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Disease-Modifying Treatments and Their Future in Alzheimer’s Disease Management

Blake Smith • Raymond L. Ownby

Published: March 13, 2024
DOI: 10.7759/cureus.56105
https://www.cureus.com/articles/231134-disease-modifying-treatments-and-their-future-in-alzheimers-disease-management#!/

Comprehensive new review on AD treatments

Nice Fig 1 by authors on Amyloid plaque formation & subsequent inflammation through oxidative damage.

“Neuroinflammation is a key component in the pathology of AD.”

“One hundred and eighty-seven unique treatment agents for AD are undergoing trials as of January 1, 2023 [7]. Disease modification was by far the most common classification of drug agents undergoing testing in these trials as 79% of the agents targeted disease modification [7]. Disease-modifying treatment (DMT) is a label given to therapeutic agents whose purpose is to change the biology or slow the progression of AD [7]. It is reassuring that the major area of focus for drug development regarding novel treatments for AD is DMTs, as aducanumab and lecanemab are the only DMTs readily available today. This narrative review aims to investigate DMTs that have recently received U.S. Food and Drug Administration (FDA) approval in addition to DMTs in phase three of development that have the potential for approval in the near future. Figure 3 and Table 1 illustrate the diversity in therapeutic target areas of these novel DMTs.“

Icosapent Ethyl among 3 DMTs targeting oxidative stress.

Oxidative Stress

Amyloid-ß plaques cause oxidative stress to nearby lipid-containing cell membranes, leading to inflammation [21]. A class of DMTs in phase 3 of trials focuses on reducing this oxidative stress. Hydralazine hydrochloride is one of these. Hydralazine hydrochloride is able to reduce lipid oxidative damage through its hydrazide functional group and possesses antioxidant properties [21]. Hydralazine hydrochloride can prevent some of this oxidative stress by scavenging and removing the harmful products of lipid oxygenation. Hydralazine hydrochloride prevents lipid modifications of amyloid-ß plaques like many hydrazides but is unique from other hydrazides in that it was shown to reduce amyloid-ß misfolding [21]. Although hydralazine was capable of reducing amyloid-ß misfolding, it was unable to reduce the aggregation of these misfolded proteins into their pathological plaques [21]. Another potential focus area for targeting oxidative stress in AD is through omega-3 fatty acids, or the purified form of one of these fatty acids, icosapent ethyl. Icosapent ethyl is a purified form of eicosapentaenoic acid and was previously confirmed to be cardioprotective [7]. The rationale for icosapent ethyl being a possible treatment option for AD is that eicosapentaenoic acid is capable of improving arterial and cerebrospinal blood flow [22]. An increase in cerebrospinal blood flow can improve the physiological functioning of the brain with various processes [22]. Icosapent ethyl and its effect on cerebrospinal blood flow may attenuate some of AD’s neurotoxic effects by improving the brain’s function in removing waste and toxins from the central nervous system (CNS).”

Waiting for BRAVE results.
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