Browsing by Author "Raal, Frederick Johan"

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    Familial Hypercholesterolaemia: three decades of advances in therapy
    (2022) Raal, Frederick Johan
    Severe familial hypercholesterolaemia (FH), particularly homozygous FH (HoFH), remains a difficult condition to treat. As a result of markedly elevated low density lipoproteincholesterol (LDL-C) levels from conception, subjects with severe FH suffer from accelerated, premature atherosclerotic cardiovascular disease often resulting in premature death. However, there have been remarkable advances in treatment for this condition and this thesis describes the advances in therapy for FH over the past three decades. Lipid lowering therapies which act mainly by up regulating LDL receptor (LDLR) function, such as high intensity statin, ezetimibe and PCSK9-inhibitors, form the backbone of treatment. This combination is often sufficient to attain LDL-C targets in the majority of subject with heterozygous FH (HeFH). However, a small percentage of HeFH and the vast majority of HoFH patients are unable to achieve acceptable LDL-C levels even with this combination therapy. The addition of therapies that are independent of LDLR function, such as lomitapide and, more recently, the ANGPTL3 inhibitor, evinacumab, are required. These therapies have reduced the need for lipoprotein apheresis which is now only required for the most severe cases, particularly for those HoFH patients with minimal or no residual LDLR function. Prospects for gene therapy are promising. However, despite substantial progress, several technical issues still need to be resolved before this therapy can be safely and effectively applied. Overcoming the challenges of severe FH has been a long and difficult journey, but with the treatment options now available, the future for severe FH looks bright.