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Nephrol Dial Transplant. 2017 Jun 1;32(6):916-924. doi: 10.1093/ndt/gfw095.

Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome.

Author information

1
Clinic of Nephrology and Rheumatology, University Medicine Goettingen, Goettingen, Germany.
2
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
3
Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
4
Melbourne Health, The University of Melbourne, Parkville, VIC, Australia.
5
Division of Nephrology, Washington University School of Medicine, St Louis, MO, USA.
6
Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma de Barcelona and REDINREN, Barcelona, Spain.
7
Molecular Medicine Research Center, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
8
University of Southern California, Children's Hospital Los Angeles, Los Angeles, CA, USA.
9
Medical Genetics Unit, University of Siena, Siena, Italy.
10
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
11
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
12
Division de Néphrologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.
13
Université Paris Descartes, Paris, France.
14
Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA) Service de Néphrologie Pédiatrique, Clinique Maurice Lamy, Hôpital Necker-Enfants Malades, Paris, France.
15
Alport Syndrome Foundation, Phoenix, AZ, USA.
16
Alport Foundation of Australia, Valentine, NSW, Australia.
17
Pediatric Department, Peking University First Hospital, Beijing, China.
18
University College London-Centre for Nephrology, London, UK.
19
Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Roche Pharma Research & Early Development, Basel, Switzerland.
20
Rare Disease Group-Therapeutic Area, Global Clinical Development, Sanofi Genzyme, Naarden, The Netherlands.
21
New Indications Discovery Unit, Translational Medicine, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
22
Cardiovascular Research, Fibrosis Research, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
23
Clinical Development, Regulus Therapeutics, San Diego, CA, USA.
24
Department of Rare Diseases, Sanofi-Genzyme R&D Center, Framingham, MA, USA.
25
Discovery Biology, Shire, Lexington, MA, USA.
26
Association for Information and Research on Genetic Renal Diseases (AIRG)-France, Paris, France.
27
Federation of European Associations of patients affected by Genetic Renal Diseases, FEDERG, Brussels, Belgium.
28
Alport Israel, Israel.
29
Alport UK, Tetbury, UK.
30
Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany.
31
Renal Medicine, Royal Infirmary, University of Edinburgh, Edinburgh, UK.
32
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.

Abstract

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis.

KEYWORDS:

Alport syndrome; chronic kidney disease; guidelines; hereditary kidney disease; nephroprotection

PMID:
27190345
PMCID:
PMC5837236
DOI:
10.1093/ndt/gfw095
[Indexed for MEDLINE]
Free PMC Article

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