DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for coenzyme Q10 deficiency, primary, 3 — 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 moduleCoenzyme Q10 deficiency, primary, 3 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 coenzyme q10 deficiency, primary, 3 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
Primary coenzyme Q10 deficiency results from mutations in at least 10 genes involved in CoQ10 biosynthesis. The condition is clinically and genetically heterogeneous, with five major phenotypes described: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. Cerebellar ataxia and nephrotic syndrome are the most common presentations. Onset ranges from the neonatal period to 18 years. In a 2024 review of 24 neonatal-onset cases with COQ4 mutation, hyperlactataemia occurred in 75% (18/24). Survival time for these 24 cases was 60.0 ± 98.0 days (95% CI 0–252.0 days). Mortality was 75% (9/12) in Chinese cases and 91.7% (11/12) in other regions, a difference that was not statistically significant (P = 0.27). Only 9 of the 24 patients received exogenous CoQ10 treatment, and all 4 surviving patients had received CoQ10 supplementation. The authors state that the prognosis of COQ4 mutation in the neonatal period indicates a low survival rate and a poor prognosis, possibly because CoQ10 supplementation does not respond well to treatment.
In older patients, responses to oral CoQ10 have been reported. A 2006 study of three sporadic patients with isolated myopathy and muscle CoQ10 levels below 50% of normal found that high-dose oral CoQ10 supplementation improved muscle strength dramatically and normalised serum creatine kinase. A 2008 report of two patients with a homozygous COQ2 missense mutation noted that oral CoQ10 may stop the progression of encephalopathy, but no benefit was observed with respect to the evolution of renal disease. A 2019 case report of a 3-month-old boy with a COQ4 mutation found that convulsive symptoms improved significantly after CoQ10 treatment. A 2023 review states that patients may respond well to oral CoQ10 supplementation, provided the condition is recognised early, before irreversible tissue damage has occurred. The same review notes disparities between previous review articles regarding the usefulness of CoQ10 supplementation and highlights unresolved issues that require further research.
The 2014 review states that identification of CoQ10 deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation. However, the 2024 neonatal COQ4 series explicitly contradicts this for that genotype, reporting that CoQ10 supplementation does not respond well to treatment and that the mechanism by which COQ4 gene defects lead to deficiency remains incompletely understood. The 2023 update also notes potential problems relating to CoQ10 supplementation in primary CoQ10 deficiency. Across all abstracts, no controlled trial data are presented; evidence comes from case reports and small case series.
What is still missing: adequately powered prospective clinical trials, standardised dosing regimens, validated biomarkers for early diagnosis before irreversible damage, and a clear understanding of why some genotypes (notably COQ4 in neonates) respond poorly to supplementation while others show dramatic improvement. Patient stratification by genotype, age at onset, and specific organ involvement is needed before any reliable treatment protocol can be established. Funding for multicentre natural history studies and for mechanistic work on CoQ10 transport and tissue distribution remains inadequate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2008 · 253 citations · open access
Early Coenzyme Q10 Supplementation in Primary Coenzyme Q10 Deficiency
AbstractPrimary coenzyme Q10 deficiency is considered to be the only treatable mitochondrial disorder, since patients have a response \nto oral coenzyme Q10 supplementation. The disease \nusually manifests with nephropathy and encephalomyopathy. \n1 It has been shown that oral coenzyme Q10 may stop the progression of encephalopathy, but no benefit from this therapy \nhas been noted with respect to the evolution of renal disease associated with this deficiency.1,2 We now describe the results of long-term coenzyme Q10 supplementation in two patients \nwith coenzyme Q10 deficiency caused by a homozygous \nmissense mutation in the COQ2 gene.3,4
AbstractThree unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complexes I and III, and CoQ10 levels below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle strength dramatically and normalized serum CK.
AbstractCoenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant and plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Due to the multiplicity of roles in cell function, it is not surprising that a deficiency in CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation; we have attempted to resolve the disparities between previous review articles regarding the usefulness or otherwise of CoQ10 supplementation in these disorders. In addition, we have highlighted several of the potential problems relating to CoQ10 supplementation in primary CoQ10 deficiency, as well as identifying unresolved issues relating to these disorders that require further research.
Molecular Syndromology · 2014 · 44 citations · open access
Clinical Presentations of Coenzyme Q10 Deficiency Syndrome
AbstractCoenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation.
