Clinical and Market Analysis of NanoBEO: A Public-Worth, Innovative Therapy for Behavioral and Psychological Symptoms of Dementia (BPSD)—Emerging Evidence and Its Implications for a Health Technology Assessment (HTA) and Decision-Making in National Health Systems DOI Creative Commons
Damiana Scuteri,

Daniele Pierobon,

M. Pagliaro

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1253 - 1253

Published: Sept. 27, 2024

According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms dementia (BPSD), also known as neuropsychiatric (NPSs). In particular, agitation is one the most difficult disorders treat. States represent a very serious problem they make these subjects dangerous for themselves others worsen advances. To date, there are no specific solutions treating agitation. The only authorized drug risperidone (as well brexpiprazole, approved FDA on 11 May 2023), which can be used longer than 6-12 weeks because it increases risk death-owing cardiocerebrovascular accidents-by 1.6-1.7 times.

Language: Английский

Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer’s disease DOI
Madia Lozupone, Vittorio Dibello, Rodolfo Sardone

et al.

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: 19(6), P. 639 - 647

Published: April 29, 2024

In the last decade, efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aβ clearance was supposed to primarily contribute AD development progression, disease-modifying therapies with anti-Aβ monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab donanemab) are ongoing in randomized clinical trials (RCTs) contrasting results.

Language: Английский

Citations

7
The higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect DOI Creative Commons
Daniel Andrews, Simon Ducharme, Howard Chertkow

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 1, 2025

Abstract INTRODUCTION The phase 3 trial CLARITY AD found lecanemab slowed cognitive decline by 27%. However, subgroup analyses indicated a significant 31% sex difference in the effect and suggested no or limited effectiveness females. We used simulations constrained design to determine whether that reflects pre‐existing Alzheimer's disease progression was random event. METHODS Simulations were generated using linear mixed models of fit data from Disease Neuroimaging Initiative participants satisfying inclusion criteria. RESULTS statistically non‐significant 7.9% smaller rate our cohort's males versus females does not explain AD's lecanemab's effect. A ≥ occurred randomly only 12 10,000 (0.0012 probability). DISCUSSION probably random. Lecanemab is likely less effective than males, but we cannot conclude drug ineffective Highlights more clinically Forest plots should report subgroup‐specific effects well‐powered subgroups. Trial based on real enable investigation effects. efficacy could be linked its action mechanism.

Language: Английский

Citations

0
New insight into the role of altered brain cholesterol metabolism in the pathogenesis of AD: a unifying cholesterol hypothesis and new therapeutic approach for AD DOI Creative Commons
Xiaobo Yang, Kai Yao, Mengqi Zhang

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111321 - 111321

Published: March 1, 2025

The dysregulation of cholesterol metabolism homeostasis has been universally suggested in the aeotiology Alzheimer's disease (AD). Initially, studies indicate that alteration serum level might contribute to AD. However, because blood-brain barrier impedes entry plasma cholesterol, brain cells are not directly influenced by cholesterol. Furthermore, mounting evidences suggest a link between and Interestingly, Amyloid-β proteins (Aβ) can markedly inhibit cellular biosynthesis lower content cultured cells. And Aβ overproduction/overload induces significant decrease familial AD (FAD) animals. Importantly, mutations or polymorphisms genes related transportation, such as ApoE4, ATP binding cassette (ABC) transporters, low-density lipoprotein receptor (LDLR) family Niemann-Pick C 1 2 (NPC1/2), obviously lead decreased transport, resulting loss, which could be tightly associated with pathological impairments. Additionally, accumulating data show there reduction and/or disorder trafficking variety sporadic (SAD) animals patients. Collectively, compelling FAD SAD share one common overlapping neurochemical mechanism: neuronal/cellular deficiency. Therefore, accumulated strongly support novel hypothesis deficiency contributes onset progression This review highlights pivotal role pathogenesis offers valuable insights for future development treatment.

