DeCure for Cerebellar ataxia-hypogonadism syndrome
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for cerebellar ataxia-hypogonadism syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebellar ataxia-hypogonadism syndrome maps to a 2-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 cerebellar ataxia-hypogonadism syndrome 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
ring finger protein 216 (RNF216) — RNF216 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 2-methoxyethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7M4O · 2.21 Å · ligand 2-(2-METHOXYETHOXY)ETHANOL (PG0). Experimental structure, not a prediction.
What the evidence adds up to
A 2001 case report describes permanent and severe cerebellar ataxia in a young woman after high-dose cytosine arabinoside, with corticospinal tract damage also occurring. The authors state that early recognition to stop drug administration remains the only method to reduce risk. No other evidence of drug-induced ataxia is presented in these abstracts.
A 2024 review of hereditary ataxias notes that the rarity of certain forms limits insights into disease etiology and identification of target pathways, and that a lack of suitable models hampers efforts to understand molecular pathophysiology and test novel therapies. A 2020 review of treatable cerebellar ataxias discusses metabolic, immune-mediated, inflammatory and hereditary causes that can be diagnosed and treated with targeted therapies, but does not name any specific drug that reverses ataxia in the syndrome described here.
A 2017 rat study examined riluzole in a 3-acetylpyridine model of ataxia. In that experiment, Purkinje cell sodium firing frequency was 22.53±5.49 Hz in controls, 6.46±0.23 Hz in ataxic rats, and 31.34±4.07 Hz in riluzole-treated rats; calcium frequency was 4.22±2.02 Hz in controls, 1.52±1.19 Hz in ataxic rats, and 3.88±1.37 Hz in riluzole-treated rats. The authors conclude these spectral changes may be a basis for developing possible new treatment strategies, but no human data on riluzole for this condition are provided.
A 2024 clinical case describes a 16-year-old with progressive ataxia, cerebellar atrophy, demyelinating neuropathy, and hypergonadotropic hypogonadism, but offers no treatment outcome. A 2022 analytical review covers diagnostic methods and rehabilitation principles for cerebellar ataxia but does not report any drug that halts or reverses the disease. What is still missing: a dedicated clinical trial for cerebellar ataxia-hypogonadism syndrome, funding for patient stratification by genetic subtype, and any human efficacy data for riluzole or other agents in this specific disorder.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 1975 · 90 citations
Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism*
AbstractAn ataxia-hypogonadism syndrome is reported in at least four of 15 family members (two brothers and two sisters). Consanguinity could be proven by genealogical studies; parents were second cousins. The onset of cerebellar ataxia in three sibs was at about 12-20 years, in the proposita at 33-38 years; progression was very slow. Hypogonadotropic hypogonadism was reflected in failure of maturation of secondary sexual characteristics, eunuchoidism, absence of libido and infertility. The concurrence of hereditary ataxia and hypogonadotropic hypogonadism is discussed and explained as pleiotropic effects caused by the homozygous state of a rare autosomal recessive gene. A review of the literature suggests that this is a previously undescribed disorder.
Permanent cerebellar toxicity of cytosine arabinoside (Ara C) in a young woman
AbstractThis report provides the first videotape example of a patient with permanent cerebellar ataxia from high dose cytosine arabinoside. This case was unusual in that the patient was young, the effects are seemingly permanent and severe, and corticospinal tract damage also occurred. Early recognition to stop drug administration remains the only method to reduce risk.
Hereditary Ataxias: From Bench to Clinic, Where Do We Stand?
AbstractCerebellar ataxias are a wide heterogeneous group of movement disorders. Within this broad umbrella of diseases, there are both genetics and sporadic forms. The clinical presentation of these conditions can exhibit a diverse range of symptoms across different age groups, spanning from pure cerebellar manifestations to sensory ataxia and multisystemic diseases. Over the last few decades, advancements in our understanding of genetics and molecular pathophysiology related to both dominant and recessive ataxias have propelled the field forward, paving the way for innovative therapeutic strategies aimed at preventing and arresting the progression of these diseases. Nevertheless, the rarity of certain forms of ataxia continues to pose challenges, leading to limited insights into the etiology of the disease and the identification of target pathways. Additionally, the lack of suitable models hampers efforts to comprehensively understand the molecular foundations of disease's pathophysiology and test novel therapeutic interventions. In the following review, we describe the epidemiology, symptomatology, and pathological progression of hereditary ataxia, including both the prevalent and less common forms of these diseases. Furthermore, we illustrate the diverse molecular pathways and therapeutic approaches currently undergoing investigation in both pre-clinical studies and clinical trials. Finally, we address the existing and anticipated challenges within this field, encompassing both basic research and clinical endeavors.
