Effect of deoxyribonuclease I treatment for dementia in end-stage Alzheimer’s disease: a case report

Abstract

BackgroundAlzheimer's disease is the most common cause of dementia and is characterized by a progressive loss of brain tissue leading to amyloid-β accumulation and severe decline in cognitive function. The cause of Alzheimer’s disease is poorly understood, and available treatments are limited in their efficacy, particularly for patients with more severe symptoms.Case presentationWe report the case of a 77-year-old Caucasian man with severe dementia and behavioral disturbance secondary to Alzheimer’s disease treated with memantine who began adjunct treatment with deoxyribonuclease I. Prior to initiation of deoxyribonuclease I treatment, our patient appeared to be in a stuporous state, with a Mini-Mental State Examination score of 3 and a Functional Assessment Staging Test score of 7. After obtaining informed consent from family members, we started administration of 120 mg of deoxyribonuclease I per day (1500 KU/mg) for treatment of severe cognitive impairment.ConclusionsOur patient began to demonstrate rapid, considerable improvement in cognitive function 2 days following initiation of deoxyribonuclease I treatment. After 2 months of continued treatment, Mini-Mental State Examination and Functional Assessment Staging Test scores were 18 and 4, respectively.

Influence of the Aqueous Environment on Protein Structure—A Plausible Hypothesis Concerning the Mechanism of Amyloidogenesis

“…The topic of amyloidogenesis has been the subject of many scientific endeavors and a great variety of papers have been published, approaching the problem from all possible angles: diagnostics [63][64][65][66], therapeutic [67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] and structural/molecular [82][83][84][85]. Our publication does not, however, discuss amyloidogenesis as such, but rather the molecular processes which lead to the formation of fibrillary aggregates commonly referred to as amyloids.…”

Bacterial DNA promotes Tau aggregation

“…Further studies need to be done to investigate the molecular mechanism by which DNA from some species of bacteria produce effect while others do not alter tau aggregation.The findings obtained in the present work indicate that DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood brain and intestinal barriers as important sources of microbial DNA in the brain; indeed, altered gut permeability and disrupted BBB could precede AD development 64 . Moreover, we have recently described a clinical case showing improvement of cognition in an AD patient following therapy with deoxyribonuclease I enzyme, that cleaves cell-free DNA 65,66 .…”

Deoxyribonucleases and Their Applications in Biomedicine

“…Treatment with DNase I might eventually be helpful in neurodegenerative diseases, for example in patients with dementia in the end-stage of Alzheimer's disease [126]. Of course, further and larger interventional studies are required in order to evaluate the role of ecDNA in the neurodegenerative pathologies.…”