DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for SAPHO syndrome — 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 moduleSAPHO syndrome 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 sapho syndrome 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
phosphodiesterase 9A (PDE9A) — PDE9A 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 1sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Y86 · 2.01 Å · ligand 6-{[(1S)-1-(4-chlorophenyl)ethyl]amino}-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (49D). Experimental structure, not a prediction.
What the evidence adds up to
SAPHO syndrome is rare and probably underrecognised. A 2016 single-centre cohort of 164 patients (111 women, 53 men; mean age 40.71 years) found that 143 had palmoplantar pustulosis and 25 had severe acne; 9 had osteoarticular symptoms without skin involvement. All 164 had anterior chest wall pain, 136 had peripheral joint involvement, and 111 had lumbosacral spine involvement. None had inflammatory bowel disease. C-reactive protein was elevated in 70.8% of patients; only 2.4% were HLA-B27 positive. No standard treatment exists. In that cohort, 79.9% took NSAIDs, 51.8% corticosteroids, 61% disease-modifying antirheumatic drugs, and 32.9% oral bisphosphonates.
A 2012 review states that current treatments are empirical and aim to relieve debilitating pain. NSAIDs and analgesics are first-line. Systemic corticosteroids, DMARDs, biologics targeting TNF-alpha and IL-1, and bisphosphonates have helped some patients but failed others. The review notes that bacteria and immunological dysfunction are hypothesised to play a role but remain poorly explored. A 2021 genome-wide association study of 49 patients and 121 controls found no single nucleotide polymorphism that reached genome-wide significance; pathway analysis suggested osteoclast differentiation and bacterial invasion of epithelial cells may be involved, but the study was small and no genetic variant was confirmed.
Two single-patient case reports describe responses to targeted therapies. In 2022, a 44-year-old man whose palmoplantar pustulosis did not respond to anti-inflammatory drugs and analgesics reported improvement in neck and thoracic back pain after two weeks of adalimumab, and palmoplantar pustules improved after four weeks. In 2024, a patient with accelerated disease progression who had not responded to traditional therapies received oral abrocitinib 100 mg daily; joint pain was completely relieved after 15 months, and no adverse events or recurrences were reported during 18 months of follow-up. Both reports are from single patients, not controlled trials.
What is still missing: no randomised controlled trials exist for any drug in SAPHO syndrome. The genetic study was underpowered to detect common variants. Patient stratification by skin phenotype, osteoarticular pattern, or biomarker status has not been attempted. Funding for multi-centre trials and systematic registries is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Arthritis and Rheumatism · 2012 · 300 citations · open access
The SAPHO Syndrome
AbstractOBJECTIVE: To review the epidemiology, presentation, diagnosis, treatment, pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of this entity. METHODS: We conducted a Medline search using SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and extracted further relevant articles from the retrieved references. RESULTS: The SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular disorders that are frequently accompanied by dermatoses characterized by neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is rare, although probably underrecognized because its diagnosis may be challenging because of the wide variability in its musculoskeletal and cutaneous manifestations. This is especially true when atypical sites are involved and when specific skin lesions are absent. There are no standardized treatment protocols available. Current treatments are empirical and have the objective of providing relief from the at times debilitating pain associated with SAPHO syndrome. They include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents. Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have all been beneficial in some patients, but ineffective in others. This suggests that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect remains poorly explored, although bacteria and immunological dysfunction are hypothesized to play a role. CONCLUSIONS: The early recognition, diagnosis, and prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term antibiotics or invasive procedures, while rapidly alleviating pain in a majority of affected patients.
Lara D. Veeken · 2016 · 83 citations · open access
Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients
AbstractOBJECTIVE: The aim was to assess the clinical, laboratory and radiological features of SAPHO syndrome. METHODS: We recruited all patients presenting to Peking Union Medical College Hospital from 2004 to 2015 diagnosed with SAPHO syndrome. The medical data, laboratory test results and imaging were collected for all patients. RESULTS: One hundred and sixty-four patients (111 women and 53 men) were recruited to our cohort. The mean age of the patients was 40.71 years. Nine patients had osteoarticular symptoms without skin involvement. One hundred and forty-three and 25 patients had palmoplantar pustulosis and severe acne, respectively. Psoriasis vulgaris was accompanied by palmoplantar pustulosis or severe acne in 24 patients. One hundred and sixty-four patients suffered from pain in the anterior chest wall, followed by spine (12 in the cervical region, 36 in the thoracic region and 111 in the lumbosacral region) and peripheral joint (136 patients) involvement. None of the patients had IBD. The hs-CRP level was increased in 70.8% patients. Only 2.4% were HLA-B27 positive. CT scan indicated osteolysis, sclerosis and hyperostosis in the anterior chest wall and spine in SAPHO syndrome patients. The bull-horn sign was the typical characteristic of SAPHO syndrome seen in bone scintigraphy images. One hundred and thirty-one (79.9%), 85 (51.8%), 100 (61%) and 54 (32.9%) patients took NSAIDs, CSs, DMARDs and oral bisphosphonates, respectively. CONCLUSION: SAPHO syndrome is predominant in middle-age women, characterized by dermatological and osteoarticular manifestations with unknown aetiology. CT scan and bone scintigraphy are useful for diagnosis. There is still no standard treatment to control the disease.