International Journal of Research in Medical Sciences · 2015 · 7 citations · open access
Coenzyme Q10 therapy in current clinical practice
AbstractCoenzyme Q10 (CoQ10) is a naturally occurring, lipid soluble, essential compound and is also known as ubiquinone. CoQ10 acts as an intermediate of the electron transport chain situated in membrane of mitochondria and vital for ATP production and cellular respiration. CoQ10 also serves as an intercellular antioxidant. All the clinical use of CoQ10 are based upon these two functions. CoQ10 levels are altered in a number of oncological as well as non-oncological diseases. Furthermore, recent data indicate that CoQ10 has an impact on the expression of many genes involved in metabolism, cellular transport, transcription control, and cell signaling, making CoQ10 a potent gene regulator. CoQ10 supplementation is useful in diseases associated with CoQ10 deficiency which includes primary and secondary CoQ10 deficiencies, fibromyalgia, diabetes mellitus, mitochondrial diseases, neurodegenerative diseases, cardiovascular disease, cancer, male infertility and periodontal disease. Clinical presentations of severe CoQ10 deficiency include severe infantile multisystemic disease, encephalomyopathy, isolated myopathy cerebellar ataxia and Leigh syndrome with growth retardation. Oral CoQ10 administration can correct CoQ10 deficiency since it increases CoQ10 tissue levels. CoQ10 therapy has no serious side effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Future trends involving CoQ10 in many diseases needs more clinical trials for better understanding of CoQ10 efficacy.
Clinical characteristics and genetic analysis of primary coenzyme Q10 deficiency caused by COQ4 gene mutation
AbstractObjective
To explore the clinical and genetic characteristics of primary coenzyme Q10 deficiency caused by coenzyme Q4 (COQ4) variants.
Methods
Clinical data were collected, while COQ4 gene was sequenced.
Results
Here were reported a boy of 3 months old who came to our hospital presented with feeding difficulties, repeated respiratory infections, convulsions for 3 months. He was subsequently diagnosed as cerebral atrophy, and growth retardation. All exons were sequenced.c.211G>A(p.A71T, maternal), c. 436T>A(p.F146I, paternal) were detected. After treatment with coenzyme Q10, the convulsive symptoms improved significantly. Literature review revealed that totally 14 cases with primary coenzyme Q10 deficiency caused by COQ4 gene mutation were reported. The onset age varies from neonatal to 18 years old, and the clinical manifestations are heterogeneous, including cardiomyopathy, epilepsy, ataxia, cerebellar atrophy, respiratory insufficiency, and growth retardation.
Conclusion
For cases with atypical clinical manifestations of primary coenzyme Q10 deficiency, gene detection is helpful for an early diagnosis and treatment.
Key words:
Primary coenzyme Q10 deficiency; COQ4 gene; Gene mutation
Frontiers in Pediatrics · 2024 · 3 citations · open access
The Spectrum of clinical manifestations in newborns with the COQ4 mutation: case series and literature review
AbstractBackground Coenzyme Q10 (CoQ10) plays an important role in the electron transport chain within the human mitochondrial respiratory chain. The manifestations of this deficiency exhibit a diverse range. This study investigates the clinical manifestations of primary coenzyme Q10 deficiency in neonates with the COQ4 mutation to improve the diagnosis of the disease and the prognosis through targeted treatment. Methods We report 4 patients with primary coenzyme Q10 deficiency by COQ4 variants in neonates. A comprehensive literature search and review for original articles and case reports with COQ4 mutation published from January 1989 to November 2023 was performed through Pubmed. We review clinical manifestations, diagnostic approaches, and treatment monitoring in these and 20 previously reported patients. Results Within the cohort of four cases examined, three females and one male were identified from two distinct families. Specifically, case 1 and 2 consisted of monoamniotic twins. Cases 3 and 4 were siblings. A comprehensive review of 20 cases involving neonatal-onset COQ4 mutation was conducted. Half of the cases are Chinese. There was no statistically significant difference in the mortality between Chinese (9/12, 75%) and other regions (11/12, 91.7%) ( P = 0.27). The survival time for the 24 cases was 60.0 ± 98.0 days (95% confidence interval CI: 0–252.0 days). The incidence of prenatal abnormalities in preterm infants was significantly higher than that in full-term infants (66.7% vs. 16.7%, P = 0.02). Hyperlactatemia was one of the most common manifestations, accounting for 75% of cases (18/24). Twenty of the 24 cases were diagnosed by whole exome sequencing. Only 9 patients received exogenous coenzyme Q10 treatment, and all the 4 surviving patients received coenzyme Q10 supplementation. Conclusion The prognosis of COQ4 mutation in the neonatal period indicates a low survival rate and an poor prognosis. This may be due to the incomplete understanding of the mechanism of how COQ4 gene defects lead to coenzyme Q10 deficiency and why CoQ10 supplementation does not respond well to treatment. To improve the diagnostic rate, in addition to genetic testing, mitochondrial functional verification should be prioritized in southern China, where the incidence is relatively high. It will facilitate more in-depth mechanistic studies.
Sage Journals Data · 2023 · 0 citations · open access
sj-docx-1-icr-10.1177_11795476231188061 – Supplemental material for Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature
AbstractSupplemental material, sj-docx-1-icr-10.1177_11795476231188061 for Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature by Mahsa Hojabri, Abolfazl Gilani, Rana Irilouzadian, Habibe Nejad biglari and Roham Sarmadian in Clinical Medicine Insights: Case Reports
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.
