CAMBRIDGE, Mass., ROSTOCK, Germany, BERLIN & MUNICH, Germany—Centogene N.V. and Alnylam Pharmaceuticals Inc. have kicked off a joint clinical screening program in which they will genetically screen of those at risk for hereditary transthyretin-related amyloidosis (ATTRv). This program, the hereditary TransthyRetin-related AMyloidosis and longitudinal monitoring of TTR-positive subjects (the “TRAMmoniTTR Study”), follows on the heels of the TRAM Study, which focused on epidemiological analysis for ATTRv. Under the TRAM Study, 5,000 individuals with polyneuropathy and/or cardiomyopathy of no obvious origin have been screened for ATTRv since 2017, and more than 1 percent of them eventually received an ATTRv diagnosis and were clinically characterized and regionally mapped.
“Within the initial TRAM Study, we were able to deliver truly valuable insights. More than 50 participants suffering from the known and treatable disease received the diagnosis,” noted Dr. Volha Skrahina, director of Clinical Studies at CENTOGENE. “We will now proceed with the screening in TRAMmoniTTR in order to accelerate the diagnosis for those suffering and awaiting answers. This is crucial due to the progressive nature of the disease."
This TRAMmoniTTR Study will be comprised of symptomatic and asymptomatic TTR-positive individuals who will have the opportunity to join the longitudinal phase to monitor their clinical status. Centogene has identified and characterized novel ATTRv biomarkers thanks to its metabolomics profiling platform, and will monitor these biomarkers in TTR-positive patients.
According to Prof. Peter Bauer, chief genomic officer of CENTOGENE, “This is the first study where both symptomatic and asymptomatic TTR positive participants will be monitored for two years. This will allow us to validate our ATTRv biomarkers and later utilize them for treatment individualization.”
“We are excited about expanding our collaboration with CENTOGENE in its epidemiology and biomarker work through the initiation of a new clinical program (TRAMmoniTTR) focused on Hereditary Transthyretin-Related Amyloidosis,” Dr. Bernhard Kaumanns, VP Medical Affairs CEMEA (Canada, Europe, Middle East & Africa) at Alnylam, remarked in a statement. “This program will help to better understand diagnostic pathways and identify possible biomarkers to accelerate the diagnosis of this devastating disease. Equally important is the patient follow-up that this program provides; long-term evidence-based data will be generated to improve the understanding of this disease under conditions of daily clinical practice.”
As noted by Centogene, “ATTRv is an autosomal dominant condition caused by a pathogenic variant in the TTR gene (Plante-Bordeneuve et al. 2011). The TTR gene is coding for transthyretin, formerly known as prealbumin. Transthyretin (“Ttr”) is found primarily in the serum (secreted by the liver) and the cerebrospinal fluid (secreted by the choroid plexus), and functions as a carrier for the hormone thyroxine (T4) and retinol-binding protein (bound to retinol or vitamin A).”
According to The Bridge, a website on hereditary ATTRv by Alnylam, approximately 50,000 people worldwide are believed to be affected by this condition. Centogene reports that a positive diagnosis is delayed by an average of four to five years and misdiagnoses are also possible, and as such, “In order to facilitate an early diagnosis, treatment choice and individualization, ATTRv biomarkers are critical.”