DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lymphopenia — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLymphopenia maps to a 7-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 lymphopenia 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
sphingosine-1-phosphate lyase 1 (SGPL1) — SGPL1 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 sindrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Q6R · 2.4 Å · ligand SUCCINIC ACID (SIN). Experimental structure, not a prediction.
What the evidence adds up to
In 413 nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy, a minimum absolute lymphocyte count below 390 cells/μL or a count below 705 cells/μL three months after treatment was significantly associated with worse overall survival, progression-free survival, and distant metastasis-free survival. Patients with both low minimum and low three-month counts had a hazard ratio for death of 3.79 (95% CI 1.75 to 8.19, p=0.001) compared to patients without lymphopenia. The three-month lymphocyte count was an independent prognostic factor for all three outcomes. In a separate study of 39 patients after spinal instrumentation surgery, lymphocyte percentage and number fell to 10% or less and 1,000/μL or less on postoperative day 1 in both infected and uninfected groups. In patients who developed wound infection, these parameters remained at those low levels until day 11, whereas in controls they began normalising by day 4. The authors concluded that lymphopenia represents immunodepression and increased susceptibility to infection.
In a retrospective cohort of 129 multiple sclerosis patients treated with siponimod, 121 (93.6%) reported lymphopenia events. Grade 4 lymphopenia occurred in 11 patients (8.5%), and grade ≤3 in 110 (85.3%). These rates were higher than those reported in the pivotal clinical trial (73.3% grade ≤3 and 3.3% grade 4). The study included an unexpectedly high proportion of male subjects (72.9%), which the authors note may have led to underestimation of the actual risk. In Crohn’s disease patients with persistent lymphopenia, the adjusted rate of myelotoxicity associated with immunosuppressant use was eight times higher (HR 8.2; 95% CI 3.4-19.9; p < 0.001). The same study reported that persistent lymphopenia was linked to a greater likelihood of requiring resective surgery.
No abstract in this set tests a drug intended to treat lymphopenia itself. The evidence describes lymphopenia as a prognostic marker of worse outcomes in cancer, a risk factor for postoperative infection, a common and often severe side-effect of siponimod in multiple sclerosis, and a predictor of myelotoxicity in Crohn’s disease patients on immunosuppressants. What is missing is any trial of a therapy that raises lymphocyte counts in these settings, and any prospective study that stratifies patients by baseline lymphocyte count before assigning treatment. The siponimod data come from a retrospective chart review with short follow-up and no control group; the Crohn’s disease finding is from an abstract with limited detail on sample size and selection. No funding for a dedicated lymphopenia treatment trial is 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.
Cancer Investigation · 2013 · 237 citations
Treatment-related Lymphopenia in Patients With Stage III Non-Small-Cell Lung Cancer
AbstractBACKGROUND: This study sought to estimate the severity, etiology, and clinical importance of treatment-related lymphopenia in patients with stage III non-small-cell lung cancer. METHODS: Serial lymphocyte counts and survival were analyzed retrospectively in 47 patients accounting for known prognostic factors. RESULTS: Total lymphocyte counts (TLCs) were normal before therapy and did not change following neoadjuvant chemotherapy. Following radiation, TLC fell by 67% (median 500 cells/mm(3), p <.00001). Multivariate analysis revealed an association between severe TLC and survival (HR 1.70, 95% CI: 0.8-3.6). CONCLUSIONS: Rapid and severe lymphopenia occurred in 50% of patients following radiation which was associated with reduced survival.
Cancer Research and Treatment · 2017 · 83 citations · open access
The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients
AbstractPURPOSE: This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. RESULTS: A minimum (mini)-absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ≥ 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ≥ 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ≥ 390 cells/μL and post3m-ALC ≥ 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006). CONCLUSION: Treatment-related lymphopenia was a poor prognostic factor in NPC patients.
