DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for schizoaffective disorder — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSchizoaffective disorder maps to a 12-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
Structures already discussed alongside schizoaffective disorder in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
retinoid X receptor beta (RXRB) — RXRB is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has palmitic acid bound in it, shown as sticks.
Loading structure…
helix sheet plmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7A78 · 1.72 Å · ligand PALMITIC ACID (PLM). Experimental structure, not a prediction.
What the evidence adds up to
Paliperidone, both the extended-release oral formulation and the once-monthly injectable paliperidone palmitate, is approved in the United States for the treatment of schizoaffective disorder, the oral version since 2009 and the injectable after a completed relapse prevention study. Two pooled six-week, double-blind, placebo-controlled trials of paliperidone extended-release enrolled subjects aged 18–65 with an acute exacerbation of schizoaffective disorder; mean baseline Positive and Negative Syndrome Scale total score was 92.8 (SD 13.0), 79.5% had prominent manic symptoms, 66.9% prominent depressive symptoms, and 46.4% mixed symptoms. About 45% were taking adjunctive mood stabilisers or antidepressants. Paliperidone extended-release improved psychotic and mood symptoms in these subjects, whether used as monotherapy or with adjunctive medications. No new tolerability signals were reported; the most frequent adverse events across studies were mild extrapyramidal symptoms and increased serum prolactin.
For the injectable formulation, only one completed study was located as of 2015, and it demonstrated efficacy in preventing relapse. Three other studies were then recruiting. Efficacy and tolerability of paliperidone palmitate were similar to those of oral paliperidone in schizophrenia, and results were similar whether the drug was used alone or with adjunctive mood stabilisers or antidepressants. The injectable does not require initial co-administration of oral paliperidone, has relatively little risk of drug-drug interactions, and its pharmacokinetics allow once-monthly dosing, which is relevant for patients who may be non-adherent to daily oral regimens.
Separate from the paliperidone trials, a genetic study reported novel disease-specific mutations in the calreticulin gene core promoter and coding sequence in three unrelated cases of schizoaffective disorder out of 60 screened, with a contribution of 3.17% in that sample. These mutations were not found in 370 controls. This is the first instance of disease-specific mutations reported in schizoaffective disorder, but the finding comes from a small sample and has not been replicated in larger cohorts.
What remains missing are large, independently funded, long-term randomised trials that compare paliperidone formulations head-to-head against other antipsychotics or against placebo in well-characterised schizoaffective disorder populations, with stratification by mood episode type (manic, depressive, mixed) and by adherence patterns. No established treatment guidelines exist for schizoaffective disorder, and the diagnostic entity itself remains controversial. The genetic finding needs replication in much larger samples before it can inform patient selection.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology International · 2021 · 22 citations · open access
Paliperidone to Treat Psychotic Disorders
AbstractPurpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.
Neuropsychiatric Disease and Treatment · 2010 · 19 citations · open access
Role of paliperidone extended-release in treatment of schizoaffective disorder
AbstractSchizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18-65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response.
Neurology and Therapy · 2015 · 18 citations · open access
Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence
AbstractINTRODUCTION: Despite being frequently diagnosed, there has been very limited study of efficacious treatments for schizoaffective disorder. Paliperidone had been approved for the treatment of schizoaffective disorder, and a recently completed relapse prevention study of the use of a once-monthly injectable paliperidone formulation has also led to an indication for that preparation to treat schizoaffective disorder. METHODS: To review the efficacy and tolerability of paliperidone for schizoaffective disorder, we conducted a systematic literature search of studies of paliperidone in the treatment of schizoaffective disorder, and briefly reviewed evidence regarding the somewhat controversial nature of that diagnostic entity. RESULTS: We located several studies of the use of paliperidone extended release in the treatment of schizoaffective disorder, but only one completed study of the use of paliperidone palmitate, which demonstrated efficacy in preventing relapse. Three other studies are currently recruiting participants. Efficacy and tolerability were similar to the profile of oral paliperidone in the treatment of individuals with schizophrenia. These results were similar for both individuals treated with paliperidone palmitate alone, and for those treated with paliperidone palmitate with adjunctive mood stabilizers and/or antidepressants. The use of paliperidone palmitate does not require initial co-administration of oral paliperidone, has relatively little risk of drug-drug interactions, and its pharmacokinetics are favorable for once-monthly administration, an important treatment option for individuals with psychotic disorders, who may often be non-adherent to effective medication regimens. CONCLUSION: Paliperidone palmitate is an approved treatment for schizoaffective disorder, and can be efficacious with or without commonly employed adjunctive treatments.
