title: Clinical Trials in Spinal and Bulbar Muscular Atrophy-Past, Present, and Future.
abstract: Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy's disease, is a rare adult-onset lower motor neuron disorder with a classic X-linked inheritance pattern. It is caused by the abnormal expansion of the CAG-repeat tract in the androgen receptor gene. Despite important progress in the understanding of the molecular pathogenesis and the availability of a broad set of model organisms, successful translation of these insights into clinical interventions remains elusive. Here we review the available information on clinical trials in SBMA and discuss the challenges and pitfalls that impede therapy development. Two important factors are the variability of the complex neuro-endocrinological phenotype and the comparatively low incidence of the disease that renders recruitment for clinical trials demanding. We propose that these challenges can be and need to be overcome by fostering closer collaborations between clinical research centers, the patient communities and the industry and non-industry sponsors of clinical trials.
authors.affiliation: Clinic of Neurology, Ulm University, Ulm, 89081, Germany. patrick.weydt@uni-ulm.de.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0003-2344-5662
authors.initials: P
authors.lastname: Weydt
authors.affiliation: Department of Clinical Neurosciences, Clinic of Central and Peripheral Degenerative Neuropathies Unit, IRCCS Foundation, "C. Besta" Neurological Institute, Via Celoria 11, Milan, 20133, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sagnelli
authors.affiliation: Clinic of Neurology, Ulm University, Ulm, 89081, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Rosenbohm
authors.affiliation: Centre for Neuromuscular Diseases and Sobell Department for Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, F-75013, France.|Département des Maladies du Système Nerveux, APHP Hôpital Pitié-Salpêtriere, Centre référent SLA, Paris, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.affiliation: Clinic of Neurology, Ulm University, Ulm, 89081, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Clinical Neurosciences, Clinic of Central and Peripheral Degenerative Neuropathies Unit, IRCCS Foundation, "C. Besta" Neurological Institute, Via Celoria 11, Milan, 20133, Italy. davide.pareyson@istituto-besta.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D006801:Humans; D009465:Neuromuscular Agents / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D009465:Neuromuscular Agents
keywords: Clinical trials; Kennedy disease; Spinal and bulbar muscular atrophy; Therapy development