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Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

Adams D, Tournev IL, Taylor MS, Coelho T, Planté-Bordeneuve V, Berk JL, et al.

Amyloid, 2023 Mar;30(1):1-9.
PMID: 35875890 DOI: 10.1080/13506129.2022.2091985

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy.
METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months.
RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths.
CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.
CLINICALTRIALS.GOV: NCT03759379.

Matched MeSH terms: Prealbumin/genetics
Prealbumin rather than albumin is a more sensitive indicator of acute liver disease

Yasmin MY, Aziz B, Nazim M, Madhavan RK

Malays J Pathol, 1993 Dec;15(2):147-50.
PMID: 8065177

The changes in serum prealbumin (transthyretin) and serum albumin in acute and chronic liver diseases were investigated. Albumin has long been used as a useful indicator of liver function but serum prealbumin has recently been noted for its clinical significance in acute liver diseases. Serum prealbumin concentrations and liver function tests (albumin, bilirubin, alanine aminotransferase) were determined on blood obtained from normal donors (n = 148) and from patients suffering from liver diseases (n = 78) such as acute viral hepatitis, chronic active hepatitis, cirrhosis and hepatoma. The mean serum prealbumin concentration in normal subjects was 29.6 +/- 4.82 mg/dl while the mean serum prealbumin concentration in patients with liver disease was greatly reduced (acute viral hepatitis = 15.3 +/- 7.4mg/dl; chronic active hepatitis = 10.2 +/- 6.6mg/dl; cirrhosis = 9.9 +/- 6.4mg/dl and hepatoma = 10.7 +/- 4.2). Albumin concentrations dropped slightly (13% compared to control) in acute viral hepatitis but dropped markedly (28% compared to control) in chronic liver diseases. The study suggests that serum prealbumin concentration might be a more sensitive indicator than albumin in assessing liver dysfunction in acute liver diseases.

Matched MeSH terms: Prealbumin/analysis*
Ala97Ser mutation is common among ethnic Chinese Malaysians with transthyretin familial amyloid polyneuropathy

Low SC, Tan CY, Md Sari NA, Ahmad-Annuar A, Wong KT, Lin KP, et al.

Amyloid, 2019 7 26;26(sup1):7-8.
PMID: 31343308 DOI: 10.1080/13506129.2019.1582479
Matched MeSH terms: Prealbumin/genetics*
Fulltext Tamarindus indica extract alters release of alpha enolase, apolipoprotein A-I, transthyretin and Rab GDP dissociation inhibitor beta from HepG2 cells

Chong UR, Abdul-Rahman PS, Abdul-Aziz A, Hashim OH, Junit SM

PLoS One, 2012;7(6):e39476.
PMID: 22724021 DOI: 10.1371/journal.pone.0039476

The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach.

Matched MeSH terms: Prealbumin/biosynthesis*; Prealbumin/genetics
The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile - a randomized controlled trial in middle-aged women

Rosli H, Shahar S, Rajab NF, Che Din N, Haron H

Nutr Neurosci, 2021 Mar 05.
PMID: 33666540 DOI: 10.1080/1028415X.2021.1880312

Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women.Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer.Results: There was a significant interaction effects on RAVLT immediate recall (p

Matched MeSH terms: Prealbumin