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Amylyx begins dosing in Phase II trial of AMX0035 for ALS

Amylyx Pharmaceuticals has begun dosing patients in the Phase II CENTAUR clinical trial of its therapeutic candidate, AMX0035, to treat those with amyotrophic lateral sclerosis (ALS).
Source: Drug Development Technology - Category: Pharmaceuticals Source Type: news

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AbstractBackgroundOn initiation of long-term non-invasive ventilation (NIV), intermittent upper airway obstruction has rarely been described as possibly treatment-induced. Inspiratory pressure effects and the use of an oronasal interface may promote obstructive events in some patients with neuromuscular disease (NMD) and amyotrophic lateral sclerosis (ALS) in particular.MethodsWe evaluated clinical data from 212 patients in whom NIV was initiated using an oronasal mask. Treatment-induced upper airway obstruction (TAO) was defined as an AHI>  5/h along with a relative increase of the AHI in the first treatment nig...
Source: Sleep and Breathing - Category: Respiratory Medicine Source Type: research
Mutations in CHCHD2 and CHCHD10 were recently reported in a broad spectrum of neurodegenerative diseases, e.g. Parkinson ’s disease, amyotrophic lateral sclerosis, frontotemporal dementia or mitochondrial myopathy (MM). The aim of the study was to evaluate the prevalence of CHCHD2 and CHCHD10 mutations in Italian MM patients without mitochondrial DNA mutations. The coding regions of CHCHD2 and CHCHD10 were sequenced in 62 MM patients. None of the patients showed CHCHD2 mutations, whereas one sporadic MM patient carried a homozygous Pro96Thr substitution in CHCHD10.
Source: Neurobiology of Aging - Category: Neuroscience Authors: Source Type: research
Abstract The evolutionarily conserved FOXO family of transcription factors has emerged as a significant arbiter of neural cell fate and function in mammals. From the neural stem cell (NSC) state through mature neurons under both physiological and pathological conditions, they have been found to modulate neural cell survival, stress responses, lineage commitment, and neuronal signaling. Lineage-specific FOXO knockout mice have provided an invaluable tool for the dissection of FOXO biology in the nervous system. Within the NSC compartments of the brain, FOXOs are required for the maintenance of NSC quiescence and fo...
Source: Current Topics in Developmental Biology - Category: Biology Authors: Tags: Curr Top Dev Biol Source Type: research
Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis, Published online: 14 February 2018; doi:10.1038/s41419-018-0288-4Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis
Source: Cell death and disease - Category: Internal Medicine Authors: Source Type: research
Discussion: Biomarker data show that ALS is associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. Muscle Nerve, 2018
Source: Muscle and Nerve - Category: Internal Medicine Authors: Tags: Clinical Research Article Source Type: research
Authors: Hikiami R, Yamakado H, Tatsumi S, Ayaki T, Hashi Y, Yamashita H, Sawamoto N, Tsuji T, Urushitani M, Takahashi R Abstract We herein report a 15-year-old girl who developed rapid progressive muscle weakness soon after the third injection of a bivalent human papilloma virus (HPV) vaccine. Although immunotherapies were performed for possible vaccine-related disorders, she died of respiratory failure 14 months after the onset of the disease. A genetic analysis identified a heterozygous p.P525L mutation of the fused in sarcoma (FUS) gene, and a histopathological analysis was also consistent with FUS-associated a...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Publication date: Available online 12 February 2018 Source:Neuroscience Author(s): HaoJie Hu, HuiQian Lin, WeiSong Duan, Can Cui, ZhongYao Li, YaKun Liu, Wan Wang, Di Wen, Ying Wang, ChunYan Li Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative disorder characterized by the progressive loss of upper and lower motor neurons. Currently, there is no effective drug for ALS. Recent studies in ALS model mice have shown that insulin-like growth factor-1 (IGF1) may be a promising therapeutic drug. We demonstrate that self-complementary adeno-associated virus serum type 9 encoding the human IGF1 (scAAV9-hIGF...
Source: Neuroscience - Category: Neuroscience Source Type: research
Date: Tuesday, 03 27, 2018; Speaker: Bryan Traynor MD, PhD, MMSc, NIA; Mary Kay Floeter, MD, PhD, NINDS; Building: Building 50; 1227; Videocast Event
Source: NIH Calendar of Events - Category: American Health Source Type: events
Discussion: Mean‐MUNIX and NI were more sensitive than clinical measures at detecting LMN loss in presymptomatic limbs from patients with slowly progressive ALS. Therefore, these electrophysiological biomarkers should be included in early study phases as meaningful outcome measures. Muscle Nerve, 2018
Source: Muscle and Nerve - Category: Internal Medicine Authors: Tags: Clinical Research Article Source Type: research
AbstractGlutamate-induced excitotoxicity is considered as one of the major pathophysiological factors of motoneuron death in amyotrophic lateral sclerosis and other motoneuron diseases. In order to expand our knowledge on mechanisms of glutamate-induced excitotoxicity, the present study proposes to determine the metabolic consequences of glutamate and astrocytes in primary enriched motoneuron culture. Using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we showed that the presence of astrocytes and glutamate profoundly modified the metabolic profile of motoneurons. Our study highlights for th...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
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