DeCure for Amyotrophic lateral sclerosis 27, juvenile
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis 27, juvenile — 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 moduleAmyotrophic lateral sclerosis 27, juvenile 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 amyotrophic lateral sclerosis 27, juvenile 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
serine palmitoyltransferase long chain base subunit 1 (SPTLC1) — SPTLC1 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 vsddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7K0K · 2.6 Å · ligand 3-Dehydrosphinganine (VSD). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 study of 57 patients with young-adult ALS (onset between 20 and 40 years) found that 59.6% had a predominant upper motor neuron phenotype, compared with 17.4% in a group of 450 adult-onset patients. In the young-adult group, those with the p-UMN phenotype had a median survival of 74 months (range 10–226, 95% CI 60.61–87.38), while those with the classic phenotype had a median survival of 56 months (range 6–106, 95% CI 48.65–63.34). The p-UMN group also showed a marked male excess of 5.8:1, versus 1.1:1 in the classic phenotype. A 2009 report described two juvenile familial cases from a rural Finnish family, noting a mild course in one and noticeable progression over 10 months in the other.
No drug has been shown to alter the course of juvenile or young-adult ALS specifically. A 2005 review stated that riluzole remains the only available therapy for ALS, with only marginal effects on survival. The same review noted that beta-lactam antibiotics, minocycline, growth factors, and heat-shock protein co-inducers were being investigated preclinically, but cautioned that the field had a long-standing failure to transfer therapeutic compounds to the clinic. A 2007 review of clinical trials listed no effective therapies beyond riluzole, and a 2017 review stated that no treatment existed for ALS, though edaravone had been approved in Japan and was pending in the US.
What is missing is any clinical trial data specific to juvenile or young-adult ALS. The 2008 natural history study did not test any intervention. The later reviews and trial catalogues cover adult ALS broadly; no trial has been designed or funded to test a drug in this younger subgroup. Patient stratification by phenotype and age at onset, which the 2008 data suggest matters for survival, has not been incorporated into any completed or ongoing drug trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 99 citations
Natural history of young-adult amyotrophic lateral sclerosis
AbstractBACKGROUND: Amyotrophic lateral sclerosis (ALS) affects people of all ages, but whether the wide range of age at onset is due to distinct diseases or merely reflects phenotypic variability of the same disorder is still unknown. The purpose of this study is to describe clinical and prognostic features of young-adult ALS, with onset before age 40 years, and to compare them with features of the common adult-onset type. METHODS: We analyzed clinical features and long-term follow-up of 57 young-adult ALS patients, with disease onset between 20 and 40 years, and compared them with 450 patients affected by adult-onset ALS. RESULTS: We found that the majority of young-adult patients showed a predominant upper motor neuron (p-UMN) ALS, characterized by marked spastic paraparesis, with lower motor neuron signs confined to the upper limbs. The proportion of patients with p-UMN ALS phenotype was 59.6% in the young-adult patients and 17.4% in the adult-onset form (p < 0.0001). Young-adult ALS with p-UMN phenotype had longer survival than did the classic phenotype: median survival was 74 months (range 10-226, 95% CI 60.61-87.38) in the former and 56 months (range 6-106, 95% CI 48.65-63.34) in the latter (p = 0.03). In the young-adult patients, a marked male excess was observed in the p-UMN ALS group (5.8:1), whereas the ratio of men to women was 1.1:1 in the classic phenotype (p = 0.01). CONCLUSIONS: Our findings show that young-adult amyotrophic lateral sclerosis with the predominant upper motor neuron phenotype represents a distinctive clinical variant characterized by a unique clinical pattern, longer survival, and male prevalence.