Clinical Parkinsonism & Related Disorders · 2020 · 16 citations · open access
Treatable cerebellar ataxias
AbstractCerebellar ataxic syndrome is a heterogenous class of disorders which can result from a miscellany of causes- genetic or acquired. There are a few metabolic, immune mediated, inflammatory and hereditary causes of ataxia which can be diagnosed from the gamut of possibilities, offering great relief to the ailing patient, their family and the treating physician. A pragmatic algorithm for diagnosing treatable causes of ataxia includes a thorough clinical history, meticulous examination for associated signs and an investigative mind to clinch the diagnosis. With novel diagnostic techniques and targeted therapies, early diagnosis and treatment can lead to favourable outcomes. In this review, diseases presenting predominantly as cerebellar ataxia and are treatable by targeted therapies are discussed.
Psychiatry and Clinical Neurosciences · 2002 · 15 citations · open access
Beneficial effects of tandospirone on ataxia of a patient with Machado‐Joseph disease
AbstractTandospirone citrate (tandospirone) is an anti-anxiety drug that acts by combining with serotonin receptor (5-hydroxytryptamine-1 A [5-HT1A]). Recently, there have been a few reports of its potential role in the treatment of cerebellar ataxia. We report the first case of a patient with Machado-Joseph disease in which we successfully treated cerebellar ataxia. In addition, his leg pain, insomnia, anorexia, and depression, which are thought to be related to 5-HT1A receptors, were also remarkably alleviated by treatment with tandospirone.
Basic and Clinical Neuroscience Journal · 2017 · 3 citations · open access
Power Spectral Density Analysis of Purkinje Cell Tonic and Burst Firing Patterns From a Rat Model of Ataxia and Riluzole Treated
AbstractINTRODUCTION: Purkinje Cell (PC) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3-acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP treated were investigated to determine changes in the firing properties. Difference in the power spectra of tonic and burst firing was assessed. Furthermore, the role of calcium-activated potassium channels in the power spectra was evaluated. METHODS: Analysis was performed using Matlab. Power spectral density (PSD) of PCs output were obtained. Peak frequencies were extracted from the spectrum and statistical comparisons were done. In addition, a multi-compartment computational model of a Purkinje cell was used. This computational stimulation allowed us to study the changes in the power spectral density of the PC output as a result of alteration in ion channels. RESULTS: Spectral analysis showed that in the spectrum of tonic and burst firing pattern only high sodium frequency and low calcium frequency was seen, respectively. In addition, there was a significant difference between the frequency components of PCs firing obtained from normal, ataxia and riluzole treated rats. Results indicated that sodium firing frequency of normal, ataxic and treated PCs occurred in approximate frequency of 22.53±5.49, 6.46±0.23, and 31.34±4.07 Hz, respectively; and calcium frequency occurred in frequency of 4.22±2.02, 1.52±1.19, and 3.88±1.37 Hz, respectively. The simulation results demonstrated that blockade of calcium-activated potassium channels in the PC model changed the PSD of the PC model firing activity. This change was similar to PSD changes in ataxia condition. CONCLUSION: These alterations in the spectrum of PC output may be a basis for developing possible new treatment strategies to improve cerebellar ataxia.
Clinical Reasoning: Clinical Manifestations and Diagnostic Challenges in a 16-Year-Old With Early-Onset Ataxia
AbstractA 16-year-old adolescent girl presented with progressive walking imbalance, uncoordination of her limbs, impaired proprioceptive sensation distal to her wrists and ankles, and sensorineural hearing loss. Her evaluation revealed diffuse cerebellar atrophy, a demyelinating neuropathy, and hypergonadotropic hypogonadism. In this article, we present a systematic approach to a patient with early-onset ataxia, cerebellar atrophy, and demyelinating neuropathy.
Bulletin of the Medical Institute REAVIZ (REHABILITATION DOCTOR AND HEALTH) · 2022 · 1 citations · open access
To the question of differentiation of ataxias (analytical review)
AbstractBased on the analysis of numerous studies, the authors summarized the current understanding of the problem of cerebellar ataxia. Issues related to the cause of the development of coordinating disorders, pathophysiological mechanisms of their occurrence, depending on trigger factors, are consistently covered. The features of the clinical course of acquired and congenital ataxias are systematized, their differential diagnostic differences are presented. Methods for diagnosing cerebellar ataxia are highlighted, diagnostic information content of laboratory, genetic, instrumental research methods is shown. The main directions of drug and non-drug methods of treatment of cerebellar ataxia are considered, their effectiveness is given. The main principles of rehabilitation of this group of patients are formulated.
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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