DeCure for X-linked sideroblastic anemia with ataxia
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for X-linked sideroblastic anemia with ataxia — 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 moduleX-linked sideroblastic anemia with ataxia 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 x-linked sideroblastic anemia with ataxia 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
ATP binding cassette subfamily B member 7 (ABCB7) — ABCB7 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 23PI · 2.33 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
X-linked sideroblastic anaemia with ataxia is a rare disorder caused by mutations in the ABCB7 gene at Xq12-q13, which encodes a mitochondrial transporter involved in iron homeostasis. As of 1990, only three families had been reported, each with a distinct missense mutation. A fourth family with a novel ABCB7 mutation was later described. The anaemia is usually mild and asymptomatic, meaning the ataxia may be the presenting feature and the underlying diagnosis overlooked.
A 1992 study identified a highly polymorphic dinucleotide repeat within intron 7 of the ALAS2 gene, which is the defective locus in X-linked pyridoxine-responsive sideroblastic anaemia. Using this marker, the gene for that form of sideroblastic anaemia was placed on the multipoint linkage map of the X chromosome. The same study noted that close linkage between DXS14 and sideroblastic anaemia with ataxia had previously been excluded, demonstrating that there are at least two distinct loci for X-linked sideroblastic anaemia — one involving ALAS2 and another involving ABCB7.
A 2009 review of cerebellar ataxias noted that the clinical diagnosis of ataxia subtypes is complicated by substantial overlap of phenotypes between genetic forms. The review described the identification of causative mutations in many hereditary ataxias and the development of relevant animal models, but did not report any specific therapeutic results for X-linked sideroblastic anaemia with ataxia. No drug treatment for this condition was mentioned in any of the abstracts.
What is still missing is any clinical trial data — no drug has been tested in patients with this specific disorder. The small number of identified families (four as of the most recent report) makes patient stratification and recruitment for a trial difficult. Funding for natural history studies and for preclinical work on ABCB7-related iron handling would be needed before any candidate therapy could be evaluated.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2009 · 187 citations
Cerebellar ataxias
AbstractPURPOSE OF REVIEW: The term 'cerebellar ataxias' encompasses the various cerebellar disorders encountered during daily practice. Patients exhibit a cerebellar syndrome and can also present with pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. The clinical diagnosis of subtypes of ataxias is complicated by the salient overlap of the phenotypes between genetic subtypes. The identification of the causative mutations of many hereditary ataxias and the development of relevant animal models bring hope for effective therapies in neurodegenerative ataxias. RECENT FINDINGS: We describe the current classification of cerebellar ataxias and underline the recent discoveries in molecular pathogenesis. Cerebellar disorders can be divided into sporadic forms and inherited diseases. Inherited ataxias include autosomal recessive cerebellar ataxias, autosomal dominant cerebellar ataxias/spinocerebellar ataxia) and episodic ataxias, and X-linked ataxias. From a motor control point of view, the leading theories of ataxia are based on neural representations or 'internal models' to emulate fundamental natural processes such as body motion. SUMMARY: Recent molecular advances have direct implications for research and daily practice. We provide a framework for the diagnosis of ataxias. For the first time, the therapeutic agents under investigation are targeted to deleterious pathways.
Journal of Neurology Neurosurgery & Psychiatry · 2001 · 47 citations · open access
X-linked sideroblastic anaemia with ataxia: another mitochondrial disease?
AbstractOBJECTIVES: The syndrome of X-linked sideroblastic anaemia with ataxia is rare, described only twice in the literature. The aim was to obtain clinical neurological and haematological data about this rare syndrome throughout adult life. METHODS: A family is described with two affected brothers and two affected maternal uncles. The family was evaluated clinically. Haematological investigations included full blood count, blood film, iron studies, free erythrocyte protoporphyrin (FEP) concentrations and a bone marrow examination where possible. RESULTS: Core neurological features included motor delay, ataxia evident from early childhood, and dysarthria. Neurological features were non-progressive until the fifth decade when slow progression became evident. Some family members showed mild spasticity. Patients usually have a mild asymptomatic anaemia or a borderline decreased mean corpuscular volume. Blood film examination showed Pappenheimer bodies. Bone marrow examination showed ring sideroblasts, indicating raised erythrocyte iron. Free erythrocyte protoporphyrin (FEP) concentrations were raised. CONCLUSIONS: Haematological features are subtle and can be easily overlooked, and individual patients may not display all the abnormal features. X-linked ataxias are rare and incorrect genetic advice may be given if the diagnostic haematological features of X-linked sideroblastic anaemia are overlooked. Males with early onset ataxia should have a haematological evaluation including a blood film, with a bone marrow examination if abnormal blood count indices and measurement of FEP concentrations raise suspicion. The condition has parallels with Pearson's syndrome and Friedreich's ataxia. All three conditions are associated with mitochondrial iron handling defects and ataxia. The human ATP binding cassette gene (hABC7) is a candidate gene and requires further investigation.
Identification of a highly polymorphic marker within intron 7 of the <i>ALAS2</i> gene and suggestion of at least two loci for X-linked sideroblastic anemia
AbstractWe have identified a compound dinucleotide repeat within intron 7 of the human erythroid 5-aminolevulinate synthase (ALAS2) gene with a minimum of 9 alleles and heterozygosity of 78%. ALAS2 was placed on the multipoint linkage map of the X chromosome in the pericentromeric region with the locus order: pter-(DXS255, TFE3, DXS146)-(DXS14, ALAS2, DXZ1)-AR-(DXS153, DXS159)-qter. No recombination was observed between ALAS2 and the centromere marker DXZ1. As ALAS2 has recently been shown to be the defective locus in X-linked pyridoxine-responsive sideroblastic anemia (PRSA), the ALAS2 marker has allowed placement of the gene for PRSA into the multipoint linkage map of the X chromosome. With the previous exclusion of close linkage between DXS14 and sideroblastic anemia with ataxia, our data show that there are at least two loci for X-linked sideroblastic anemia.
Revista española de seguros: Publicación doctrinal de Derecho y Economía de los Seguros privados · 1990 · 0 citations
La libre prestación de servicios en los Seguros de Vida: propuesta de Segunda Directiva "Seguros de Vida"
AbstractX-linked sideroblastic anemia and ataxia (XLSA-A) is a rare cause of early onset ataxia, which may be overlooked due to the usually mild asymptomatic anemia. The genetic defect has been identified as a mutation in the ABCB7 gene at Xq12-q13. The gene encodes a mitochondrial ATP-binding cassette (ABC) transporter protein involved in iron homeostasis. Until now only three families have been reported, each with a distinct missense mutation in this gene. We describe a fourth family with XLSA-A and a novel mutation in the ABCB7 gene.
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.
