapeutic approaches.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 2013 · 47 citations · open access
Clinical Feasibility of Noninvasive Visualization of Lymphatic Flow with Principles of Spin Labeling MR Imaging: Implications for Lymphedema Assessment
AbstractPURPOSE: To extend a commonly used noninvasive arterial spin labeling magnetic resonance (MR) imaging method for measuring blood flow to evaluate lymphatic flow. MATERIALS AND METHODS: All volunteers (n = 12) provided informed consent in accordance with institutional review board and HIPAA regulations. Quantitative relaxation time (T1 and T2) measurements were made in extracted human lymphatic fluid at 3.0 T. Guided by these parameters, an arterial spin labeling MR imaging approach was adapted to measure lymphatic flow (flow-alternating inversion-recovery lymphatic water labeling, 3 × 3 × 5 mm) in healthy subjects (n = 6; mean age, 30 years ± 1 [standard deviation]; recruitment duration, 2 months). Lymphatic flow velocity was quantified by performing spin labeling measurements as a function of postlabeling delay time and by measuring time to peak signal intensity in axillary lymph nodes. Clinical feasibility was evaluated in patients with stage II lymphedema (three women; age range, 43-64 years) and in control subjects with unilateral cuff-induced lymphatic stenosis (one woman, two men; age range, 31-35 years). RESULTS: Mean T1 and T2 relaxation times of lymphatic fluid at 3.0 T were 3100 msec ± 160 (range, 2930-3210 msec; median, 3200 msec) and 610 msec ± 12 (range, 598-618 msec; median, 610 msec), respectively. Healthy lymphatic flow (afferent vessel to axillary node) velocity was 0.61 cm/min ± 0.13 (n = 6). A reduction (P < .005) in lymphatic flow velocity in the affected arms of patients and the affected arms of healthy subjects with manipulated cuff-induced flow reduction was observed. The ratio of unaffected to affected axilla lymphatic velocity (1.24 ± 0.18) was significantly (P < .005) higher than the left-to-right ratio in healthy subjects (0.91 ± 0.18). CONCLUSION: This work provides a foundation for clinical investigations whereby lymphedema etiogenesis and therapies may be interrogated without exogenous agents and with clinically available imaging equipment. Online supplemental material is available for this article.
Can Hyperbaric Oxygen Therapy Reduce Breast Cancer Treatment-Related Lymphedema? A Pilot Study
AbstractOBJECTIVE: Arm lymphedema after surgery or radiation for breast cancer is common, causing pain and limitation of activities. Previous reports of hyperbaric oxygen (HBO) therapy for breast edema led us to consider the use of HBO therapy for arm lymphedema. METHODS: Ten healthy postmenopausal women (age 58 +/- 5.7 years) with persistent (9.4 years +/- 9.1 years) arm lymphedema following breast cancer surgery and radiation (n = 10) plus chemotherapy (n = 7) received 20 HBO treatments (90 minutes at 2.0 ATA five times a week for 4 weeks). End points included changes in upper extremity volume, platelet counts, plasma levels of vascular endothelial growth factor (VEGF), and lymph angiogenic-associated vascular endothelial growth factor-C (VEGF-C). Lymphedema volume (LV) was defined as the volume of the unaffected arm subtracted from the volume of the affected arm. RESULTS: We observed a 38% average reduction in hand lymphedema (-7.4 ml, 11.6 SD, range -30-+8 ml, p = 0.076, 95% confidence interval -15.7-0.9 ml) at the end of HBO, which was independent of changes in body weight. For those who benefited (n = 8), the reduction was persistent from the end of treatment to a final measurement an average of 14.2 months after the last HBO treatment. However, total LV did not change significantly. VEGF-C increased from baseline (p = 0.004) before treatment 20, suggesting HBO had begun to stimulate this growth factor. CONCLUSIONS: Future studies should explore the effects of a greater number of HBO treatments on lymphedema, with more patients.
Lymphatic Research and Biology · 2014 · 14 citations
Clinical Features of Docetaxel Chemotherapy-Related Lymphedema
AbstractLymphedema is a chronic, progressive, and multifactorial disease. The anticancer drug docetaxel (Taxotere) can lead to fluid retention, which is the main cause of peripheral edema of the extremities, pleural effusion, pericardial effusion, and ascites in patients undergoing chemotherapy. While there have been a few case reports documenting fluid retention-induced edema as a side effect of docetaxel, it is not yet clear whether docetaxel causes lymphedema directly. Here, we report cases of three patients who developed lymphedema after treatment with docetaxel.
Nursing Research · 2013 · 5 citations · open access
Using Temporal Mining to Examine the Development of Lymphedema in Breast Cancer Survivors
AbstractBACKGROUND: Secondary lymphedema is a lifetime risk for breast cancer survivors and can severely affect quality of life. Early detection and treatment are crucial for successful lymphedema management. Limb volume measurements can be utilized not only to diagnose lymphedema but also to track progression of limb volume changes before lymphedema, which has the potential to provide insight into the development of this condition. OBJECTIVES: This study aims to identify commonly occurring patterns in limb volume changes in breast cancer survivors before the development of lymphedema and to determine if there were differences in these patterns between certain patient subgroups. Furthermore, pattern differences were studied between patients who developed lymphedema quickly and those whose onset was delayed. METHODS: A temporal data mining technique was used to identify and compare common patterns in limb volume measurements in patient subgroups of study participants (n = 232). Patterns were filtered initially by support and confidence values, and then t tests were used to determine statistical significance of the remaining patterns. RESULTS: Higher body mass index and the presence of postoperative swelling are supported as risk factors for lymphedema. In addition, a difference in trajectory to the lymphedema state was observed. DISCUSSION: The results have potential to guide clinical guidelines for assessment of latent and early-onset lymphedema.
Journal of Skin and Sexually Transmitted Diseases · 2021 · 5 citations · open access
Secondary lymphedema: Pathogenesis
AbstractSecondary lymphedema follows an acquired defect in the lymphatic system. The common causes leading to a defective lymphatic function include infection, inflammation, malignancy, trauma, obesity, immobility, and therapeutic interventions. Understanding the pathogenesis of lymphedema is of prime importance in offering effective treatment. The pathogenetic mechanisms such as lymphatic valvular insufficiency, obliteration/ disruption of lymphatic vessels, and decreased lymphatic contractility aggravate lymphatic hypertension and lymphstasis. Accumulation of lymph, interstitial fluid, proteins, and glycosaminoglycans within the skin and subcutaneous tissue eventually stimulates collagen production by fibroblasts, causes disruption of elastic fibers, and activates keratinocytes, fibroblasts, and adipocytes. These result in thickening of skin and cause fibrosis of subcutaneous tissue. However, the sequence of these pathomechanisms, their inter-relationship and progression vary depending on the specific etiology of the lymphedema. In this article, we discuss the possible cellular and molecular mechanisms involved in the pathogenesis. Further studies to delineate the exact sequence of pathogenic processes surrounding the primary triggering event can help to formulate tailored therapeutic approaches.
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.
