DeCure for Inclusion body myopathy and brain white matter abnormalities
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for inclusion body myopathy and brain white matter abnormalities — 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 moduleInclusion body myopathy and brain white matter abnormalities 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 inclusion body myopathy and brain white matter abnormalities 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.
What the evidence adds up to
In 1988, five of six male siblings from one family developed a progressive myopathy beginning in early childhood. Muscle biopsies in all five showed the characteristic changes of inclusion body myositis. CT and MRI revealed markedly abnormal cerebral white matter in the four affected patients who were tested, but clinical and laboratory examinations found no evidence of central white matter dysfunction. Muscle biopsies and brain imaging were normal in all clinically unaffected family members. The authors concluded that this constellation represented a previously undescribed syndrome.
A 2002 review of sporadic inclusion-body myositis and hereditary inclusion body myopathies proposed that overexpression of amyloid-beta precursor protein within aging muscle fibres is an early upstream event. The review listed several processes thought to be important: increased transcription and accumulation of amyloid-beta precursor protein and its proteolytic fragment Abeta; accumulations of phosphorylated tau and other Alzheimer-related proteins; accumulation of cholesterol and low-density lipoprotein receptors, possibly due to abnormal cholesterol trafficking; oxidative stress; and a milieu of muscle cellular aging. The review discussed unfolded or misfolded proteins as a possible mechanism in inclusion body formation. It noted remarkable pathologic similarities between s-IBM muscle and Alzheimer disease brain.
A 2014 study identified ten children with NMDA receptor antibodies and white matter disorders from 46 consecutive NMDAR antibody-positive paediatric patients. Three distinct clinicoradiologic phenotypes were recognised: brainstem encephalitis (n=3), leukoencephalopathy following herpes simplex virus encephalitis (n=2), and acquired demyelination syndromes (n=5); three of the five with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Six of the seven patients (85%) who were treated acutely during the original presentation with white matter involvement improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titres. The authors concluded that white matter involvement was identified in 22% of children with NMDAR antibodies and appeared immunotherapy responsive, particularly when treated in the acute phase.
No study has yet tested any drug specifically for the syndrome of inclusion body myopathy with brain white matter abnormalities. The 1988 report described only a single family, with no treatment data. The 2002 review discussed pathogenesis but offered no clinical trial results. The 2014 study involved a different disease (NMDAR antibody-associated white matter syndromes) and a different patient population (children), not the adult-onset myopathy with leukoencephalopathy seen in the 1988 family. What is missing is any prospective trial, any animal model of the combined syndrome, any biomarker to stratify patients, and any funding for a condition so rare that it may have been described in only one family.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
NMDA receptor antibodies associated with distinct white matter syndromes
AbstractOBJECTIVE: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. METHOD: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody-positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. RESULTS: THREE DISTINCT CLINICORADIOLOGIC PHENOTYPES WERE RECOGNIZED: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. CONCLUSION: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease.
Current Opinion in Neurology · 2002 · 95 citations
Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms
AbstractPURPOSE OF REVIEW: Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion body myopathies are progressive muscle diseases that lead to severe disability. We discuss recent advances in illuminating their pathogenic mechanism(s). RECENT FINDINGS: We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. Our basic hypothesis is that over-expression of amyloid-beta precursor protein within aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis: (a) increased transcription and accumulation of amyloid-beta precursor protein, and accumulation of its proteolytic fragment Abeta; (b) accumulations of phosphorylated tau and other Alzheimer-related proteins; (c) accumulation of cholesterol and low-density lipoprotein receptors, the cholesterol accumulation possibly due to its abnormal trafficking; (d) oxidative stress; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss unfolded and/or misfolded proteins as a possible mechanism in formation of the inclusion bodies and their consequences. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease brain are discussed. SUMMARY: Unfolding knowledge of the various pathogenetic aspects of the s-IBMs and hereditary inclusion body myopathies may lead to new therapeutic avenues.
FAMILIAL MYOPATHY WITH CHANGES RESEMBLING INCLUSION BODY MYOSITIS AND PERIVENTRICULAR LEUCOENCEPHALOPATHY
AbstractFive of 6 male siblings were affected by a progressive myopathy beginning in early childhood. Muscle biopsies in all patients showed the characteristic changes of inclusion body myositis. Computerized tomography and magnetic resonance imaging revealed a markedly abnormal appearance of cerebral white matter in the 4 affected patients tested, but clinical and other laboratory examinations failed to demonstrate evidence of central white matter dysfunction. Muscle biopsies and brain imaging were normal in all clinically unaffected family members. On the basis of the genetics, muscle biopsy findings and cerebral white matter changes, we conclude that this constellation represents a hitherto undescribed 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.
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.