Language: Английский

Citations

0
Efficacy of therapeutic intervention with NanoBEO to manage agitation and pain in patients suffering from severe dementia: a pilot clinical trial DOI Creative Commons
Damiana Scuteri,

M. Pagliaro,

Isabel Mantia

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 1, 2024

Background An estimated 57.4 million people live with dementia worldwide, the social burden of disease steadily growing. Despite approval lecanemab and ongoing trials, there is still a lack effective safe treatments for behavioral psychological symptoms (BPSD), which affect 99% patients. Agitation one most disabling BPSD, cross-sectional prevalence ≥50% in nursing homes, refers to help-seeking behavior response various sources discomfort, among pain crucial component. Methods This pilot phase BRAINAID (NCT04321889) trial aimed assess effectiveness patented nanotechnological device NanoBEO older (≥65 years) severe dementia. randomized placebo-controlled trial, quadruple masking that involved all operators participants, followed SPIRIT CONSORT statements. A total 29 patients completed trial. The were randomly allocated 1:1 ratio or placebo group, corresponding product was applied on both arms once daily 4 weeks, 4-week follow-up period. primary endpoint efficacy against agitation. secondary endpoints agitation at pain. Any adverse events reported, biochemical analyses performed. Results intervention reduced frequency (28%) level disruptiveness agitated behaviors. effect statistically significant after 2 weeks treatment. behaviors lasted entire treatment No additional psychotropic drugs prescribed throughout study duration. results 1 week demonstrated had analgesic (45.46% improvement intensity). well tolerated. Discussion investigated therapy managing need rescue medications recorded, strengthening prolonged advanced-stage usefulness deprescription potentially harmful drugs. provided robust rationale application subsequent large-scale pivotal allow clinical translation product. Clinical Trial Registration: ClinicalTrials.gov , identifier NCT04321889.

Language: Английский

Citations

1
The higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect DOI Creative Commons
Daniel Andrews, Simon Ducharme, Howard Chertkow

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Abstract INTRODUCTION The Phase 3 trial CLARITY AD found that lecanemab slowed cognitive decline by a statistically significant 27% vs. placebo. However, the subgroup analysis indicated sex difference in effect, and recent work has implied either no or limited effectiveness females. To resolve this ambiguity, we used simulations constrained design to determine whether could be explained known differences Alzheimer’s progression, as an isolated random event. METHODS Simulations were generated using linear mixed models of fit data from ADNI participants who satisfied inclusion criteria. RESULTS nonsignificant 7.9% rate observed our selected does not explain trial’s 31% lecanemab’s effect. A ≥31% occurred randomly only 12 10,000 simulations, signifying probability 0.0012. DISCUSSION Our results are consistent with those AD. Lecanemab likely affects females males differently, but cannot conclude drug is ineffective

Language: Английский

Citations

0
Infection, Neuroinflammation and Interventions for Healthy Brain and Longevity DOI
Tamàs Fülöp, Charles Ramassamy, Guy Lacombe

et al.

Healthy ageing and longevity, Journal Year: 2024, Volume and Issue: unknown, P. 255 - 275

Published: Jan. 1, 2024

Language: Английский

Citations

0
Clinical and Market Analysis of NanoBEO: A Public-Worth, Innovative Therapy for Behavioral and Psychological Symptoms of Dementia (BPSD)—Emerging Evidence and Its Implications for a Health Technology Assessment (HTA) and Decision-Making in National Health Systems DOI Creative Commons
Damiana Scuteri,

Daniele Pierobon,

M. Pagliaro

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1253 - 1253

Published: Sept. 27, 2024

According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms dementia (BPSD), also known as neuropsychiatric (NPSs). In particular, agitation is one the most difficult disorders treat. States represent a very serious problem they make these subjects dangerous for themselves others worsen advances. To date, there are no specific solutions treating agitation. The only authorized drug risperidone (as well brexpiprazole, approved FDA on 11 May 2023), which can be used longer than 6-12 weeks because it increases risk death-owing cardiocerebrovascular accidents-by 1.6-1.7 times.

Language: Английский

Citations

0