Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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The investigational monoclonal antibody PRX004 is designed to specifically target and deplete TTR amyloid. Here, we report on the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of PRX004 in patients with ATTRv amyloidosis. ⋯ PRX004 was well tolerated in patients with ATTRv amyloidosis and demonstrated potential clinical activity. A phase 2 randomised controlled trial in ATTR cardiomyopathy is ongoing (NCT05442047).
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AA amyloidosis is a prototypic example of systemic amyloidosis: it results from the prolonged overproduction of SAA protein produced in response to chronic inflammation. AA amyloidosis primarily affects the kidneys, liver, spleen, gastrointestinal tract, leading to a variety of symptoms. First, this review examines AA amyloidosis in humans, focusing on pathogenesis, clinical presentation, and diagnosis and then in animals. ⋯ Finally, biochemical and structural data on native SAA and on AA amyloid fibrils from human, murine, and cat ex vivo samples are discussed. The available structural data depict a complex scenario, where SAA can misfold forming highly different amyloid assemblies. This review highlights the complexity of AA amyloidosis, emphasising the need for further research into its spread in the animal kingdom, its structural aspects, and pathogenetic mechanisms to evaluate its impact on human and animal health.