DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Griscelli syndrome type 1 — 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 moduleGriscelli syndrome type 1 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 griscelli syndrome type 1 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
myosin VA (MYO5A) — MYO5A 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4J5L · 2.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Griscelli syndrome type 1 is a rare autosomal recessive disease caused by mutations in the MYO5A gene. The 2020 genetic analysis of three Egyptian patients identified two previously unreported nonsense mutations: c.2110C>T (p.Gln704*) in two siblings and c.463C>T (p.Arg155*) in an unrelated individual. All patients were born to consanguineous parents and presented in infancy with silvery-grey hair, skin hypopigmentation, and primary neurological deficits including hypotonia, developmental delay, intellectual disabilities, and seizures. The 2007 report describes a 20-year-old female with diffuse pigment dilution and circumscribed pigment loss over thighs and abdomen, who also experienced an accelerated phase with neurological deterioration; her survival beyond the first decade without specific therapy was noted as distinctive.
The 2021 case of a seven-year-old girl initially presented with fever and pancytopenia, was treated for infectious disease after malignancies were ruled out, and was discharged after two weeks. Ten days later she developed new symptoms, and microscopic hair shaft analysis revealed abnormal pigment distribution, leading to the diagnosis. The 2001 and 2021 reports both emphasise that Griscelli syndrome is characterised by silvery hair and fair skin, and that dermatological and hair examination is critical for early diagnosis of these life-threatening disorders. The 2020 paper notes that distinguishing GS1 from GS2 is clinically challenging because both can present with neurological abnormalities, but GS2 involves immunological impairment and haemophagocytic lymphohistiocytosis, while GS1 has primary neurological dysfunction without immune deficit.
For GS1, only supportive treatment is available: pharmacological therapies to control seizures and intensive physical and mental rehabilitation to boost motor and cognitive development. The 2020 report observed that earlier diagnosis and intervention in one sibling led to better outcomes compared to her more severely affected brother. Immunotherapy and bone marrow transplantation can improve neurological and immunological features in GS2 but are not applicable to GS1. The disease is usually fatal by the first decade of life, though the 2007 case survived to age 20 without specific therapy. What remains missing are larger patient cohorts to better define the natural history, systematic genetic testing to distinguish subtypes reliably, and any clinical trials of targeted therapies — no drug has been tested for GS1. Funding for such studies, improved trial design, and better patient stratification by genotype are all lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Griscelli syndrome: A new phenotype with circumscribed pigment loss?
AbstractGriscelli syndrome is a rare genetic immunodeficiency disorder characterized by pigment dilution, recurrent cutaneous and pulmonary infections, neurological deterioration, hypogammaglobulinemia, and defective cell-mediated immunity. Mutations of three distinct genes have been described in Griscelli syndrome with different phenotypes. The disease is usually fatal by the first decade of life. We report a 20-year-old female with Griscelli syndrome with circumscribed pigment loss over thighs and abdomen in addition to diffuse pigment dilution. An accelerated phase, similar to that described in Chediak-Higashi syndrome, was also observed in our case in the form of neurological deterioration. Survival of the patient beyond the first decade of life in the absence of specific therapy was also a distinctive feature.
Clinical Case Reports · 2021 · 10 citations · open access
Griscelli Syndrome in a seven years old girl
AbstractIn this study, a case of Griscelli Syndrome (GS) in a 7 years old girl was reported. The patient initially presented with fever and pancytopenia in laboratory results; after ruling out the malignancies, she went under treatment with the diagnosis of infectious disease and was discharged after two weeks. Nevertheless, ten days after discharge, she developed new symptoms. Due to patient symptoms and general appearance, microscopic analysis of her hair shaft was done, and the abnormal distribution of pigments in the shaft was observed, indicating GS.
Canadian Review of Social Policy / Revue canadienne de politique sociale · 2001 · 8 citations
Is this as Good as it Gets? Child Care as a Test Care for Assessing the Social Union Framework Agreement
AbstractGriscelli syndrome (GS) is a rare disease that is characterized by silvery hair and fair skin. It is included in congenital grey hair syndromes, a rare group of autosomal recessive disorders characterized by silvery grey hair and severe multisystem disorders, such as immune system impairment, defects in immunological function, ocular and skeletal alterations, and nervous system defects. Herein, we report a rare case of GS type 1 and highlight the importance of a dermatological and hair examination to make an early diagnosis of these life-threatening diseases.
Dermatopathology · 2021 · 8 citations · open access
Hair Shaft Examination: A Practical Tool to Diagnose Griscelli Syndrome
AbstractGriscelli syndrome (GS) is a rare disease that is characterized by silvery hair and fair skin. It is included in congenital grey hair syndromes, a rare group of autosomal recessive disorders characterized by silvery grey hair and severe multisystem disorders, such as immune system impairment, defects in immunological function, ocular and skeletal alterations, and nervous system defects. Herein, we report a rare case of GS type 1 and highlight the importance of a dermatological and hair examination to make an early diagnosis of these life-threatening diseases.