Usefulness of White Blood Cell Differential for Early Diagnosis of Surgical Wound Infection Following Spinal Instrumentation Surgery
AbstractSTUDY DESIGN: The white blood cell (WBC) count and WBC differential were measured prospectively in patients after spinal instrumentation surgery with or without surgical wound infection. OBJECTIVES.: To investigate the usefulness of WBC differential for early diagnosis of surgical wound infection after spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: Renewed elevation of C-reactive protein (CRP) or WBC, gallium scan, and CRP/transthyretin mass concentration ratio were reported for early diagnosis of surgical wound infection. METHODS: A total of 39 patients were enrolled in this study: 13 patients who developed wound infection within 2 weeks after spinal instrumentation surgery (infection group) and 26 patients who were comparable with those patients included in the infection group with regard to age, sex, and surgical techniques used (control group). The WBC count and WBC differential were determined before and after surgery. RESULTS: In both groups, WBC and percentage and number of neutrophils showed nearly same change until postoperative 4 days (day 4). However, in the infection group, these parameters had increased after day 4. In both groups, the percentage and number of lymphocytes decreased to 10% or less and 1,000/microL or less on day 1, respectively. These lymphocyte parameters began to gradually normalize on day 4 and returned to the preoperative level 3 weeks after surgery in the control group. On the other hand, these parameters remained 10% or less and 1,000/muL or less until day 11 in the infection group. In patients with infection, the percentage and number of lymphocytes significantly decreased as early as on day 4. CONCLUSION: Lymphopenia represents immunodepression status, thus indicating the increased susceptibility to infection, which may lead to the development of postoperative infection. If lymphopenia is diagnosed as early as possible, surgical wound infection can be treated promptly without removing the instruments.
Journal of Clinical Medicine · 2023 · 4 citations · open access
The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study)
AbstractBACKGROUND: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. OBJECTIVE: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. METHODS: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. RESULTS: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade ≤ 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. CONCLUSIONS: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk.
Research Square · 2023 · 0 citations · open access
Title: The need for a closer monitoring of novel drugs in MS: a Siponimod retrospective cohort study (Realhes Study)
AbstractAbstract Background Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective To evaluate the incidence of lymphopenia during the first 3–6 months of siponimod treatment in clinical practice. Secondary objectives include analyses of factors predisposing to and the clinical relevance of lymphopenia events. Methods In this multicenter retrospective cohort study, collected information from the medical records of 129 patients with MS, from 15 tertiary hospitals in Spain, who initiated treatment with siponimod, were followed-up for at least 3 months and had at least one lymphocyte count evaluation. Results Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for Grade ≤ 3 and Grade 4 lymphopenia, respectively). Conclusion In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow up studies to properly characterize this risk. Trial registration EU PAS Register (http://encepp.eu), identifier #EUPAS45187 (January 17, 2022)
Journal of Crohn s and Colitis · 2016 · 0 citations · open access
P683. Skin lesions in patients with inflammatory bowel disease from southern Brazil: an epidemiologic study
AbstractPatients with persistent lymphopenia also had a significantly higher adjusted rate of myelotoxicity associated to the use of immunosuppressants (HR 8.2; 95% CI: 3.4-19.9; p < 0.001) Conclusions: Our results supported the existence of a lymphopenic phenotype in CD. CD patients with persistent lymphopenia are more likely to require resective surgery. The likelihood of developing myelotoxicity with immunosuppressive therapy was 8 times higher in patients with persistent lymphopenia. Therefore, treatment with immunosuppressive drugs in patients with persistent lymphopenia should be closely monitored
Journal of Crohn s and Colitis · 2016 · 0 citations · open access
P684. A shift to outpatient expenditures in healthcare costs for inflammatory bowel disease: a population-based study in Korea (2010–2014)
AbstractPatients with persistent lymphopenia also had a significantly higher adjusted rate of myelotoxicity associated to the use of immunosuppressants (HR 8.2; 95% CI: 3.4-19.9; p < 0.001) Conclusions: Our results supported the existence of a lymphopenic phenotype in CD. CD patients with persistent lymphopenia are more likely to require resective surgery. The likelihood of developing myelotoxicity with immunosuppressive therapy was 8 times higher in patients with persistent lymphopenia. Therefore, treatment with immunosuppressive drugs in patients with persistent lymphopenia should be closely monitored
Persisting lymphopenia and dimethyl fumarate: A clinical commentary
AbstractSevere prolonged lymphopenia as rare side-effect of dimethyl fumarate is mostly reversible. Caldito et al. report a case of persistent severe lymphopenia over 5 years after discontinuation of dimethyl fumarate. We discuss several clinical implications. Safe withdrawal of disease modifying therapies in terms of reoccurrence of disease activity and drug related adverse events need further attention as our treatment armamentarium continues to grow.
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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