Familial Amyloid Neuropathy

Watchlist

(log in to enable)

Retrieved

2021-01-18

Source

Wikipedia

Trials

—

Genes

TTR, FAP, GSN, APP, B2M, APOA1, CRP, MMP9, SERPINA1, PRNP, RBP4, SAA1, SAA2, ATXN2, SST

Drugs

3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid, Doxycycline hyclate, Eprodisate

3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid, Doxycycline hyclate, Eprodisate, Patisiran ( Onpattro ), Phosphorothioate oligonucleotide targeted to transthyretin ( TEGSEDI ), Revusiran, Tafamidis ( VYNDAQEL ), synthetic double-stranded siRNA oligonucleotide targeted against transthyretin mRNA, with six phosphorothioate linkages in the backbone, and nine 2'-fluoro and thirty-five 2'-O-methyl nucleoside residues in the sequence, which is covalently linked via a phosphodiester group to a ligand containing three N-acetylgalactosamine residues

Interested in hearing about new therapies?

The familial amyloid neuropathies (or familial amyloidotic neuropathies, neuropathic heredofamilial amyloidosis, familial amyloid polyneuropathy) are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.

Classification

The aggregation of one precursor protein leads to peripheral neuropathy and/or autonomic nervous system dysfunction. These proteins include: transthyretin (ATTR, the most commonly implicated protein), apolipoprotein A1, and gelsolin.

Due to the rareness of the other types of familial neuropathies, transthyretin amyloidogenesis-associated polyneuropathy should probably be considered first.

"FAP-I" and "FAP-II" are associated with transthyretin. (Senile systemic amyloidosis [abbreviated "SSA"] is also associated with transthyretin aggregation.)

"FAP-III" is also known as "Iowa-type", and involves apolipoprotein A1.

"FAP-IV" is also known as "Finnish-type", and involves gelsolin.

Fibrinogen, apolipoprotein A1, and lysozyme are associated with a closely related condition, familial visceral amyloidosis.

Diagnosis is confirmed by blood tests, organ biopsies, and tissue biopsies. Genetic testing can also be used to confirm a mutation in the TTR gene. Although some people with a hATTR gene mutation may not experience symptoms.

Treatment

Liver transplantation has proven to be effective for ATTR familial amyloidosis due to Val30Met mutation.

In 2011 the European Medicines Agency approved tafamidis for this condition. The FDA rejected the application for marketing approval in the US in 2012 on the basis that the clinical trial data did not show efficacy based on a functional endpoint, and the FDA requested further clinical trials.