Frontiers in Cell and Developmental Biology · 2021 · 11 citations · open access
Genome-Wide Association Identifies Risk Pathways for SAPHO Syndrome
AbstractSAPHO syndrome is a rare chronic inflammatory disease which is characterized by the comprehensive manifestations of bone, joint, and skin. However, little is known about the pathogenesis of SAPHO syndrome. A genome-wide association study (GWAS) of 49 patients and 121 control subjects have primarily focused on identification of common genetic variants associated with SAPHO, the data were analyzed by classical multiple logistic regression. Later, GWAS findings were further validated using whole exome sequencing (WES) in 16 patients and 15 controls to identify potentially functional pathways involved in SAPHO pathogenesis. In general, 40588 SNPs in genomic regions were associated with P < 0.05 after filter process, only 9 SNPs meet the expected cut-off P -value, however, none of them had association with SAPHO syndrome based on published literatures. And then, 15 pathways were found involved in SAPHO pathogenesis, of them, 6 pathways including osteoclast differentiation, bacterial invasion of epithelial cells, et al. , had strong association with skin, osteoarticular manifestations of SAPHO or inflammatory reaction based published research. This study identified aberrant osteoclast differentiation and other pathways were involved in SAPHO syndrome. This finding may give insight into the understanding of pathogenic genes of SAPHO and provide the basis for SAPHO research and treatment.
AbstractRATIONALE: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is an autoinflammatory disease with no standardized treatment. Tripterygium wilfordii hook f (TwHF) is a Chinese herb with immunosuppressive effects and has been used to treat some chronic inflammatory diseases. However, it has not been reported as a therapeutic option in SAPHO syndrome. Here we present the first report in which a remarkable remission of SAPHO syndrome was achieved in response to TwHF. PATIENT CONCERNS: A 57-year-old female patient noted swelling and pain at the anterior chest wall and scattered rashes like psoriasis vulgaris. Bone scintigraphy demonstrated the classic "bull's head" sign and magnetic resonance images indicated bone marrow edema on T5. DIAGNOSES: The diagnosis was made by dermatological and osteoarticular manifestations and classical "bull's head" sign in bone scintigraphy. INTERVENTIONS: TwHF with a priming dose of 20 mg 3 times per day and a gradual dose reduction of 20 mg per day in every 3 months. Four months later, methotrexate was added with 10 mg per week. OUTCOMES: Osteoarticular symptoms and radiological abnormalities were improved dramatically. LESSONS: This case illustrates a promising strategy to treat SAPHO syndrome.
Clinical Cosmetic and Investigational Dermatology · 2022 · 7 citations · open access
SAPHO Syndrome with Palmoplantar Pustulosis as the First Manifestation Successfully Treated with Adalimumab
AbstractIntroduction: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is an acronym for synovitis, pustulosis, acne, hyperostosis, and osteitis, and clinically manifests as dermatological and musculoskeletal damage. Two major manifestations that co-occur in a single patient are rare. Methods/Results: This literature describes a 44-year-old male affected by SAPHO syndrome, whose first manifestation was palmoplantar pustulosis (PPP). Symptomatic treatments such as anti-inflammatory and analgesics did not work well for him. Adalimumab provided noteworthy improvement in the neck and thoracic back pain improvement after two weeks. The palmoplantar pustules were alleviated after four weeks. Conclusion: The literature on SAPHO syndrome therapy is increasing. Thus, adalimumab is a novel therapeutic agent. This report demonstrates the efficiency of adalimumab in SAPHO syndrome.
Journal of Dermatological Treatment · 2024 · 4 citations · open access
Successful treatment of SAPHO syndrome with oral abrocitinib: a case report
AbstractAIM: SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare autoimmune disorder characterized by typical cutaneous lesions (palmoplantar pustulosis and eruptive acne) and osteoarticular symptoms (aseptic osteomyelitis and joint inflammation). This study aims to evaluate the therapeutic efficacy and safety of Janus kinase 1 (JAK1) inhibitor abrocitinib in patients with SAPHO syndrome. METHODS: We presented a patient with SAPHO syndrome with accelerated disease progression who did not respond to traditional therapies. The patient was treated with oral abrocitinib at a dosage of 100 mg daily. RESULTS: After 3 months of treatment with abrocitinib, the patient exhibited considerable symptom improvement with no new facial lesions. The joint pain was completely relieved after abrocitinib administration for 15 months. No adverse events or recurrences were reported during the 18-month follow-up period. CONCLUSIONS: Abrocitinib monotherapy may be a promising treatment option for patients with SAPHO syndrome.
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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