ALS and FTD : Insights into Therapeutic TargetsName : Dr. Rajka M Liscic
Affliation : Assistant Professor
University : Kepler University
Country : Australia
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The causes are still largely unknown and no effective treatment currently exists. It has been shown; however, that FTLD may coexist with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical syndrome associated with FTLD, occurs at clinical, genetic, and pathological levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43 or FUS, rarely the disease is caused by mutations in the respective genes. Frontotemporal lobar degeneration (FTLD) is genetically, neuropathologically and clinically heterogeneous and may present with behavioural, language and occasionally motor disorder, respectively. Almost all cases of ALS, as well as tau-negative FTLD share a common neuropathology, neuronal and glial inclusion bodies containing abnormal TDP-43 protein, collectively called TDP-43 proteinopathy. Recent discoveries in genetics (e.g. C9orf72 hexanucleotide expansion, the most common genetic cause of both ALS and FTD) and the subsequent neuropathological characterization have revealed remarkable overlap between ALS and FTLD-TDP indicating common pathways in pathogenesis. For ALS, an anti-glutamate agent riluzole was offered to slow disease progression (Level A), and a promising molecule, arimoclomol, is currently in clinical trials. Other compounds (e.g. neurotrophic factor (NTF) that has been implanted in mesenchymal stem cells (MSC) that produce (MSC-NTF) in patients with ALS showed to be safe, too. As new therapeutic approaches continue to emerge by targeting SOD1, TDP-43, or GRN, we present some advances that are being made in our understanding of the molecular mechanisms of these diseases, and the possibility to translate into new treatment options.
Rajka M. Liscic, MD, PhD, Ass. Professor, Kepler University Linz Medical School, Austria and 1Washington University School of Medicine, St. Louis, MO, USA; firstname.lastname@example.org