Novel Therapeutic Approaches in Inherited Neuropathies: A Systematic Review

Abstract

The management of inherited neuropathies relies mostly on the treatment of symptoms. In recent years, a better understanding of the pathogenic mechanisms that underlie neuropathies has allowed for the development of disease-modifying therapies. Here, we systematically review the therapies that have emerged in this field over the last five years. An updated list of diseases with peripheral neuropathy as a clinical feature was created based on panels of genes used clinically to diagnose inherited neuropathy. This list was extended by an analysis of published data by the authors and verified by two experts. A comprehensive search for studies of human patients suffering from one of the diseases in our list yielded 28 studies that assessed neuropathy as a primary or secondary outcome. Although the use of various scales and scoring systems made comparisons difficult, this analysis identified diseases associated with neuropathy for which approved therapies exist. An important finding is that the symptoms and/or biomarkers of neuropathies were assessed only in a minority of cases. Therefore, further investigation of treatment efficacy on neuropathies in future trials must employ objective, consistent methods such as wearable technologies, motor unit indexes, MRI or sonography imaging, or the use of blood biomarkers associated with consistent nerve conduction studies.

The Importance of Early Treatment of Inherited Neuromuscular Conditions

“…It should be noted that for certain neuromuscular diseases, potential therapies are currently in development or undergoing clinical trials, but they have not yet received approval for clinical use. These diseases include X-linked myotubular myopathy, centronuclear myopathy [ 2 ], nemaline myopathy [ 3 ], limb-girdle dystrophy [ 4, 5 ], thymidine kinase 2 deficiency [ 6 ] and various other neuropathies [ 7 ]. Moreover, the significance of timely treatment has not been adequately addressed for certain drugs already available in clinical practice.…”