Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36901983", "kind": "science-record", "revision": 1, "content_hash": "sha256:a5adb8298bb91cea488a6a3a06f85365f1ca16b00aa87be464e55442ccafcbd7", "created_at": "2026-11-01T19:01:32Z", "updated_at": "2026-11-01T19:01:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.", "doi": "10.3390/ijms24054548", "pmid": "36901983", "authors": ["Ilaria Iacobucci", "Bruno Hay Mele", "Flora Cozzolino", "Vittoria Monaco", "Chiara Cimmaruta", "Maria Monti", "Giuseppina Andreotti", "Maria Monticelli"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "Enzyme replacement therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, the treatment has side effects, is costly, and requires conspicuous amounts of recombinant human protein (rh-AGAL). Thus, its optimization would benefit patients and welfare/health services (i.e., society at large). In this brief report, we describe preliminary results paving the way for two possible approaches: i. the combination of enzyme replacement therapy with pharmacological chaperones; and ii. the identification of AGAL interactors as possible therapeutic targets on which to act. We first showed that galactose, a low-affinity pharmacological chaperone, can prolong AGAL half-life in patient-derived cells treated with rh-AGAL. Then, we analyzed the interactomes of intracellular AGAL on patient-derived AGAL-defective fibroblasts treated with the two rh-AGALs approved for therapeutic purposes and compared the obtained interactomes to the one associated with endogenously produced AGAL (data available as PXD039168 on ProteomeXchange). Common interactors were aggregated and screened for sensitivity to known drugs. Such an interactor-drug list represents a starting point to deeply screen approved drugs and identify those that can affect (positively or negatively) enzyme replacement therapy.", "claims": [{"id": "claim-data-access", "statement": "The data presented in this study are available in the article and supplementary material. Proteomics data are available as PXD039168 on ProteomeXchange.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36901983", "locator": "sections[17] \"notes\" paragraph 1", "quote": "The data presented in this study are available in the article and supplementary material. 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However, th", "cal chaperone, can prolong AGAL half-life in patient-derived cells treated with rh-AGAL. Then, we analyze", "ed the interactomes of intracellular AGAL on patient-derived AGAL-defective fibroblasts treated with the", "and Methods 3.1. Cell Cultures Immortalized patient-derived fibroblasts carrying a large deletion in GLA"], "order_basis": "paper_text_order:114", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ted as previously described [32]. Cells were cultured in RPMI 1640 medium, supplemented with 10% FBS,"], "order_basis": "paper_text_order:1631", "id": "assay:2"}, {"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["five most abundant ions in each MS scan. The mass spectrometry proteomics data have been deposited in the P", "[81]. The obtained mixtures were analyzed by LC-MS/MS, using a LTQ Orbitrap XL system (Thermo Fish", "ions in each MS scan. The mass spectrometry proteomics data have been deposited in the ProteomeXcha"], "order_basis": "paper_text_order:2750", "id": "assay:3"}]}