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Suhr, O. B., Wixner, J., Anan, I., Lundgren, H.-E., Wijayatunga, P., Westermark, P. & Ihse, E. (2019). Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families. PLoS ONE, 14(2), Article ID e0211983.
Open this publication in new window or tab >>Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0211983Article in journal (Refereed) Published
Abstract [en]

Background: The amyloid fibril in hereditary transthyretin (TTR) Val30Met (pVal50Met) amyloid (ATTR Val30Met) amyloidosis is composed of either a mixture of full-length and TTR fragments (Type A) or of only full-length TTR (Type B). The type of amyloid fibril exerts an impact on the phenotype of the disease, and on the outcome of diagnostic procedures and therapy. The aim of the present study was to investigate if the type of amyloid fibril remains the same within ATTR Val30Met amyloidosis families. Methods: Fifteen families were identified in whom at least two first-degree relatives had their amyloid fibril composition determined. The type of ATTR was determined by Western blot in all but two patients. For these two patients a positive 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy indicated ATTR Type A. Results: In 14 of the 15 families, the same amyloid fibril composition was noted irrespective of differences in age at onset. In the one family, different ATTR fibril types was found in two brothers with similar ages at onset. Conclusions: Family predisposition appears to have an impact on amyloid fibril composition in members of the family irrespective of their age at onset of disease, but if genetically determined, the gene/genes are likely to be situated at another location than the TTR gene in the genome.

Place, publisher, year, edition, pages
Public Library Science, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-157583 (URN)10.1371/journal.pone.0211983 (DOI)000459806400043 ()30811423 (PubMedID)
Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-04-01Bibliographically approved
Suhr, O. B. (2019). Commentary to Isabel Conceicao et al. early diagnosis through targeted follow-up of identified carriers of TTR gene mutations. Amyloid: Journal of Protein Folding Disorders, 26(1), 1-2
Open this publication in new window or tab >>Commentary to Isabel Conceicao et al. early diagnosis through targeted follow-up of identified carriers of TTR gene mutations
2019 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, no 1, p. 1-2Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-158974 (URN)10.1080/13506129.2018.1558051 (DOI)000465229800001 ()30806514 (PubMedID)
Available from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-05-27Bibliographically approved
Solomon, S. D., Adams, D., Kristen, A., Grogan, M., Gonzalez-Duarte, A., Maurer, M. S., . . . Suhr, O. B. (2019). Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study. Circulation, 139(4), 431-443
Open this publication in new window or tab >>Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 4, p. 431-443Article in journal (Refereed) Published
Abstract [en]

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed.

Methods: APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness 13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis.

Results: In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference SEM: -0.90.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3 +/- 3.9 mL, P=0.036), decreased global longitudinal strain (-1.4 +/- 0.6%, P=0.015), and increased cardiac output (0.38 +/- 0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01).

Conclusions: Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
APOLLO, cardiac amyloidosis, cardiomyopathy, hATTR amyloidosis, patisiran, RNA interference
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-157226 (URN)10.1161/CIRCULATIONAHA.118.035831 (DOI)000459430400004 ()30586695 (PubMedID)
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-03-20Bibliographically approved
Grogan, M., Hawkins, P. N., Kristen, A. V., Berk, J. L., Suhr, O. B., Lin, H., . . . Judge, D. P. (2019). Identifying Mixed Phenotype: Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy. Paper presented at 23rd Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA), SEP 13-16, 2019, Philadelphia, PA. Journal of Cardiac Failure, 25(8), S9-S10
Open this publication in new window or tab >>Identifying Mixed Phenotype: Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy
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2019 (English)In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 25, no 8, p. S9-S10Article in journal, Meeting abstract (Other academic) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-163696 (URN)10.1016/j.cardfail.2019.07.031 (DOI)000482698000025 ()
Conference
23rd Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA), SEP 13-16, 2019, Philadelphia, PA
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-16Bibliographically approved
Ajroud-Driss, S., Adams, D., Coelho, T., Polydefkis, M., Gonzalez-Duarte, A., Quan, D., . . . Suhr, O. B. (2019). Impact of Patisiran on Overall Health Status in hATTR Amyloidosis: Results from the APOLLO Trial. Paper presented at 71st Annual Meeting of the American-Academy-of-Neurology (AAN), MAY 04-10, 2019, Philadelphia, PA. Neurology, 92(15)
Open this publication in new window or tab >>Impact of Patisiran on Overall Health Status in hATTR Amyloidosis: Results from the APOLLO Trial
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2019 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 15Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-162024 (URN)000475965906204 ()
Conference
71st Annual Meeting of the American-Academy-of-Neurology (AAN), MAY 04-10, 2019, Philadelphia, PA
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Suhr, O. B. (2019). Response: concerning "late early and late onset" ATTR Val30Met patients. Amyloid: Journal of Protein Folding Disorders
Open this publication in new window or tab >>Response: concerning "late early and late onset" ATTR Val30Met patients
2019 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818Article in journal, Editorial material (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
Taylor & Francis, 2019
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-164048 (URN)10.1080/13506129.2019.1642192 (DOI)000488109000001 ()31554437 (PubMedID)
Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2019-10-15
Unéus, E., Wilhelmsson, C., Suhr, O., Anan, I., Wixner, J., Pilebro, B., . . . Sundström, T. (2019). Visualisation of amyloid deposition within the brain of long-term hereditary transthyretin amyloidosis survivors by 18F-flutemetamol positron emission tomography. Paper presented at 5th Congress of the European Academy of Neurology (EAN), June 29 – July 2, 2019, Oslo, Norway. European Journal of Neurology, 26(S1), 287-287, Article ID EPR3027.
Open this publication in new window or tab >>Visualisation of amyloid deposition within the brain of long-term hereditary transthyretin amyloidosis survivors by 18F-flutemetamol positron emission tomography
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2019 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no S1, p. 287-287, article id EPR3027Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background and aims: Hereditary transthyretin amyloid (ATTRv) amyloidosis caused by the transthyretin (TTR) Val30Met (p.V50M) mutation is characterised by peripheral neuropathy, and central nervous (CNS) complications has rarely been reported. However, liver transplantation has prolonged the patients’ survival, and CNS complications attributed to amyloid angiopathy caused by CNS synthesis of variant TTR have been reported. The aim of the study was to ascertain CNS amyloid deposition in long-term ATTRv survivors.

