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DeCure for Autosomal recessive Parkinson disease 14

DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive Parkinson disease 14 — 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 module1 genesLead labNeuro
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NeuroDOID:0060900$DeCureNeuro

The disease map

Disease moduleAutosomal recessive Parkinson disease 14 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 autosomal recessive parkinson disease 14 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

A 2024 cohort study examined 16 carriers of autosomal recessive Parkinson’s gene variants: 9 with biallelic or compound heterozygous PRKN mutations, 4 heterozygous PRKN carriers, and 3 with biallelic PINK1 mutations. The average levodopa equivalent daily dose was 806.8 mg in PRKN carriers and 765 mg in PINK1 carriers, with a wide range from 152 to 1810 mg. Most patients responded to low or moderate levodopa doses. Dopamine agonists were often effective both as initial and long-term therapy. Amantadine was used successfully in 8 of 13 PRKN carriers and 1 of 3 PINK1 carriers, including patients who could not tolerate levodopa or dopamine agonists. Some patients did well without any levodopa decades after disease onset.

Earlier genetic studies identified several genes for autosomal recessive Parkinson’s disease: PARKIN, DJ-1, and PINK1. A 2004 report described the cloning of LRRK2, a gene on chromosome 12p11.2-q13.1 that encodes a 2527-amino acid protein with a kinase domain. Mutations in LRRK2 cause an autosomal-dominant, late-onset familial parkinsonism. That discovery is not directly relevant to autosomal recessive forms, but it illustrates the genetic heterogeneity of Parkinson’s disease.

The 2024 cohort is small, with only 16 patients, and no control group. The study does not report survival, response rates as proportions, or long-term outcomes such as motor complications or quality of life. The evidence for amantadine and dopamine agonists in recessive Parkinson’s rests on this single observational series. What is still missing is a larger, prospectively defined trial that stratifies patients by specific gene (PRKN, PINK1, DJ-1) and compares treatment regimens head-to-head, with standardised endpoints and adequate follow-up. Funding for such trials remains scarce.

Evidence

Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.

Preprints.org · 2024 · 0 citations · open access

Precision Dopaminergic Treatment in a Cohort of Parkinson’s disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review

AbstractIntroduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

https://doi.org/10.20944/preprints202405.0524.v1
Parkinson s Disease · 2007 · 0 citations

Genetics: DJ-1 in Parkinson’s Disease

AbstractOur genetic knowledge of Parkinson’s disease (PD) is moving forward at an impressive speed. In less than 10 years, family-based linkage analysis and positional cloning have led to the identification of several genes for autosomal recessive PD [PARKIN (1), DJ-1 (2), and PINK-1 (3)], autosomal dominant PD, [α-synuclein (4), UCHL1 (5), NR4A2 (6), and LRRK2 (7,8)] and a number of potential genetic risk factors for idiopathic PD (9).

https://doi.org/10.3109/9781420019223-10
Science s STKE · 2004 · 0 citations

A Novel Kinase Implicated in Parkinson's Disease

AbstractTwo groups have implicated a gene encoding a putative kinase of unknown function in familial Parkinson's disease. Parkinson's disease, the second most common neurodegenerative disease, results from the degeneration of a set of dopaminergic neurons. The recent identification of several genes implicated in familial forms of parkinsonism has begun to provide clues to the underlying molecular mechanisms. Two groups identified a novel gene at the PARK8 locus on chromosome 12p11.2-q13.1 that had previously been linked to an autosomal-dominant, late-onset, familial form of parkinsonism (see Preview by Shen). Paisán-Ruíz et al. identified a missense mutation within a kinase-domain-containing transcript that segregated with the disease in four families, as well as a different mutation in the same gene in a fifth family. Zimprich et al. identified six segregating mutations in the same gene; two of these affected the same amino acid residues found in the Paisán-Ruíz study. The affected gene, which has been named LRRK2 ( leucine-rich repeat kinase 2 , with the protein called LRRK2 by Zimprich et al. and dardarin by Paisán-Ruíz et al. ), encodes a 2527-amino acid protein. It is predicted to contain a leucine-rich domain, a Ras superfamily domain (Roc, for Ras in complex proteins), a COR (C-terminal of Roc) domain, a nonreceptor tyrosine kinase domain, and a WD40 domain. Although the role of LRRK2-dardarin remains unknown, it likely functions as a kinase, and identification of its functions and substrates may help unravel the molecular underpinning of Parkinson's disease. C. Paisán-Ruíz, S. Jain, E. W. Evans, W. P. Gilks, J. Simón, M. van der Brug, A. López de Munain, S. Aparicio, A. Martinez Gil, N. Khan, J. Johnson, J. Martinez, D. Nicholl, I. M. Carrera, A. Saénz Peña, R. de Silva, A. Lees, J. F. Martí-Massó, J. Pérez-Tur, N. W. Wood, A. B. Singleton, Cloning of the gene containing mutations that cause PARK8 -linked Parkinson's disease. Neuron 44 , 595-600 (2004). [Online Journal] A. Zimprich, S. Biskop, P. Leitner, P. Lichtner, M. Farrer, S. Lincoln, J. Kachergus, M. Hulihan, R. J. Uitti, D. B. Calne, A. J. Stoessl, R. F. Pfeiffer, N. Patenge, I. Carballo Carbajal, P. Vieregge, F. Asmus, B. Müller-Myhsok, D. W. Dickson, T. Meitinger, T. M. Strom, Z. K. Wszolek, T. Gasser, Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44 , 601-607 (2004). [Online Journal] J. Shen, Protein kinases linked to the pathogenesis of Parkinson's disease. Neuron 44 , 575-577 (2004). [Online Journal]

https://doi.org/10.1126/stke.2602004tw424

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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