This article explores hATTR amyloidosis, covering its causes, symptoms, genetic basis, and current treatment options. It emphasizes recent advances like FDA-approved drugs and emerging therapies aimed at reducing TTR buildup, offering hope for managing this hereditary disease.

An Overview of hATTR Amyloidosis: Origins, Manifestations, and Treatment Strategies

Globally, around 50,000 people are affected by hATTR amyloidosis, a genetic disorder inherited in an autosomal dominant pattern, meaning a person has a significant chance of inheriting the disease if one parent carries the gene.

What causes hATTR amyloidosis?
This disorder stems from the abnormal accumulation of amyloid fibrils in organs and tissues, impairing their structure and function.

This type falls under hereditary ATTR amyloidosis, a subset of six amyloidosis variants.

The disease develops due to a genetic mutation in the transthyretin (TTR) protein, primarily made in the liver. This mutation causes TTR to misfold, leading to deposits in the nervous system, heart, and digestive system, resulting in persistent symptoms. Treatments mainly focus on reducing TTR accumulation and alleviating symptoms.

Symptoms to watch for

Symptoms can differ greatly among individuals and even within families. They usually start between ages 20 and 60, depending on affected organs:

Nervous system: Numbness, tingling, wrist pain, burning sensations, loss of temperature sensation, muscle weakness.

Cardiac issues: Fatigue, dizziness, breathlessness, leg swelling, chest discomfort, abnormal heartbeats, palpitations.

Autonomic nervous system: Urinary problems, excessive sweating, dizziness when standing, sexual dysfunction, nausea, vomiting, constipation, weight loss.

Other signs include vision trouble, glaucoma, memory decline, headaches, seizures, kidney problems, strokes, and blood vessel or eye anomalies.

Current treatment options

While a cure remains unavailable, recent options include FDA-approved drugs that decrease TTR production and help manage symptoms:

Organ transplant: Replacing the liver can lower TTR levels, especially effective if done early. Challenges include organ availability, surgical risks, ongoing immune suppression, and costs.

Medications approved by the FDA: Drugs like Onpattro (patisiran) and Tegsedi (inotersen), approved in 2018, target nerve symptoms, while Vyndaqel (tafamidis), approved in 2019, addresses heart issues. These therapies aim to slow or reverse disease progression.

New therapies in development: Research includes RNA-based methods to reduce TTR production, stabilizers to prevent misfolding, and immunotherapies using monoclonal antibodies to clear deposits. These innovative options are currently under clinical evaluation.