Methods: 20 ATTR Val30Met patients with symptoms from the CNS and a median disease duration of 16 years (9-25 years) together with five Alzheimer (AD) patients, who served as positive controls were included in the study. Amyloid CNS deposits were assessed by 18F- flutemetamol PET/CT examination utilising relative z scores with pons as reference.

Results: Expectedly, all Alzheimer patients had an clearly increased global composite z score above 2.0 compared with 55% of the ATTRv patients. There was an increased local uptake corresponding to cerebellum in 12 ATTRv patients compared to only one in the AD group (fig 1). Four of these ATTRv patients had a global composite z score within the normal range. No correlation between duration after 9 years and amyloid CNS deposition was noted.

Conclusion: Amyloid deposition within the brain after long-standing ATTRv amyloidosis is increased and is often noted in the cerebellum. However, not all patient display amyloid CNS deposition, thus, additional causes for CNS complications should always be considered.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-161913 (URN)10.1111/ene.14018 (DOI)000474481001092 ()
Conference
5th Congress of the European Academy of Neurology (EAN), June 29 – July 2, 2019, Oslo, Norway
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-11-28Bibliographically approved
Wange, N., Anan, I., Ericzon, B.-G., Pennlert, J., Pilebro, B., Suhr, O. B. & Wixner, J. (2018). Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients. Transplantation, 102(2), e59-e66
Open this publication in new window or tab >>Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients
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2018 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, no 2, p. e59-e66Article in journal (Refereed) Published
Abstract [en]

Background. Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. Methods. The medical records of all LTx ATTRm amyloidosis patients in the county of Vasterbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. Results. Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029). Conclusions. AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-144941 (URN)10.1097/TP.0000000000001975 (DOI)000424093400004 ()29019809 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2019-05-21Bibliographically approved
Gonzalez-Duarte, A., Adams, D., O'Riordan, W., Yang, C.-C., Yamashita, T., Kristen, A., . . . Suhr, O. (2018). Changes in neuropathy stage in patients with hATTR amyloidosis following patisiran treatment: Analysis from APOLLO. Paper presented at Annual Meeting of the Peripheral-Nerve-Society, JUL 21-25, 2018, Baltimore, MD. Journal of the peripheral nervous system, 23(4), 400-400
Open this publication in new window or tab >>Changes in neuropathy stage in patients with hATTR amyloidosis following patisiran treatment: Analysis from APOLLO
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2018 (English)In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 23, no 4, p. 400-400Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
Other
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-154830 (URN)000452787700372 ()
Conference
Annual Meeting of the Peripheral-Nerve-Society, JUL 21-25, 2018, Baltimore, MD
Available from: 2019-02-28 Created: 2019-02-28 Last updated: 2019-02-28Bibliographically approved
Ajroud-Driss, S., Adams, D., Coelho, T., Polydefkis, M., Gonzalez-Duarte, A., Quan, D., . . . Suhr, O. B. (2018). Impact of Patisiran on overall health status in hATTR amyloidosis: Results from the APOLLO trial. Paper presented at Annual Meeting of the Peripheral-Nerve-Society, JUL 21-25, 2018, Baltimore, MD. Journal of the peripheral nervous system, 23(4), 272-273
Open this publication in new window or tab >>Impact of Patisiran on overall health status in hATTR amyloidosis: Results from the APOLLO trial
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2018 (English)In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 23, no 4, p. 272-273Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
Other
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-154832 (URN)000452787700060 ()
Conference
Annual Meeting of the Peripheral-Nerve-Society, JUL 21-25, 2018, Baltimore, MD
Note

Meeting Abstract: 55

Available from: 2019-02-28 Created: 2019-02-28 Last updated: 2019-02-28Bibliographically approved
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