https://repositorio.fleni.org.ar/xmlui/handle/123456789/21 2026-04-09T10:20:00Z 2026-04-09T10:20:00Z Sarandría, María Eugenia Rey, Roberto D. De Rosa, Rodrigo Corbalán, Vanesa Mesa, Lilia https://repositorio.fleni.org.ar/xmlui/handle/123456789/1297 2025-01-06T16:50:18Z 2024-01-01T00:00:00Z

Duchenne muscular distrophy in Tafí del Valle, Tucumán, Argentina. Sarandría, María Eugenia; Rey, Roberto D.; De Rosa, Rodrigo; Corbalán, Vanesa; Mesa, Lilia Introduction: Duchenne muscular dystrophy (DMD) is an inherited, X-linked neuromuscular disorder with a global cumulative prevalence of 7.1 cases every 100 000 males. A relationship between consanguinity and DMD has been reported. We aimed to describe the prevalence and the sociodemographic, clinical and genetic characteristics of patients with DMD in an isolated population in Tafí del Valle (Tucumán, Argentina). Materials and methods: Cross-sectional, descriptive, epidemiological study. Demographic, clinical and genetic data were retrieved from medical records. Pedigree charts were made after an interview with the family group. Results: Seven male patients with DMD of DiaguitaCalchaquí ethnicity were identified (median age: 14 years old), with a prevalence of 0.12%. Five different mutations were reported. No consanguinity was identified in pedigree charts. Discussion: An unusual high prevalence of DMD was identified in Tafí del Valle. . In addition, there are 5 different mutations in seven patients suggesting a high number of mutations “de novo”.

2024-01-01T00:00:00Z Khella, Sami Marques, Wilson Chao, Chi-Chao Yesim Parman, Fatma Franca, Marcondes C. Guo, Yuh-Cherng Ro, Long-Sun Calandra, Cristian R. Kowacs, Pedro A. Berk, John L. Piera Obici, Laura Barroso, Fabio Adrián Conceição, Isabel Schneider, Eugene Viney, Nicholas J. Dyck, P. James B. Waddington Cruz, Marcia Coelho, Teresa https://repositorio.fleni.org.ar/xmlui/handle/123456789/1137 2025-01-03T15:52:41Z 2023-04-24T00:00:00Z

Eplontersen in Hereditary ATTR-polyneuropathy: Week 66 Final Analysis of the Phase 3 NEURO-TTRansform Study Khella, Sami; Marques, Wilson; Chao, Chi-Chao; Yesim Parman, Fatma; Franca, Marcondes C.; Guo, Yuh-Cherng; Ro, Long-Sun; Calandra, Cristian R.; Kowacs, Pedro A.; Berk, John L.; Piera Obici, Laura; Barroso, Fabio Adrián; Conceição, Isabel; Schneider, Eugene; Viney, Nicholas J.; Dyck, P. James B.; Waddington Cruz, Marcia; Coelho, Teresa Background ATTRv-PN is a rare, progressive, and debilitating disease caused by accumulation of amyloid fibrils composed of transthyretin (TTR) protein in multiple organ systems. Eplontersen, a ligand-conjugated antisense oligonucleotide that inhibits TTR protein synthesis, is being assessed in the NEURO-TTRansform study. Previously reported topline statistics established that the coprimary endpoints and key secondary endpoint were met at the prespecified Week 35 interim analysis. Eplontersen treatment resulted in significant reductions in serum TTR concentration and neuropathy impairment (modified Neuropathy Impairment Score +7 [mNIS+7]), and improved quality of life (Norfolk Quality of Life-Diabetic Neuropathy score [Norfolk QoL-DN]), compared with external placebo (from the NEURO-TTR study [NCT01737398]). Eplontersen treatment also demonstrated an acceptable safety and tolerability profile. Objective To evaluate the final efficacy and safety analysis of eplontersen at Week 66 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, open-label NEURO-TTRansform study (NCT04136184). Design/Methods NEURO-TTRansform enrolled 168 adults with ATTRv-PN, defined by Coutinho Stage 1?2, a documented TTR sequence variant, and signs/symptoms consistent with polyneuropathy (Neuropathy Impairment Score ≥10 and ≤130). Patients were assigned 6:1 to eplontersen 45 mg subcutaneously every 4 weeks (n=144) or inotersen 300 mg once weekly (n=24) until the prespecified Week 35 interim analysis, after which all patients received eplontersen 45 mg subcutaneously every 4 weeks. All patients who received eplontersen were compared with an external placebo group from the NEURO-TTR study at Week 66. Coprimary efficacy assessments at Week 66 included serum TTR concentration, mNIS+7, and the Norfolk QoL-DN score. Safety and tolerability were also assessed. Results Full results from the efficacy and safety analysis at Week 66 and Week 35 will be presented. Conclusions Results from the final analysis at Week 66 will provide detailed longer-term data on the efficacy and safety of eplontersen in patients with Stage 1 or 2 ATTRv-PN.

2023-04-24T00:00:00Z Gentile, Luca Coelho, Teresa Dispenzieri, Angela Conceição, Isabel Waddington Cruz, Marcia Kristen, Arnt V. Wixner, Jonas Diemberger, Igor Gonzalez-Moreno, Juan Cariou, Eve Maurer, Mathew S. Planté-Bordeneuve, Violaine Garcia-Pavia, Pablo Tournev, Ivailo Gonzalez-Costello, Jose Gonzalez Duarte, Alejandra Grogan, Martha Mazzeo, Anna THAOS investigators Barroso, Fabio Adrián https://repositorio.fleni.org.ar/xmlui/handle/123456789/1126 2024-07-22T14:04:56Z 2023-11-10T00:00:00Z

A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS) Gentile, Luca; Coelho, Teresa; Dispenzieri, Angela; Conceição, Isabel; Waddington Cruz, Marcia; Kristen, Arnt V.; Wixner, Jonas; Diemberger, Igor; Gonzalez-Moreno, Juan; Cariou, Eve; Maurer, Mathew S.; Planté-Bordeneuve, Violaine; Garcia-Pavia, Pablo; Tournev, Ivailo; Gonzalez-Costello, Jose; Gonzalez Duarte, Alejandra; Grogan, Martha; Mazzeo, Anna; THAOS investigators; Barroso, Fabio Adrián Background: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs. Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry. Results: This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5). Conclusions: This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.

2023-11-10T00:00:00Z Gonzalez-Moreno, Juan Dispenzieri, Angela Grogan, Martha Coelho, Teresa Tournev, Ivailo Waddington Cruz, Marcia Wixner, Jonas Diemberger, Igor Garcia-Pavia, Pablo Chapman, Doug Gupta, Pritam Glass, Oliver Amass, Leslie THAOS investigators Barroso, Fabio Adrián https://repositorio.fleni.org.ar/xmlui/handle/123456789/1055 2024-07-22T14:05:06Z 2023-12-20T00:00:00Z

Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey Gonzalez-Moreno, Juan; Dispenzieri, Angela; Grogan, Martha; Coelho, Teresa; Tournev, Ivailo; Waddington Cruz, Marcia; Wixner, Jonas; Diemberger, Igor; Garcia-Pavia, Pablo; Chapman, Doug; Gupta, Pritam; Glass, Oliver; Amass, Leslie; THAOS investigators; Barroso, Fabio Adrián Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1-2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis.

2023-12-20T00:00:00Z