Treatment with Vyndaqel (tafamidis) or liver transplant can significantly improve the long-term outcome of patients with familial amyloid polyneuropathy (FAP) due to a common TTR mutation, researchers reported.
FAP, also known as transthyretin-related hereditary amyloidosis (hATTR), is a rare disease caused by genetic mutations in the TTR gene. These mutations are often associated with transthyretin amyloidosis, which is characterized by the accumulation of transthyretin protein in the liver, the eye’s retina, and nerve cells.
With no cure available, liver transplant and treatment with Vyndaqel are the only strategies that can be used to modify the course of this life-threatening, progressive disease.
Liver transplants have been used since 1990 to treat these patients. The approach uses the new liver’s healthy genes to prevent the production of additional amyloid deposits, which slows the disease’s progression and prolongs survival.
More recently, Vyndaqel was approved as a disease-modifying agent, as it can stabilize TTR proteins and prevent the formation of damaging aggregates. Despite Vyndaqel’s demonstrated efficacy, its long-term therapeutic effect has been seen to decline in FAP patients at different stages of the disease.
In a study titled “Hereditary amyloidosis related to transthyretin V30M (hATTR V30M): disease progression in treated and untreated patients,” Portuguese researchers evaluated the long-term impact of these two treatment strategies. The study was published in the European Journal of Neurology.
The team evaluated the clinical course of FAP patients with the Val30Met mutation, the most common variant of the TTR gene, upon treatment with Vyndaqel or liver transplant for three years.
The study included 81 patients who were followed between 1990 and 2013 at a single clinical center. A total of 27 patients received no treatment, while 25 had liver transplants, and 29 were treated with Vyndaqel.
All treated patients showed signs of stable disease, which remained in stage I (with mild symptoms affecting the lower limbs) during the three-year period of follow-up. In contrast, 18.5 percent of patients who received no treatment progressed to stage II (with moderate symptoms and further nerve damage and in need of ambulatory aid) during the same period.
These clinical differences were further evidenced by the progressively worse disability scores of untreated patients over time, as measured by the modified polyneuropathy disability score (mPND). In the treated groups, the disability scores remained relatively stable over three years, with 80-90 percent of patients obtaining an mPND score of I.
Untreated patients showed worse progressive nerve cell damage, affecting both the sensory and motor nervous system. Those who underwent liver transplant had the lowest rate of nerve cell damage progression, followed by patients taking Vyndaqel.
A more detailed analysis revealed that about 41.4 percent of the patients treated with Vyndaqel did not respond to treatment. When researchers excluded these patients from the analysis they found no significant difference between the two groups of treated patients.
The progressive deterioration of sensory nerve cells in Vyndaqel-treated patients was found to be similar to that of transplanted patients, whereas those who did not respond to treatment showed a significantly faster progression.
Collectively, these results demonstrated that either liver transplant or Vyndaqel can similarly prevent FAP progression in responsive patients.
“Both liver transplant and tafamidis [Vyndaqel] therapy modify the natural history of hATTR V30M by reducing neuropathy [nerve damage] progression,” the researchers stated.