Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review

Giuffrida, Gaetano; Markovic, Uroš; Condorelli, Angelo Giuseppe; Calafiore, Valeria; Nicolosi, Daniela; Calagna, Marianna; Grasso, Stephanie; Ragusa, Marco Tindaro Valentino; Gentile, Jennifer; Napolitano, Mariasanta

doi:10.1186/s13023-023-02623-7

Cited by 16 publications

(13 citation statements)

References 71 publications

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“…Such work could provide clinicians with tools to determine which patients would benefit from Ambroxol therapy. Regarding monitoring treatment response, biomarkers used should be specific to GD, be widely available and highly sensitive, and be directly involved in the pathological pathway of GD [43].…”

Section: Discussionmentioning

confidence: 99%

The use of Ambroxol for the treatment of Gaucher disease: A systematic review

Abelleyra Lastoria,

Grewal,

Hughes

2024

eJHaem

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Gaucher disease (GD) is a heterogeneous condition requiring tailored treatment approaches. The aim of this systematic review was to synthesise and evaluate current evidence pertaining to the use of Ambroxol for the treatment of GD. Published and unpublished literature databases, conference proceedings and the reference lists of included studies were searched until 23 November 2023. A narrative synthesis was performed. Database search and risk of bias assessment were performed independently by two reviewers.Twenty‐one studies (182 patients) were included. The evidence was low in quality. Variable responses to Ambroxol were observed. Response rates were 36% and 55% in two studies reporting on type 1 GD. One study found a 22% response rate in type 2 GD, whereas another study found 29% of patients with type 3 GD reported neurological improvements. No severe adverse events were reported in the literature, with mild and reversible side effects reported. Varying response rates are to be expected (29%–100%) when treating neurological manifestations. Varying degrees of symptomatic improvement for the treatment of GD were noted in the literature. Multidisciplinary team input and clinical judgement are advised to provide personalized treatment of this complex and multi‐faceted condition.

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Section: Discussionmentioning

confidence: 99%

The use of Ambroxol for the treatment of Gaucher disease: A systematic review

Abelleyra Lastoria,

Grewal,

Hughes

2024

eJHaem

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“…As recently reviewed, [57] increased levels of Lyso‐Gb1 were also found in GCase‐associated Parkinson's disease and they are also related to the B‐cell lymphoproliferative disorders as multiple myeloma, and, also in these cases, their concentration decrease is a positive sign.…”

Section: Gaucher Diseasementioning

confidence: 91%

“…In fact, in some cases, it was even possible to detect almost normal level of this marker in stable, properly treated GD1 patients. [56] As recently reviewed, [57] increased levels of Lyso-Gb1 were also found in GCase-associated Parkinson's disease and they are also related to the B-cell lymphoproliferative disorders as multiple myeloma, and, also in these cases, their concentration decrease is a positive sign.…”

Section: Markersmentioning

confidence: 95%

“…CT, CCL18, Lyso-Gb1). [57,76] The typical SRT side effects reported during different clinical studies consist of gastrointestinal events such as diarrhea, nausea, vomiting, abdominal pain, attributable to off-target inhibition of intestinal disaccharidases, [77,78] and some neurological events including tremors, convulsion and headache. However, no other relevant secondary responses related to the impaired equilibrium of glycosphingolipids level result from the GCase inhibition (when selective), or at least not more serious than disease the SRT is used for.…”

Section: Substrate Reduction Therapymentioning

confidence: 99%

“…The clinical efficacy of SRT compared to ERT has been reviewed, indicating a similar safety profile for both therapeutic treatments and a comparable amelioration of some parameters, such as hemoglobin concentration and platelet count, liver and spleen volume and biomarkers levels ( e.g . CT, CCL18, Lyso‐Gb1) [57,76] …”

Section: Substrate Reduction Therapymentioning

confidence: 99%

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Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Prencipe,

Barzan,

Savian

et al. 2024

ChemMedChem

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Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to this class of disorders, and it is considered the most common among the Lysosomal Storage Diseases. The two main therapeutic approaches are the Enzyme Replacement Therapy (ERT) and the Substrate Reduction Therapy (SRT). ERT, consisting in replacing the defective enzyme by administering a recombinant enzyme, is effective in alleviating the visceral symptoms, hallmarks of the most common subtype of the disease whereas it has no effects when symptoms involve CNS, since the recombinant protein is unable to significantly cross the Blood Brain Barrier. The SRT strategy involves inhibiting glucosylceramide synthase (GCS), the enzyme responsible for the production of the associated storage molecule. The rational design of new inhibitors of GCS has been hampered by the lack of either the crystal structure of the enzyme or an in‐silico model of the active site which could provide important information regarding the interactions of potential inhibitors with the target, but, despite this, interesting results have been obtained and are herein reviewed.

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Gaucher disease type 3c: Expanding the clinical spectrum of an ultra‐rare disease

Wang,

Koch,

Kenney‐Jung

et al. 2024

JIMD Reports

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Gaucher disease (GD) type 3 is an autosomal recessive lysosomal disease caused by deficiency of β‐glucocerebrosidase (GCase) and encompasses a spectrum of cardiac, neurological, and ophthalmological abnormalities. Although the clinical presentations can be diverse, a recognized clinical trajectory points to an early onset, predominantly before 18 years. GD type 3c is primarily caused by homozygosity for GBA pathogenic variant c.1342G>C (p.Asp448His; historically referred to as D409H) and includes visceral, hematological, skeletal, and cardiac abnormalities. Notably, GD type 3c is distinct from other GD types because it is primarily characterized by valvular heart disease. Yet, with less than 50 patients with GD type 3c reported to date, the phenotypic spectrum and extent of cardiac involvement remains ill‐defined. We present a 20‐year‐old female with an atypical presentation of GD type 3c consisting of chronic intermediate uveitis as the presenting feature and the presence of extensive polyneuropathy starting in adolescence which has been previously unreported in GD type 3c. Distinctively, she has maintained normal cardiac function. Moreover, we compare our case with those reported in the literature to broaden awareness of the varied initial presentations of this disease. The diverse presentations seen in GD type 3c, underscored by our case and those previously reported, demonstrate the need for standardized evaluation and management protocols.

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Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review

Cited by 16 publications

References 71 publications

The use of Ambroxol for the treatment of Gaucher disease: A systematic review

The use of Ambroxol for the treatment of Gaucher disease: A systematic review

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective

Gaucher disease type 3c: Expanding the clinical spectrum of an ultra‐rare disease

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