Current Opinion in Neurology · 2005 · 62 citations
Amyotrophic lateral sclerosis: recent advances and future therapies
AbstractPURPOSE OF REVIEW: Amyotrophic lateral sclerosis is a rare but fatal motoneuron disorder. Despite intensive research riluzole remains the only available therapy, with only marginal effects on survival. Here we review some of the recent advances in the search for a disease-modifying therapy for amyotrophic lateral sclerosis. RECENT FINDINGS: A number of established agents have recently been re-investigated for their potential as neuroprotective agents, including beta-lactam antibiotics and minocycline. Progress has also been made in exploiting growth factors for the treatment of amyotrophic lateral sclerosis, partly due to advances in developing effective delivery systems to the central nervous system. A number of new therapies have also been identified, including a novel class of compounds, heat-shock protein co-inducers, which upregulate cell stress responses thereby mediating neuroprotection. Non-drug-based therapies are also under development, with progress in gene-silencing and stem cell therapies. SUMMARY: In the past few years, significant advances have been made in both our understanding of amyotrophic lateral sclerosis pathogenesis and the development of new therapeutic approaches. However, caution must be exercised in view of the long-standing failure to successfully transfer therapeutic compounds to the clinic. A deeper awareness in the research community of the need for clinically relevant preclinical studies, coupled with a better understanding of the issues surrounding clinical trial design for amyotrophic lateral sclerosis, offers hope that the growing list of validated preclinical therapeutics can finally yield an effective disease-modifying treatment.
Expert Opinion on Investigational Drugs · 2007 · 33 citations
Current clinical trials in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis is caused by selective degeneration of motor neurons in the brain and spinal cord. There are still no other effective therapies 10 years after the approval of riluzole for the treatment of amyotrophic lateral sclerosis, but advances in drug development and screening are substantially increasing the number of potential therapeutic agents. This review provides an overview of clinical trial methodology in amyotrophic lateral sclerosis followed by a systematic evaluation of drugs that are presently in Phase I, II and III clinical trials. There is an emphasis on the scientific evidence supporting the selection of each drug being tested, as well as on trial design.
Expert Opinion on Investigational Drugs · 2017 · 33 citations
Drugs in clinical development for the treatment of amyotrophic lateral sclerosis
AbstractINTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron progressive disorder for which no treatment exists to date. However, there are other investigational drugs and therapies currently under clinical development may offer hope in the near future. Areas covered: We have reviewed all the ALS ongoing clinical trials (until November 2016) and collected in Clinicaltrials.gov or EudraCT. We have described them in a comprehensive way and have grouped them in the following sections: biomarkers, biological therapies, cell therapy, drug repurposing and new drugs. Expert opinion: Despite multiple obstacles that explain the absence of effective drugs for the treatment of ALS, joint efforts among patient's associations, public and private sectors have fueled innovative research in this field, resulting in several compounds that are in the late stages of clinical trials. Drug repositioning is also playing an important role, having achieved the approval of some orphan drug applications, in late phases of clinical development. Endaravone has been recently approved in Japan and is pending in USA.
Frontiers in Pharmacology · 2018 · 28 citations · open access
Amyotrophic Lateral Sclerosis (ALS) and Adenosine Receptors
AbstractIn the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS). Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early-symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing towards a beneficial role of A2A receptors (A2AR), most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signalling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression
AbstractThis paper presents two juvenile cases of familial amyotrophic lateral sclerosis. They are the first and fourth child in a family with seven children from the eastern part of Finland. All seven children, as well as the parents, were examined by our group. In the first case the disease showed a rather mild course, while in the second a noticeable progression was observed even during a period of 10 months. The patients come from a rural area with a stable population and low immigration, which may favor an enrichment of certain genes and therefore support the possible hereditary basis for the disease.
The Journal of Clinical Pharmacology · 2005 · 15 citations
Clinical Trials in Amyotrophic Lateral Sclerosis: The Tenuous Past and the Promising Future
AbstractThe past decade of research in amyotrophic lateral sclerosis has contributed to a greater understanding of the disease process, the development of relevant animal models, and the identification of several therapeutic approaches that may delay disease progression. Completed and ongoing clinical trials and the process of selecting drugs for clinical trials are presented.
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.