Greater South Information System · 2020 · 0 citations · open access
Genetic analysis in three Egyptian patients with Griscelli syndrome Type 1 reveals new nonsense mutations in MYO5A
AbstractClick here for the corresponding questions to this CME article. Griscelli syndrome Type 1 (GS1; MIN 214450) is a rare autosomal recessive disease caused by mutations in the MYO5A gene.1 The syndrome was first reported in 1978,2 and since then, three subtypes have been identified according to the phenotype and gene involved. In addition to the shared common feature of silvery-grey hair and skin hypopigmentation, there are also primary neurological manifestations in GS1, immune impairment and haemophagocytic lymphohistiocytosis in GS2 (resulting from mutations in RAB27A), or hypopigmentation only in GS3 (mutations in MLPH). Elejalde syndrome (ES), also called neuroectodermal melanolysosomal disease, is characterized by silvery hair, skin hypopigmentation, ophthalmological abnormalities and severe primary neurological dysfunction with no immunological deficit. Mutations in MYO5A also cause ES, but it is still debatable whether or not GS1 and ES are distinct entities.3, 4 To date, about 20 patients with GS1, including those with ES, have been reported.5 Most of these reports have not been confirmed by genetic analysis, making accurate estimation of GS1/ES prevalence very difficult (Table S1).3 The MYO5A gene encodes the myosin Va protein, which interacts with actin to maintain molecular transport within cells. Melanosomal transport requires the integrated action of the MYO5A, RAB27A and MLPH gene products, which explains the common phenotype of pigmentary dilution among the GS subtypes.4 In addition, myosin Va is also essential for the exocytosis of certain substances such as neuropeptides from brain neurons that support synaptic activity, which can explain the neurological manifestations in GS1.6 We report three Egyptian patients – two siblings and an unrelated individual – diagnosed with GS1 (Fig. 1). All patients were born to consanguineous parents and had silvery-grey hair. They all sought medical advice in infancy with varying neurological and cutaneous manifestations (see Table 1 for full details). Following ethics approval (REC reference: 07/H0802/104) and informed consent, DNA was extracted from peripheral blood samples obtained from the probands and their parents. Sanger sequencing of all exons and splice sites of MYO5A revealed two previously unreported mutations. The two siblings (AII:2 and AII:3) were homozygous for a nonsense mutation in exon 18 (c.2110C>T; p.Gln704*), whereas Patient BII:5 was homozygous for a nonsense mutation in exon 5 (c.463C>T; p.Arg155*). Genotyping of the parents' DNA confirmed segregation of the variants, consistent with an autosomal recessive inheritance pattern (Fig. S1). GS1 is characterized by primary neurological deficits, which usually start in early infancy and include hypotonia, developmental delay, intellectual disabilities and seizures, as well as the dermatological features of silvery-grey hair and skin hypopigmentation. One challenge in clinically evaluating patients with GS who have neurological features is to exclude a diagnosis of GS2. Although individuals with GS2 characteristically develop immunological abnormalities and a poor prognosis as a result of RAB27A mutations, they may also have neurological features due to lymphocytic infiltration of the brain or haemophagocytic lymphohistiocytosis. The observation that both GS1 and GS2 can share overlapping neurological abnormalities can make a clinical distinction between the two extremely challenging, and accurate subtyping may require DNA sequencing of MYO5A and RAB27A. Immunotherapy and bone marrow transplantation can improve the neurological (and immunological) features of GS2, but for GS1, only supportive treatment is available, with pharmacological therapies offered to control seizures and intensive physical and mental rehabilitation initiated to boost motor and cognitive development. However, the potential benefits of this intensive supportive intervention were evident in Patient AII:3, for whom diagnosis and interventions started earlier than her comparatively more severely affected brother. In conclusion, clinical recognition of neurological manifestations in GS, supported by genetic testing, is important in establishing an accurate diagnosis that is relevant to treatment and prognosis. Genetic analysis of our GS1 cases expands the mutational spectrum of the disease, and provides early diagnosis and accurate genetic counselling for the families. We thank all the patients and their parents who kindly contributed their samples, and our colleagues at Alexandria University, Dr M. El-Deep and Dr Y. El-Chazli, for their kind assistance. This work was funded and supported by the UK National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) award to Guy's and St Thomas' NHS Foundation Trust, in partnership with the King's College London and King's College Hospital NHS Foundation Trust. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. To demonstrate knowledge of the underlying molecular genetic defect and clinical manifestations of Griscelli syndrome Type 1. This learning activity is freely available online at http://www.wileyhealthlearning.com/ced Once the test is passed, you will receive a certificate and the learning activity can be added to your RCP CPD diary as a self-certified entry. This activity will be available for CPD credit for 2 years following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional period.
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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