Biomarkers and the Development of a Personalized Medicine approach in Spinal Muscular Atrophy
- 1Department of Neurology, Sydney Children’s Hospital, Australia
- 2School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Australia
- 3Brain and Mind Centre, University of Sydney, Australia
- 4Department of Neurology, Royal Children’s Hospital, Australia
Recent unprecedented advances in treatment for spinal muscular atrophy enabled patients to access the first approved disease modifying therapy for the condition. There are however many uncertainties, regarding timing of treatment initiation, response to intervention, treatment effects and long-term outcomes, which are complicated by the evolving phenotypes seen in the post-treatment era for patients with spinal muscular atrophy. Biomarkers of disease, with diagnostic, prognostic, predictive and pharmacodynamic value are thus urgently required, to facilitate a wider understanding in this dynamic landscape. A spectrum of these candidate biomarkers, will be evaluated in this review, including genetic, epigenetic, proteomic electrophysiological, and imaging measures.
Of these, SMN2 appears to be the most significant modifier of phenotype to date, and its use in prognostication shows considerable clinical utility. Longitudinal studies in patients with SMA highlight an emerging role of circulatory markers such as neurofilament, in tracking disease progression and response to treatment. Furthermore, neurophysiological biomarkers such as CMAP and MUNE values show considerable promise in the real word setting, in following the dynamic response and output of the motor unit to therapeutic intervention
The specific value for these possible biomarkers across diagnosis, prognosis, prediction of treatment response, efficacy and safety will be central to guide future patient-targeted treatments, the design of clinical trials and understanding of the pathophysiological mechanisms of disease and intervention.
Keywords: biomarker, spinal muscular atrophy, Motor unit number estimation, Compound muscle action potential, SMN2, Neurofilament
Received: 31 May 2019;
Accepted: 02 Aug 2019.
Edited by:Tim Hagenacker, Essen University Hospital, Germany
Reviewed by:Paola Sandroni, Mayo Clinic, United States
Antonio Di Muzio, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
Basil T. Darras, Boston Children's Hospital, Harvard Medical School, United States
Copyright: © 2019 Kariyawasam, D'Silva, Lin, Ryan and Farrar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Michelle A. Farrar, Department of Neurology, Sydney Children’s Hospital, Sydney, Australia, firstname.lastname@example.org