DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for frozen shoulder — screening already-approved drugs against its 38-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFrozen shoulder maps to a 38-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 frozen shoulder 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
protein tyrosine phosphatase receptor type D (PTPRD) — PTPRD 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 flcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YD6 · 1.35 Å · ligand CITRATE ANION (FLC). Experimental structure, not a prediction.
What the evidence adds up to
In a 2019 study of 10 patients with idiopathic frozen shoulder and 10 controls, shoulder capsule samples showed increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of IL-6, IL-8 and CCL-20 compared with control fibroblasts. Exposing control fibroblasts to the inflammatory stimulus IL-1β significantly increased stromal activation marker transcript and protein expression for CD248, PDPN and VCAM. The authors concluded that fibroblasts have an activated phenotype in frozen shoulder and that this is associated with inflammatory cytokine dysregulation.
A 2017 review noted that the molecular biological mechanism for frozen shoulder remains unclear, and that research is focused on inflammation and cytokines associated with fibrosis. Repeated investigations have confirmed alterations of specified inflammatory mediators and fibrosis-associated cytokines, which might be involved in pathogenesis by causing structural changes and eventual movement limitation. The review aimed to provide a reference for subsequent research, treatment, and development of new drugs.
A 2019 systematic review of randomised clinical trials on non-surgical interventions for primary frozen shoulder included 30 trials. The majority of studies were evaluated as being at high risk of potential bias; only 4 trials were evaluated as low risk of bias. The variety of participants, methods, interventions and outcomes provided limited new evidence to inform non-surgical management. The review concluded that substantial evidence gaps remain for the non-surgical treatment of frozen shoulder.
A 2022 report stated that frozen shoulder has a prevalence of 2–5% in the general population, is most common in females and diabetic populations, and is essentially self-limiting, passing through freezing, frozen and thawing stages. It reported that up to 90% of patients recover with conservative measures. Patients with more severe initial symptoms, younger age at onset, and reduction in motion despite 4 months of therapy are most likely to require surgery. The author presented a ten-step technique for frozen shoulder release after failed conservative trial. What is still missing is a clear molecular target validated in larger patient samples, a low-risk-of-bias randomised trial comparing any specific drug intervention against placebo or standard care, and patient stratification that distinguishes the subset who will not recover with conservative measures from those who will.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2019 · 116 citations · open access
Fibroblast activation and inflammation in frozen shoulder
AbstractINTRODUCTION: Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the fibroblast compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder. METHODS: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Fibroblast activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1β upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR. RESULTS: Immunohistochemistry demonstrated increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM). CONCLUSIONS: These results show that fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease.
International Journal of Clinical Pharmacology and Therapeutics · 2018 · 43 citations
Platelet-rich plasma injection in the treatment of frozen shoulder: A randomized controlled trial with 6-month follow-up
AbstractPURPOSE: Platelet-rich plasma (PRP) has been utilized in the treatment of chronic injuries. The current study aimed to evaluate the efficiency of PRP in the treatment of frozen shoulder compared to procaine. MATERIALS AND METHODS: 60 patients with frozen shoulder were randomly divided into two groups. The PRP group was injected with 2 mL prepared PRP, while in the control group procaine was used. The stretching and formal strengthening exercises were carried out in both groups during the 6-month follow-up. Visual analog scale (VAS) score was used to assess the subjective pain intensity of the patients. The general shoulder assessment instruments (University of California at Los Angeles (UCLA) shoulder scale) was applied to measure the shoulder function of the patients. The evaluation was performed before treatment and 1 week, 1 month, 3 months, and 6 months after the first injection. RESULTS: The efficiency of PRP was superior to and longer than procaine. VAS scores were both declined in PRP and control group after 1 week, 1 month, and 3 months of first injection. By contrast, it was elevated was elevated in the control group while continued to decline in PRP group. The UCLA scores were almost linearly improved in the PRP group, while the UCLA scores decreased to a lower level at the final follow-up visit compared to that post 3 months in the control group. CONCLUSION: PRP and procaine were effective in treating frozen shoulder. PRP was more effective and had a more prolonged efficiency than the procaine control. Nevertheless, the definite conclusion should come from further large-scale clinical trials. .
Journal of Research in Medical Sciences · 2017 · 34 citations · open access
Molecular biology of frozen shoulder-induced limitation of shoulder joint movements
AbstractFrozen shoulder is a chronic condition characterized by pain in the shoulder and restriction of movements in all directions. Some patients are left with long-term limitation of shoulder joint activity with various severities, which results in reduced quality of life. Currently, there is a paucity of literature on the molecular biology of frozen shoulder, and the molecular biological mechanism for periarthritis-induced limitation of shoulder joint movements remains unclear. Research in this field is focused on inflammation and cytokines associated with fibrosis. Repeated investigations confirmed alterations of specified inflammatory mediators and fibrosis-associated cytokines, which might be involved in the pathogenesis of frozen shoulder by causing structural changes of the shoulder joint and eventually the limitation of shoulder movements. The aim of this article is to review studies on molecular biology of frozen shoulder and provide a reference for subsequent research, treatment, and development of new drugs.
Journal of Rehabilitation Medicine · 2019 · 29 citations · open access
Clinical effectiveness of non-surgical interventions for primary frozen shoulder: A systematic review
AbstractOBJECTIVE: To update an existing systematic review of randomized clinical trials evaluating the clinical effectiveness of non-surgical management interventions for people with primary frozen shoulder in terms of pain, movement, self-reported function and disability, quality of life, recovery time, return to work and recreation, and adverse events. DATA SOURCES: Cochrane CENTRAL, SCI and MEDLINE, CENTRAL between 1 January 2010 and June 2017, plus reference lists of included trials and trial registers. Abstracts were independently screened by 2 reviewers and discussed. DATA EXTRACTION: Two reviewers evaluated eligibility. Data were extracted by one reviewer and checked by another. Two reviewers evaluated risk of bias. Meta-analyses were not appropriate. Narrative analyses were performed for trials evaluated as low risk of bias. RESULTS: Thirty trials were included, with the majority of studies evaluated as being at high risk of potential bias. Only 4 trials were evaluated as being at low risk of bias and this, plus the variety of participants included/excluded in trials and the variety of methods, interventions and outcomes used across the trials provided limited new evidence to inform the non-surgical management and treatment of people with frozen shoulder. CONCLUSION: Substantial evidence gaps remain for the non-surgical treatment of people with frozen shoulder.
AbstractFrozen shoulder is a condition associated with painful restriction of shoulder joint movement. This condition has a prevalence of 2-5 % in general population, seen most often in females and diabetic population & is essentially a self limiting condition passing through stages of freezing, frozen & thawing. It has been reported that upto 90% patients recover with conservative measures. Patients with more severe initial symptoms, younger age at the time of onset, and reduction in motion despite 4 months of compliance with therapy are most likely to require surgery.Author presents ten step technique for frozen shoulder release in cases of failed conservative trial in management of frozen shoulder.
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.
