Fabry Cardiomyopathy: Current Treatment and Future Options

Vardarli, İrfan; Weber, Manuel; Rischpler, Christoph; Führer, Dagmar; Herrmann, Ken; Weidemann, Frank

doi:10.3390/jcm10143026

Cited by 12 publications

(13 citation statements)

References 70 publications

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“…Patients treated for 18 months with Migalastat showed similar trajectories as those treated with ERT and there was a durable effect to 30 months (57). Second generation ERT and substrate reduction therapy are in varying stages of clinical study and may provide further benefit in attenuating and possibly reversing disease in the FD population (55).…”

Section: Fabry Cardiomyopathymentioning

confidence: 85%

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Narrative review of pediatric heart failure in the age of precision medicine

Valikodath¹,

Godown²,

Sheybani³

2023

Transl Pediatr

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Background and Objective: Improvement in the affordability and convenience of genetic testing has rapidly expanded the understanding of the mechanistic causes of various pediatric cardiomyopathies.Concurrently, new therapies are being developed to better-target specific pathologies as opposed to classic therapies that treat the maladaptive processes of chronic heart failure. This review will discuss the advances in genetic testing and specific therapies that have been shown to benefit or potentially benefit genetically distinct subsets of the pediatric population with heart failure or at risk of developing heart failure.Methods: We undertook a comprehensive database search (January 2000-August 2022) of PubMed, utilizing terms 'pediatric', 'cardiomyopathy', 'heart failure', 'genetics', and 'precision medicine'. Additional notable studies were obtained from ClinicalTrials.gov. Studies published in English that examine genetic basis and treatment modalities of pediatric heart failure.

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Section: Fabry Cardiomyopathymentioning

confidence: 85%

“…Unfortunately, this only delays the progression of FD and most patients develop antibodies of uncertain clinical significance to the biweekly infusions (55). Chaperone therapy is a more recent option for patients with FD due to certain mutations (56).…”

Section: Fabry Cardiomyopathymentioning

confidence: 99%

Narrative review of pediatric heart failure in the age of precision medicine

Valikodath¹,

Godown²,

Sheybani³

2023

Transl Pediatr

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“…To date, the management of FD includes disease-specific therapy, as well as therapies to manage multiorgan diseases. Approved FD-specific treatments include enzyme replacement therapy (ERT) and pharmacological chaperone therapy, while other novel therapeutic approaches, such as substrate reduction therapy, gene therapy, and mRNA-based therapy, are still in development ( Table 3 ) [ 14 , 15 ]. To begin with, ERT is indicated in all symptomatic patients with an established FD diagnosis, which can delay FD advancement and reduce the burden of cardiac events when started at earlier stage [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“… Brief concepts of the pathophysiology of FD [ 14 , 15 ]. α-Gal A: α-galactosidase A, Gb3: globotriaosylceramide, lyso-Gb3: globotriaosylsphingosine, CNS: central nervous system, PNS: peripheral nervous system.…”

Section: Figurementioning

confidence: 99%

Unexplained Left Ventricular Hypertrophy with Symptomatic High-Grade Atrioventricular Block in Elderly Patients: A Case Report

Chen

2022

JCM

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Left ventricular hypertrophy (LVH) is common among older adults. Amidst all causes, Fabry disease (FD) should be considered when LVH occurs with family history, specific clinical manifestations, or cardiac alert signs. Here, we report a case of a 76-year-old male who presented late onset concentric LVH with symptomatic high-grade atrioventricular (AV) block. After dual-chamber pacemaker implantation, interrogation revealed frequent right ventricular (RV) pacing with a wide QRS duration. The patient developed heart failure symptoms with rapid deterioration of LV systolic function. Pacing-induced cardiomyopathy (PICM) was suspected, and the pacemaker was upgraded to biventricular pacing. Further FD surveys were performed, including biochemical examinations, cardiac biopsies, and genetic sequencing, and the patient was ultimately diagnosed with a cardiac variant of FD. Particularly, we strongly suggest that physiologic pacing should be initially considered for patients with FD who have symptomatic high-grade AV block, rather than traditional RV pacing to prevent PICM.

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“…Clinical manifestations of LSDs can be extremely variable depending on the type of the storage material and physical distribution throughout the body. Furthermore, disease traits can vary significantly even within the same LSD, which is particularly apparent in diseases such as Fabry, with a huge diversity of symptoms observed 7–9 . Many LSDs manifest with somatic and or neurological symptoms relatively rapidly after birth, or in rarer attenuated cases into late adulthood, although those with neurological manifestations are typically diagnosed in childhood.…”

Section: Introductionmentioning

confidence: 99%

Advances in therapies for neurological lysosomal storage disorders

Ellison

Parker

Bigger

2023

J of Inher Metab Disea

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Lysosomal Storage Disorders (LSDs) are a diverse group of inherited, monogenic diseases caused by functional defects in specific lysosomal proteins. The lysosome is a cellular organelle that plays a critical role in catabolism of waste products and recycling of macromolecules in the body. Disruption to the normal function of the lysosome can result in the toxic accumulation of storage products, often leading to irreparable cellular damage and organ dysfunction followed by premature death. The majority of LSDs have no curative treatment, with many clinical subtypes presenting in early infancy and childhood. Over two‐thirds of LSDs present with progressive neurodegeneration, often in combination with other debilitating peripheral symptoms. Consequently, there is a pressing unmet clinical need to develop new therapeutic interventions to treat these conditions. The blood–brain barrier is a crucial hurdle that needs to be overcome in order to effectively treat the central nervous system (CNS), adding considerable complexity to therapeutic design and delivery. Enzyme replacement therapy (ERT) treatments aimed at either direct injection into the brain, or using blood–brain barrier constructs are discussed, alongside more conventional substrate reduction and other drug‐related therapies. Other promising strategies developed in recent years, include gene therapy technologies specifically tailored for more effectively targeting treatment to the CNS. Here, we discuss the most recent advances in CNS‐targeted treatments for neurological LSDs with a particular emphasis on gene therapy‐based modalities, such as Adeno‐Associated Virus and haematopoietic stem cell gene therapy approaches that encouragingly, at the time of writing are being evaluated in LSD clinical trials in increasing numbers. If safety, efficacy and improved quality of life can be demonstrated, these therapies have the potential to be the new standard of care treatments for LSD patients.

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Fabry Cardiomyopathy: Current Treatment and Future Options

Cited by 12 publications

References 70 publications

Narrative review of pediatric heart failure in the age of precision medicine

Narrative review of pediatric heart failure in the age of precision medicine

Unexplained Left Ventricular Hypertrophy with Symptomatic High-Grade Atrioventricular Block in Elderly Patients: A Case Report

Advances in therapies for neurological lysosomal storage disorders

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