Expert Opinion on Pharmacotherapy · 2010 · 15 citations
Paliperidone extended-release: a review of efficacy and tolerability in schizophrenia, schizoaffective disorder and bipolar mania
AbstractIMPORTANCE OF THE FIELD: Paliperidone extended-release (ER), a once-daily, oral, atypical antipsychotic, has been available in the USA and the EU for the treatment of schizophrenia for more than 2 years and was recently (July 2009) approved in the USA for treatment of schizoaffective disorder. Additional data on its efficacy and safety, including that for additional indications, is emerging. AREAS COVERED IN THIS REVIEW: This review provides a background on the compound and summarizes recent data available on treatment of schizophrenia, including comparative data with other antipsychotics, and efficacy and safety data from clinical trials in schizoaffective and bipolar disorders. WHAT THE READER WILL GAIN: The reader will gain knowledge of the compound and the existing clinical data so far for paliperidone ER. TAKE HOME MESSAGE: Paliperidone ER is effective for the treatment of schizophrenia and is at present the only antipsychotic approved in the USA for treatment of schizoaffective disorder. Its efficacy and tolerability profile in treating patients with schizophrenia or schizoaffective disorder indicates that paliperidone ER offers an important treatment option among atypical antipsychotic therapy for these patients.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics · 2009 · 12 citations
Novel mutations in the calreticulin gene core promoter and coding sequence in schizoaffective disorder
AbstractWe have recently reported the first case of mutation in the core promoter sequence of the human calreticulin gene in a family case of schizoaffective disorder. Remarkably, this gene coincides with a region of suggested linkage at 19p13.2, identified in a whole genome scan [Hamshere et al. (2005); Arch Gen Psychiatry 62;1081-1088]. The identified mutation was located at the conserved position -48 from the transcription start site, and was shown to be of functional effect, resulting in the aberrant expression of the gene. Following screening of the gene in 60 independent cases of schizoaffective disorder, we report novel germ-line mutations at positions -205 C > T and the conserved exon 5 (c: 682 C > T, pro228ser) in two unrelated cases of schizoaffective disorder. These mutations were disease-specific, and as for the -48 G > C mutation, neither was detected in a control population of 370 individuals, indicating a contribution of 3.17% in this sample series. To our knowledge, this is the first instance of disease-specific mutations in schizoaffective disorder, which warrants systematic screening of the regulatory and coding regions of the calreticulin gene in this disorder.
Efficacia, tollerabilità e sicurezza di paliperidone a rilascio prolungato nella terapia della schizofrenia e del disturbo schizoaffettivo
AbstractINTRODUCTION: The paper represents a systematic review on the efficacy, tolerability and safety of paliperidone, an antipsychotic drug recently approved in Italy for the treatment of schizophrenia and of schizoaffective disorder. METHODS: A comprehensive PubMed search using the term "paliperidone" was performed from January 1980 to February 2011. Papers reporting data on efficacy in the treatment of schizophrenia and of schizoaffective disorder were included, also if published as abstracts and all retrieved articles were manually searched for other references of interest. RESULTS: Paliperidone was found to be effective in short and long-term treatment of schizophrenia, as well as in the treatment of schizoaffective disorder. For both disorders, paliperidone showed to be effective in improving psychotic and affective symptoms. In the studies analyzed it was well tolerated and the most frequent reported adverse events were mild extrapyramidal symptoms and an increase in serum prolactin levels. CONCLUSIONS: Paliperidone has been shown to be an effective and safe medication for the treatment of schizophrenia and schizoaffective disorder. Further controlled clinical trials are needed to confirm this clinical profile in the long-term treatment, as well as for specific conditions such as schizophrenic patients with medical comorbidities.
The Journal of Clinical Psychiatry · 2010 · 5 citations
Individualizing Treatment for Patients With Schizoaffective Disorder
AbstractCompelling diagnostic definitions and evidence-based treatment recommendations for schizoaffective disorder are lacking, but clinicians can still develop an effective, individualized treatment regimen for patients with this condition. The steps necessary to help patients with schizoaffective disorder reach and maintain remission are to confirm the diagnosis, evaluate the patient's predictors of outcome, be aware of the available pharmacotherapeutic options and prescribe appropriate medications, and implement psychotherapy when patients achieve remission. In this brief activity, these essential steps are discussed and treatment recommendations are offered.
The Encyclopedia of Clinical Psychology · 2015 · 1 citations
Schizoaffective Disorder
AbstractAbstract Schizoaffective disorder is a serious and complex condition that includes symptoms of both schizophrenia and mood disorders. The complexity of schizoaffective disorder poses diagnostic challenges, but systematic study has yielded evidence regarding important clinical features, epidemiology, classification issues, and implications for 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.
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.
