NM101 Phase III Study of NE3107 in Alzheimer’s Disease: rationale, Design and Therapeutic Modulation of Neuroinflammation and Insulin Resistance

Reading, Christopher L.; Ahlem, Clarence N.; Murphy, Michael

doi:10.2217/nmt-2021-0022

Cited by 39 publications

(41 citation statements)

References 50 publications

(67 reference statements)

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“…The largest group of drugs tested in phase 3 of AD drug development consists of disease-modifying small molecules [ 105 ], which include substances modulating (i) metabolism and bioenergetics, e.g., metformin [ 354 , 355 ], semaglutide [ 356 ], and tricaprylin [ 357 , 358 ]; (ii) oxidative stress and blood flow in the brain, e.g., omega-3 polyunsaturated fatty acids [ 359 ] and ethyl eicosapentaenoate (icosapent ethyl) [ 360 ]; (iii) synaptic plasticity and neuroprotection, e.g., blarcamesine [ 361 , 362 ], atuzaginstat [ 363 ], AGB101 (levetiracetam) [ 364 , 365 ], and simufilam [ 366 ]; (iv) Aβ pathology, e.g., ALZ-801 (valiltramiprosate), an oral prodrug of homotaurine that blocks the formation of toxic Aβ oligomers [ 334 , 367 , 368 ]; (v) neuroinflammation, e.g., NE3107 [ 369 ] and curcumin [ 337 , 370 , 371 , 372 , 373 ]; and more. Disease-modifying drugs are also the monoclonal antibodies directed at Aβ; besides aducanumab [ 374 ] it is also gantenerumab [ 374 , 375 ], lecanemab [ 375 ], donanemab [ 376 ], and solanezumab [ 374 , 377 ], which have shown some efficiency and are tested in phase 3 clinical trials [ 317 ].…”

Section: Alzheimer’s Drugsmentioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

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Section: Alzheimer’s Drugsmentioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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“…A Phase III, double blind, randomized, placebo-controlled multicenter study of NE3107 in mild-to-moderate AD subjects is currently ongoing (NCT04669028). 74 …”

Section: Clinical Anti-inflammatory Ad Treatment Strategiesmentioning

confidence: 99%

Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease

Liu¹,

Wang²,

Sun³

et al. 2022

CIA

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Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), the precise pathophysiology of this deadly illness remains unclear and no effective remedies capable of inhibiting disease progression have been discovered. In addition to deposition of extracellular Aβ plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as the third core characteristic crucial in the pathogenesis of AD. More and more evidence from laboratory and clinical studies have suggested that anti-inflammatory treatments could defer or prevent the occurrence of AD. In this review, we will discuss multifaceted evidence of neuroinflammation presented in AD and the newly emerged anti-inflammatory targets both in pre-clinical and clinical AD.

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“…Under research. NCT04098666 [32] NE3107 (Phase 3) BioVie Inc Decreases inflammation and improves insulin function in human and preclinical models.…”

Section: Eli Lillymentioning

confidence: 99%

“…NE3107 is another drug which also reached the phase III (Clinicaltrials.gov: NCT04669028). Previous studies have shown that this drug has a dual therapeutic effect, presenting both neuroinflammatory and antidiabetic properties [32]. Hence, NE3107 has been reported to inhibit the in-flammatory ERK pathway and to the improve insulin signaling.…”

Section: Metabolism and Bioenergetics As Therapeutic Targetsmentioning

confidence: 99%

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Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

Olloquequi¹,

Ettcheto²,

Cano³

et al. 2022

Front. Biosci. (Landmark Ed)

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The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.

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NM101 Phase III Study of NE3107 in Alzheimer’s Disease: rationale, Design and Therapeutic Modulation of Neuroinflammation and Insulin Resistance

Cited by 39 publications

References 50 publications

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease

Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

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