Familial Amyloid Polyneuropathy
Also known as: FAP, Transthyretin Amyloidosis, ATTRv Amyloidosis, Hereditary Amyloid Neuropathy
Familial Amyloid Polyneuropathy (FAP) is a rare, progressive, and inherited disorder caused by mutations in the transthyretin (TTR) gene. These mutations lead to the misfolding and aggregation of TTR protein, forming amyloid fibrils that deposit in various tissues and organs, primarily affecting the peripheral nerves, heart, and gastrointestinal tract. This deposition causes nerve damage, leading to sensory, motor, and autonomic dysfunction.
Imagine your body makes a protein that's supposed to help, but it gets folded wrong and clumps together. These clumps stick to your nerves and heart, causing them to not work properly. It's like having sticky stuff clogging up the wires and pipes in your body. Doctors can give you medicine to stop the protein from clumping or even replace the part of your body that's making the bad protein.
Signs & Symptoms
- Progressive peripheral neuropathy
- Sensory loss (pain, temperature)
- Motor weakness
- Autonomic dysfunction (orthostatic hypotension, bowel irregularities, urinary problems)
- Cardiac involvement (cardiomyopathy, arrhythmias)
- Gastrointestinal issues (diarrhea, constipation, nausea, vomiting)
- Carpal tunnel syndrome
- Visual impairment (vitreous opacities)
- Weight loss
- Kidney involvement
Treatment Options
Tafamidis
MODERATELY EFFECTIVE Approved 2019Patisiran
HIGHLY EFFECTIVE Approved 2018Inotersen
MODERATELY EFFECTIVE Approved 2018Liver Transplantation
MODERATELY EFFECTIVEDiflunisal
MODERATELY EFFECTIVESupportive Care
SUPPORTIVEDiagnosis
- Clinical evaluation
- Neurological examination
- Genetic testing for TTR mutations
- Nerve biopsy with amyloid staining
- Cardiac evaluation (ECG, echocardiogram, MRI)
- Serum and urine TTR levels
- SAP scan
- ATTR scintigraphy
History
FAP was first described in Portugal in the 1950s by Dr. Corino de Andrade. Initially, liver transplantation was the only available treatment option. The discovery of TTR as the causative protein and subsequent development of TTR stabilizers and gene silencing therapies have revolutionized the treatment landscape.
Recent Breakthroughs
FDA Approves Patisiran for hATTR Amyloidosis
Patisiran, an RNA interference therapeutic, received FDA approval for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR), marking a significant advancement in targeted gene therapy for this condition.
FDA Approves Inotersen for hATTR Amyloidosis
Inotersen, an antisense oligonucleotide, was approved by the FDA for the treatment of hATTR amyloidosis, providing another option for reducing TTR protein production.
FDA Approves Tafamidis for hATTR Amyloidosis Cardiomyopathy
Tafamidis received FDA approval for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), expanding its use beyond polyneuropathy and addressing the cardiac manifestations of the disease.
Vutrisiran Approved for hATTR Amyloidosis
Vutrisiran, a next-generation RNAi therapeutic, was approved for hATTR amyloidosis, offering subcutaneous administration and potentially improved efficacy and safety profiles compared to earlier treatments.