Neurodegenerative Diseases: Current Research

Adamantanes for the Treatment of Neurodegenerative Diseases in the Era of the COVID-19 Pandemic

Kerstin Pilling¹ and Roger F Butterworth²

¹­Merz Pharmaceuticals GmbH, Frankfurt a.M. Germany
²Roger F Butterworth, 45143 Cabot Trail, Englishtown, Nova Scotia B0C 1H0, Canada

Abstract

Neurodegenerative diseases constitute co-morbidities along with diabetes, cardiovascular disease and obesity leading to worsening of clinical outcomes in patients infected with COVID-19. Adamantanes have established benefits in the treatment of neurodegenerative disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD) and multiple sclerosis (MS). Systematic reviews with meta-analysis confirm the efficacy of amantadine for the treatment of the motor signs of PD and for L-Dopa-induced dyskinesias. COVID-19 may result in worsening of the symptoms of PD and conversely, certain features of COVID-19 may aggravate tremor, gait disturbances, dyskinesias and the efficacy of L-Dopa. Antibody responses to coronaviruses have been observed in CSF samples of PD patients. Interestingly, amantadine is potentially effective for the treatment of COVID-19 per se via the down-regulation of host cell proteases and inhibition of protein E ion channel activity resulting in decreased viral replication. Three reports appeared of possible COVID-19 prophylaxis by long-term treatment with amantadine in patients with PD infected with SARS-CoV-2. In the case of AD, meta-analyses reveal the efficacy of memantine leading to its approval by US-FDA for treatment of moderate-to-severe forms of AD. Both AD and COVID-19 are functionally linked to amyloid and to activation of NMDA receptors. Indeed, both conditions derive clinical benefit from treatment with memantine or amantadine both of which are non-competitive NMDA receptor antagonists. A case of COVID-19 prophylaxis is described in a report of 7 patients with severe cognitive impairment treated for several months with memantine and subsequently exposed to SARS-CoV-2. None of the 7 treated patients developed symptoms of infectious disease. Amantadine is also effective for the treatment of fatigue in MS and for the cognitive and neurobehavioral complications of traumatic brain injury (TBI) where amantadine, rimantadine and memantine are employed.

Keywords:

adamantanes, neurodegenerative diseases, Parkinson’s disease, Alzheimer’s disease, fatigue in multiple sclerosis, traumatic brain injury, amantadine, rimantadine, memantine