DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cystinosis — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCystinosis maps to a 1-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 cystinosis 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
cystinosin, lysosomal cystine transporter (CTNS) — CTNS 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 iyydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8DKM · 3.39 Å · ligand L-cystine (IYY). Experimental structure, not a prediction.
What the evidence adds up to
In a 1993 case series of 36 adult nephropathic cystinosis patients referred to the US National Institutes of Health, seven were dead, five with functioning allografts. One-year and five-year graft survival for 30 cadaveric allografts were 90% and 75%. Mean height and weight were severely retarded. Five patients were legally blind, three others had severely impaired vision in one eye. Thirty-one of 36 required thyroid hormone replacement. One third had distal myopathy, 21 had moderate to severe swallowing abnormalities, and eight had cerebral calcifications on CT scan. Only 11 patients were receiving adequate cystine-depleting therapy with cysteamine or phosphocysteamine.
A 2015 French retrospective analysis of 31 renal transplants in 30 adult cystinosis patients between 1980 and 2013 reported median age at transplantation of 20.4 years. Compared to a matched control cohort of 93 patients, graft survival was better in cystinosis patients (p = 0.013). Multivariate analysis gave a hazard ratio of 0.11 (95% CI 0.02–0.61) for graft loss. During follow-up, four patients developed diabetes mellitus, one hypothyroidism, one liver involvement, and two neurologic involvement. Post-transplant diabetes occurred in 4 of 31 cystinosis patients (13%) versus 5 of 93 controls (5%), a difference that was not statistically significant (p = 0.25).
A 2022 case-control study from Kuwait compared 17 paediatric cystinosis renal transplant recipients with 126 matched controls. Mean age was 12.4 years in the cystinosis group. Patients with cystinosis received significantly more potent induction therapy, but maintenance immunosuppression was comparable between groups. The percentage with primary graft function was significantly higher in the cystinosis group (p = 0.024), though baseline creatinine was not significantly different. Post-transplant complications including diabetes, cytomegalovirus viraemia, and BK nephropathy were comparable. Patient and graft survival rates were similar between groups.
A 2024 case report describes a Japanese patient with intermediate cystinosis, a form accounting for about 5% of cases. Urinary abnormalities were detected at age 3, cystinosis was diagnosed at age 12, and cysteamine therapy was started. Over 10 years of treatment, renal function progressed slowly. Two renal biopsies showed multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis. The authors note that intermediate cystinosis can be difficult to diagnose due to its rarity and variable presentation, and that few patients tolerate cysteamine because of side effects and complicated administration schedules. What remains missing are prospective trials with sufficient sample size to determine optimal immunosuppression and cysteamine dosing in cystinosis transplant recipients, particularly for the intermediate form, and studies that stratify patients by age at diagnosis, genotype, and adherence to cystine-depleting therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA · 1993 · 99 citations
Classic Nephropathic Cystinosis as an Adult Disease
AbstractOBJECTIVE: To delineate the clinical characteristics of infantile nephropathic cystinosis in adult patients who have undergone renal transplantation. DESIGN: Case series. SETTING: Clinical research unit. PATIENTS: All 36 adult patients with nephropathic cystinosis referred to the National Institutes of Health. OUTCOME MEASURES: Longevity, growth, renal allograft survival, visual acuity, endocrine insufficiency, myopathy and swallowing dysfunction, cerebral calcifications, and occupational status. RESULTS: Of the 36 patients, seven were dead, five with functioning allografts. The 1-year and 5-year graft survival rates for 30 cadaveric allografts were 90% and 75%, respectively. The patients' mean height and weight were severely retarded. Five patients were legally blind, and three others had severely impaired vision in one eye. Thirty-one (86%) of 36 patients required thyroid hormone replacement therapy. One third had a distal myopathy, and 21 had moderate to severe swallowing abnormalities. Eight patients had cerebral calcifications on computed tomographic scan. Despite these complications, the sighted patients engaged in a normal variety of occupations. Only 11 patients were receiving adequate cystine-depleting therapy with cysteamine (mercaptamine) or phosphocysteamine. CONCLUSIONS: Adult patients with nephropathic cystinosis suffer serious complications of the disease.
Orphanet Journal of Rare Diseases · 2015 · 41 citations · open access
Excellent long-term outcome of renal transplantation in cystinosis patients
AbstractBACKGROUND: Cystinosis is a rare lysosomal disorder leading to end stage renal disease in more than 90 % of patients before 20 years of age. Data about safety and efficiency of renal transplantation in patients with cystinosis is scarce. We evaluated long-term outcomes of renal transplantation in adult patients with cystinosis. METHODS: Data of renal transplantation (n = 31) in 30 adult patients with cystinosis in 5 French university transplant centers between 1980 and 2013 were retrospectively analyzed. A control cohort of 93 patients was matched for age, graft date, living/deceased donor status and transplant center. RESULTS: Median age at transplantation was 20.4 years (7-36.5). At transplantation, all patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had hypothyroidism. Graft survival was better in patients with cystinosis than in control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95 [0.02-0.61]). Specific complications of cystinosis occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus (PTDM) was not statistically different in cystinosis group compared to control group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no differences regarding calcineurin inhibitors and steroids treatments during follow-up. CONCLUSIONS: Renal transplantation appears to be safe with excellent long-term outcomes in patients with cystinosis. These patients may receive standard immunosuppressive regimens with steroids and calcineurin inhibitors.
Experimental and Clinical Transplantation · 2022 · 2 citations
Cystinosis in Pediatric Renal Transplant Recipients: A Case-Control Study From Kuwait
AbstractOBJECTIVES: Cystinosis is the most frequent cause of the inherited renal Fanconi syndrome and is also potentially treatable. In this study, we have reported our single-center experience of the longterm outcomes of kidney transplant in patients with cystinosis. MATERIALS AND METHODS: Pediatric patients with cystinosis (n = 17) were compared with a matched control group without cystinosis (n = 126). The 2 groups were compared with regard to demographic data, posttransplant complications, and graft and patient outcomes. RESULTS: Most patients with cystinosis were male teenagers (52.9%) with comparable mean age (12.4 ± 4.1 vs 14 ± 3.1 years) versus the group without cystinosis. The 2 study groups were comparable with regard to type of dialysis, type of donor, blood group, and pretransplant comorbidities (P > .05). Patients with cystinosis received significantly more potent induction therapy (P < 0.05), but both groups were maintained on comparable immunosuppressive regimens (mostly tacrolimus based) (P > .05). Most grafts in both groups displayed immediate graft function. The percentage of patients with cystinosis with primary graft function was significantly higher than the percentage of those patients without cystinosis who had primary graft function (P = .024); this was associated with a relatively lower baseline creatinine level, although this was not significant (P > .05). Posttransplant complications, especially posttransplant diabetes, cytomegalovirus viremia, or BK nephropathy, were comparable (P > .05). Moreover, patient and graft survival rates were similar in the 2 groups (P > .05). CONCLUSIONS: Under standard immunosuppression, renal transplant and cysteamine therapy were safe with good long-term outcomes in patients with cystinosis. Studies that can include more patients and that have longer follow-up are needed to better understand the nature of this genetic disease and to discover the best treatment options.
Intermediate cystinosis: a case report of 10-year treatment with cysteamine
AbstractBACKGROUND: Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years. CASE PRESENTATION: Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient's renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient's renal function remained stable. CONCLUSIONS: This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment.
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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