Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial

Abstract

Rasagiline did not alter disease progression compared with controls over 12 months of treatment. Muscle Nerve, 2017.

On the Clinical Pharmacology of Reactive Oxygen Species

“…Efforts to prove an additional disease-modifying effect in this disease (NCT00256204) yielded ambiguous results, which caused the US Food and Drug Administration to refuse the corresponding application for an approved extension. Although rasagiline did seem to show indications of such a neuroprotective effect in ALS when added to the standard treatment riluzole (Ludolph et al, 2018), another trial found no effect on disease progression after 1 year of treatment (Statland et al, 2019). A phase IV clinical study investigating rasagiline for neuroprotection in retinal detachment (NCT02068625), suggested by data obtained with a mouse model (Eigeldinger-Berthou et al, 2012), was prematurely terminated on 31 December 2018 because of persistent recruitment difficulties.…”

Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients

“…The optimal way to determine engagement in studies that target brain energy metabolism and mitochondrial function is unclear. Blood‐based biomarkers can directly assess effects on metabolism or mitochondria in peripheral tissue 28‐30 but positive results do not guarantee concurrent central nervous system effects. Cerebrospinal fluid (CSF) changes could perhaps reassure in this respect, but CSF procurement may complicate participant recruitment, we lack validated CSF biomarkers of metabolism or mitochondrial function, and CSF is not itself brain tissue.…”

“…Blood-based biomarkers can directly assess effects on metabolism or mitochondria in peripheral tissue [28][29][30] Compared to the lower OAA dose, the higher OAA dose benefited the FDG PET SUVR across multiple regions. Other AD intervention studies also used FDG PET to assess brain energy metabolism engagement.…”

Teaching An Old Drug New Tricks: Repositioning Strategies for Spinal Muscular atrophy

“…Recently, rasalgiline underwent Phase II clinical trials in ALS patients, either alone or in combination with riluzole, with the latter demonstrating moderate success, which is thought to be due to rasalgiline's neuroprotective role through promoting mitochondrial stability (ClinicalTrials.Gov ID: NCT01786603; NCT01879241; NCT01232738) [44][45][46]. Indeed, increased MOA-B activity could contribute to mitochondrial dysfunction and neurodegeneration via accumulation of its aldehyde and reactive oxygen species by-products [47][48][49][50].…”