<p>The purpose of the current study was to determine whether implementing EMST through telepractice is feasible and effective for providing better respiratory support to improve or maintain communication and cough production in ALS. In a nine-week multiple baseline design, twelve participants with mild ALS completed six weeks of Expiratory Muscle Strength Training (EMST) at a moderate intensity level. Descriptive data revealed that it is feasible for speech-language pathologists to implement EMST through telepractice with individuals who have ALS, as minimal time and caregiver involvement was required to implement EMST successfully and adherence and attendance rates were high. EMST implemented through telepractice resulted in a significant increase in maximum expiratory pressure (MEP) at the group level. At the individual level, nine participants had significant increases in MEP, two participants MEP remained stable, and one participant’s MEP decreased Post-Training, most likely due to poor adherence. These overall improvements to MEP did not result in significant improvements to respiratory-dependent speech outcome measures such as pause frequencies and pause durations at the group level. A lack of significant changes to the respiratory-dependent speech outcome measures, but a significant declination in the control variable of articulation rate that is not dependent on the respiratory system suggests that EMST had a maintenance effect for most participants. At the individual level, EMST appears to impact neural control of speech as it alters the pause patterns uniquely for each participant, with some participants demonstrating improvements and others demonstrating maintenance or declination. Maintenance at the group level was also observed for cough strength following EMST. In conclusion, EMST can be implemented via telepractice with people who have mild ALS and may help people with ALS maintain speech and cough production by altering respiratory support. </p>

Amyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disorder characterised by selective loss of upper and lower motor neurons (MNs). Recently, the GGGGCC (G4C2) hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) has been identified as the most common genetic cause of ALS, highlighting the importance of studying the pathogenic mechanisms underlying this mutation. Accumulating evidence implicates that ALS is a multisystem and multifactor disease. Specifically, non-neuronal cells, astrocytes in particular, are also affected by toxicity mediated by ALS-related mutations, and they can contribute to neurodegeneration, suggesting astrocytes as a key player in ALS pathogenesis. Here, a human induced pluripotent stem cells (iPSCs)-based in vitro model of ALS was established to investigate the impact of the C9orf72 mutation on astrocyte behaviour—both cell- and non-cell autonomous. Work in this study shows that patient iPSC-derived astrocytes recapitulate key pathological features associated with C9orf72-mediated ALS, such as formation of G4C2 repeat RNA foci, production of dipeptide repeat (DPR) proteins and reduced viability under basal conditions compared to controls. Moreover, C9orf72 mutant astrocytes in co-culture result in reduced viability and structural defects of human MNs. Importantly, correction of the G4C2 repeat expansion in mutant astrocytes through targeted gene editing reverses these phenotypes, strongly confirming that the C9orf72 mutation is responsible for the observed findings. Altogether, this iPSC-based in vitro model provides a valuable platform to gain better understandings of ALS pathophysiology and can be used for future exploration of potential therapeutic drugs.