This is an international, multicenter, epidemiological study, which is being conducted in 5 countries (Austria, Hungary, Serbia, Spain and Poland), with a total of 500 participants to be enrolled. Targetted participants are aged between 18 and 85 years old and have a diagnosis of small fiber polyneuropathy of no obvious etiology.
The objectives of this study are to investigate the prevalence of TTR-FAP in participants with small fiber polyneuropathy of no obvious etiology and to establish biomarker/s in TTR positive cohort.
Transthyretin-related Familial Amyloid Polyneuropathy (TTR-FAP) is an autosomal dominant, progressive neurodegenerative disease, with posible fatal outcome might occur within ten years after onset. The disease is characterized by abnormal extracellular deposits of fibrillar, misfolded proteins (amyloid fibrils) in the peripheral nervous system, leading to a progressive sensory and motor polyneuropathy.
The disease is caused by mutations in the TTR gene, coding for transthyretin protein (Ttr), which functions as a carrier for the hormone thyroxine (T4) and retinol-binding protein (bound to retinol or vitamin A).
The typical presentation of TTR-FAP is a progressive sensory-motor polyneuropathy, which usually begins with loss of thermal and pain sensation in the feet, slowly ascends up the limbs and is associated with variable autonomic disturbances and extra-neurological manifestations (especially a cardiomyopathy).
The study’s goal is to investigate the prevalence of TTR-FAP disease in a cohort of 500 subjects with small fiber polyneuropathy of no obvious etiology. Participants with positive TTR mutations receive a definitive diagnosis of TTR-FAP. All identified participants will be given the opportunity to participate in one of the Biomarker studies conducted by CENTOGENE, called BioTRAP, to further detect and validate new biomarkers for TTR-FAP.
Information about the Study
Design: International, multicenter, epidemiological protocol
Study population: Participants with small fiber polyneuropathy of no obvious etiology
Number of participants: 500
First participant in: June 2018
Inclusion period: 15 months
- To investigate the prevalence of TTR-FAP in participants with small fiber polyneuropathy of no obvious etiology.
- To establish biomarker/s in TTR positive cohort.
The subjects fulfilling the eligibility criteria will be enrolled in the Study and biochemically and genetically tested for TTR-FAP. Therefore, all subjects will have a single research blood sample drawn, which will be equivalent to 30 drops (less than 1 mL). This will be applied to a CentoCard®, which will be sent to CENTOGENE and analyzed in CENTOGENE’s specialized laboratory.
In addition, past medical history and medication, family history, and physical examination findings will be recorded. All the above data will be collected on an electronic Case Report Form (eCRF).
When the CentoCard® arrives in CENTOGENE’s laboratory, full gene sequencing (Amplicon-based NGS) will be performed. In the case of a negative result, a deletion/duplication analysis (qPCR) will be conducted. These genetic tests confirm a potential TTR-FAP diagnosis.
All TTR mutation-positive blood samples will be further analyzed via mass spectrometry, in order to establish a TTR-FAP specific biomarker/s.
TTR-FAP can be inherited from biological parent/s and is caused by a mutation in the TTR gene, which codes for the transthyretin protein (Ttr). In case of a mutation in the TTR gene, a defective protein is produced, which clumps together and forms filamentous structures, called amyloid fibrils. The amyloid creates deposits in the body, that are mainly found in the nerve cells.
In the heart, the amyloid deposits can cause a restrictive cardiomyopathy, associated with high morbidity and mortality.
Treatment options for TTR-FAP include symptomatic treatment (for associated disorders), liver transplant, protein conformation stabilizers and investigational drugs.
TransThyRetin-related Familial Amyloidotic Polyneuropathy (TTR-FAP) is a disease of the peripheral nervous system that is caused by protein deposits in different tissues. The peripheral nervous system is responsible of the temperature perception, therefore the first signs of TTR-FAP are usually the loss of temperature sensation or other sensory disturbances in the feet and lower legs.
The small fiber polyneuropathy in TTR-FAP occurs from the damage to the small unmyelinated peripheral nerve fibers, whose primary roles are to innervate the skin (somatic fibers) and to help control the function of internal organs (autonomic fibers).
Informed consent is obtained from the participant
The participant is aged between 18 and 85 years
|The participant is diagnosed with small fiber polyneuropathy of no obvious etiology|
|The participant has no diagnosis of alcoholism according to International Guidelines|
|The participant has not undergone chemotherapy for carcinoma|
Inability to provide informed consent
The participant is younger than 18 years or older than 85 years
|The etiology of the small fiber polyneuropathy is clearly determined|
|The participant has a diagnosis of alcoholism according to International Guidelines|
|The participant has undergone chemotherapy for carcinoma|
Dr. Volha Skrahina, Vice Director Clinical Study Department
Am Strande 7
Dr. Snezana Skobalj, Clinical Research Associate
Am Strande 7
Sabine Rösner, Clinical Research Associate
Am Strande 7