DeCure for Neurodegeneration with brain iron accumulation
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for neurodegeneration with brain iron accumulation — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeurodegeneration with brain iron accumulation maps to a 10-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 neurodegeneration with brain iron accumulation 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
carnitine O-acetyltransferase (CRAT) — CRAT 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 152drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1S5O · 1.8 Å · ligand CARNITINE (152). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 case report described one patient with aceruloplasminemia, a disorder of iron metabolism that causes neurodegeneration with brain iron accumulation (NBIA). After ten months of treatment with the iron chelator desferrioxamine, brain iron stores decreased, plasma lipid peroxidation was reduced, and progression of neurological symptoms was prevented. The authors suggested early chelation might be useful for such patients. No other patients or controls were reported.
A 2014 review proposed that iron accumulation in the brain might be a mechanism in postoperative cognitive dysfunction, and speculated that iron chelators could offer neuroprotection. This review did not study NBIA and did not report any patient data.
A 2013 report on the Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON) project stated that as of that date there was no proven therapy to halt or reverse pantothenate kinase-associated neurodegeneration (PKAN), the most common NBIA form, or any other NBIA. The report attributed the absence of adequately powered randomised clinical trials not to a lack of therapeutic options but to the rarity of the disease, the lack of patient registries, and the fragmentation of therapeutic research worldwide.
A 2021 review of precision therapies for NBIA disorders concluded that therapeutic options remain very limited, with no proven disease-modifying treatments at present. It noted that several approaches, including gene therapy, gene editing, and substrate replacement therapies, are under development. A 2019 review of NBIA models reported that only two of the fifteen known causative genes code for iron-proteins, and that how iron participates in the pathogenesis of most NBIA remains unclear, essentially for the lack of experimental models that fully recapitulate the human phenotype. What is still missing are adequately powered randomised clinical trials, patient registries, and experimental models that replicate the human disease, along with the funding and coordinated international effort needed to produce them.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 1997 · 175 citations
Use of desferrioxamine in the treatment of aceruloplasminemia
AbstractAceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism resulting in neurodegeneration of the retina and basal ganglia. We report here on the treatment of a patient who developed progressive extrapyramidal symptoms that included blepharospasm, grimacing, and rigidity associated with increased iron deposition in the brain and visceral organs. Treatment for 10 months with the iron chelator desferrioxamine decreased brain iron stores, prevented progression of the neurological symptoms, and reduced plasma lipid peroxidation. These data suggest that early treatment with this chelator may be useful in such patients to diminish central nervous system iron accumulation and to prevent or ameliorate neurological symptoms associated with neurodegeneration.
Pharmaceuticals · 2019 · 91 citations · open access
Neurodegeneration with Brain Iron Accumulation Disorders: Valuable Models Aimed at Understanding the Pathogenesis of Iron Deposition
AbstractNeurodegeneration with brain iron accumulation (NBIA) is a set of neurodegenerative disorders, which includes very rare monogenetic diseases. They are heterogeneous in regard to the onset and the clinical symptoms, while the have in common a specific brain iron deposition in the region of the basal ganglia that can be visualized by radiological and histopathological examinations. Nowadays, 15 genes have been identified as causative for NBIA, of which only two code for iron-proteins, while all the other causative genes codify for proteins not involved in iron management. Thus, how iron participates to the pathogenetic mechanism of most NBIA remains unclear, essentially for the lack of experimental models that fully recapitulate the human phenotype. In this review we reported the recent data on new models of these disorders aimed at highlight the still scarce knowledge of the pathogenesis of iron deposition.
Tremor and Other Hyperkinetic Movements · 2021 · 20 citations · open access
Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation
AbstractBackground: Neurodegeneration with brain iron accumulation (NBIA) disorders comprise a group of rare but devastating inherited neurological diseases with unifying features of progressive cognitive and motor decline, and increased iron deposition in the basal ganglia. Although at present there are no proven disease-modifying treatments, the severe nature of these monogenic disorders lends to consideration of personalized medicine strategies, including targeted gene therapy. In this review we summarize the progress and future direction towards precision therapies for NBIA disorders. Methods: This review considered all relevant publications up to April 2021 using a systematic search strategy of PubMed and clinical trials databases. Results: We review what is currently known about the underlying pathophysiology of NBIA disorders, common NBIA disease pathways, and how this knowledge has influenced current management strategies and clinical trial design. The safety profile, efficacy and clinical outcome of clinical studies are reviewed. Furthermore, the potential for future therapeutic approaches is also discussed. Discussion: Therapeutic options in NBIAs remain very limited, with no proven disease-modifying treatments at present. However, a number of different approaches are currently under development with increasing focus on targeted precision therapies. Recent advances in the field give hope that novel strategies, such as gene therapy, gene editing and substrate replacement therapies are both scientifically and financially feasible for these conditions. Highlights: This article provides an up-to-date review of the current literature about Neurodegeneration with Brain Iron Accumulation (NBIA), with a focus on disease pathophysiology, current and previously trialed therapies, and future treatments in development, including consideration of potential genetic therapy approaches.
Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON) - an integrated strategy under FP7 to improve research, treatment, and care in neurodegeneration with brain iron accumulation
AbstractAims: Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous group of rare hereditary neurodegenerative disorders characterized by high levels of brain iron. Many NBIA cases are characterized by early childhood onset and rapid progression to disability and death. The most frequent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN). Currently, there is no proven therapy to halt or reverse PKAN or any other form of NBIA. This is especially unfortunate as both the iron accumulation in NBIA and the biochemical defect in PKAN are predicted to be amenable to drug-based treatment. Thus, the absence of adequately powered randomized clinical trials is not due to a lack of therapeutic options but to the rarity of the disease, the lack of patient registries, and the fragmentation of therapeutic research worldwide.
The role of iron accumulation in postoperative cognitive dysfunction
AbstractBackground Postoperative cognitive dysfunction (POCD) is a common neurological complication after anesthesia and surgery,especially prevalent in the elderly.Iron accumulation in the brain is an initial cause of neurodegeneration,it gives rise to neuronal degeneration and necrosis by arousing oxidative stress.Objective This review aims to investigate the role of iron accumulation in POCD.Content The distribution of brain iron,iron metabolism protein function,the relationship of excessive iron levels in the brain and neurodegeneration,as well as the progress of iron accumulation in POCD are described in the article.Trend Iron accumulation may be an important mechanism of POCD,the neuroprotection of iron chelator is expected to provide new target for the management of POCD.
Key words:
Iron accumulation; Neurodegeneration; Postoperative cognitive dysfunction
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.
