New ALS drug Radicava comes with new questions as well
It is the first new drug for amyotrophic lateral sclerosis in 22 years.
Clinical trials in neurodegenerative disorders are facing high futility rates and rising development costs. We aim to review and exemplify the value of group sequential trial designs (i.e. designs with one or more prospectively planned interim analyses) within the field of amyotrophic lateral sclerosis (ALS).
In conclusion, SCA3 patients had lower BMI than matched controls and BMI is a predictor of disease progression in SCA3. Nutritional intervention to promote weight gain could be a promising strategy to impede SCA3 progression.
Conclusions DM/Q was well tolerated and significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials.
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Stephen A. Goutman, Kevin S. Chen, Ximena Paez-Colasante, Eva L. Feldman Amyotrophic lateral sclerosis (ALS) is a progressive, noncurable neurodegenerative disorder of the upper and lower motor neurons causing weakness and death within a few years of symptom onset. About 10% of patients with ALS have a family history of the disease; however, ALS-associated genetic mutations are also found in sporadic cases. There are over 100 ALS-associated mutations, and importantly, several genetic mutations, including C9ORF72, SOD1, and TARDBP, have led...
Abstract Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining sporadic cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged>60 years, and those with a family history of ALS are more likely to develop the disease (1-3). No cure for ALS has yet been identified, and the lac...
A leader in IBM ’ s development of a speech-recognition system, she relied on her laptop to communicate after Lou Gehrig ’ s disease left her paralyzed.
This study identifies miRNAs that are altered in ALS that may serve as potentials biomarkers. PMID: 29458840 [PubMed - in process]
Mitochondrial stress response is essential for cell survival, and damaged mitochondria are a hallmark of neurodegenerative diseases. Thus, it is fundamental to understand how mitochondria relay information within the cell. Here, by investigating mitochondrial-endosomal contact sites we made the surprising observation that the small GTPase Rab5 translocates from early endosomes to mitochondria upon oxidative stress. This process is reversible and accompanied by an increase in Rab5-positive endosomes in contact with mitochondria. Interestingly, activation of Rab5 on mitochondria depends on the Rab5-GEF ALS2/Alsin, encoded by...
Dextromethorphan 20mg /quinidine 10mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based upon phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety and tolerability for PBA following stroke, dementia or traumatic brain injury (TBI). Objective. To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. Design. Open-label trial evaluating twice daily DM/Q over 90 days.