Masitinib for the treatment of Alzheimer's disease

2021 ◽  
Vol 11 (4) ◽  
pp. 263-276
Author(s):  
Miren Ettcheto ◽  
Amanda Cano ◽  
Elena Sanchez-López ◽  
Ester Verdaguer ◽  
Jaume Folch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kinase Inhibitor ◽  
Phase Iii ◽  
Protein Signaling ◽  
Positive Effects ◽  
Activity Inhibition ◽  
Pharmacological Targets ◽  
Preclinical And Clinical Studies ◽  
Phase Iii Studies

The actual standard treatment for mild-to-moderately severe Alzheimer's disease only attacks its symptoms. Masitinib is a potent and selective phenylaminothiazole-type tyrosine kinase inhibitor which is currently in Phase III studies for the treatment of Alzheimer's disease (AD) with the aim of modifying its evolution and with multiple pharmacological targets such as inhibition of mast cells activity, inhibition of microglia activation, modulation of Aβ and Tau protein signaling pathway and prevention of synaptic damage. Here, we review the preclinical and clinical studies that investigated the administration of masitinib treatment in monotherapy in AD. All research studies revealed positive effects concerning the cognitive functions in AD and generally with good safety and tolerability.

scholarly journals Genetic underpinnings in Alzheimer’s disease – a review

2017 ◽  
Vol 29 (1) ◽  
pp. 21-38 ◽  
Author(s):  
Ahmed A. Moustafa ◽  
Mubashir Hassan ◽  
Doaa H. Hewedi ◽  
Iman Hewedi ◽  
Julia K. Garami ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Genetic Research ◽  
Twin Studies ◽  
Pedigree Analysis ◽  
Protein Signaling ◽  
Genetic Components ◽  
Genome Wide ◽  
Pharmacological Targets

AbstractIn this review, we discuss the genetic etiologies of Alzheimer’s disease (AD). Furthermore, we review genetic links to protein signaling pathways as novel pharmacological targets to treat AD. Moreover, we also discuss the clumps of AD-m ediated genes according to their single nucleotide polymorphism mutations. Rigorous data mining approaches justified the significant role of genes in AD prevalence. Pedigree analysis and twin studies suggest that genetic components are part of the etiology, rather than only being risk factors for AD. The first autosomal dominant mutation in the amyloid precursor protein (APP) gene was described in 1991. Later, AD was also associated with mutated early-onset (presenilin 1/2,PSEN1/2andAPP) and late-onset (apolipoprotein E,ApoE) genes. Genome-wide association and linkage analysis studies with identified multiple genomic areas have implications for the treatment of AD. We conclude this review with future directions and clinical implications of genetic research in AD.

Safety of rivastigmine in Alzheimer's disease: Pooled results from phase III studies

2000 ◽  
Vol 21 ◽  
pp. 170
Author(s):  
Steven G. Potkin ◽  
John C. Messina ◽  
Stephen Graham
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase Iii ◽  
Phase Iii Studies

scholarly journals Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Francesco Panza ◽  
Vincenzo Solfrizzi ◽  
Davide Seripa ◽  
Bruno P. Imbimbo ◽  
Madia Lozupone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase Ii ◽  
Animal Studies ◽  
Passive Immunization ◽  
Phase Iii ◽  
Positive Effects ◽  
Amyloid Accumulation ◽  
Phase Iii Trials ◽  
Tau Aggregation

The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD) with drugs targetingβ-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid.

O1-06-04: Efficacy of solanezumab in patients with mild or moderate Alzheimer's disease: Pooled analyses findings from two phase III studies

2013 ◽  
Vol 9 ◽  
pp. P139-P139 ◽  
Author(s):  
Christopher Carlson ◽  
Karen Sundell ◽  
Wahiba Estergard ◽  
Joel Raskin ◽  
Hong Liu-Seifert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Studies

scholarly journals Effects of Acupuncture on Alzheimer’s Disease in Animal-Based Research

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Sunjung Park ◽  
Jun-Hwan Lee ◽  
Eun Jin Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Studies ◽  
Sufficient Evidence ◽  
Therapeutic Effects ◽  
Functional Deficits ◽  
Positive Effects ◽  
Therapeutic Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles, and severe functional deficits in the brain. The pathogenesis and treatment of AD remain topics of investigation and significant global socioeconomic issues. The effect of complementary medicine has been investigated in managing AD. Acupuncture, a form of therapy practiced for more than 3000 years, has shown positive effects on several neurological disorders including AD. Animal studies have evaluated the specific utility and neuropathological mechanisms addressed by acupoint manipulation; however, no study has summarized the relationships among different acupoints and their therapeutic effects in the context of AD. Therefore, we reviewed the effects of acupuncture at different acupoints in animal models of AD. In general, acupuncture produced therapeutic benefits in rodent models of AD. Studies demonstrate the utility of GV20 as a valuable acupoint for electroacupuncture and manual acupuncture. GV20 stimulation suppresses Aβ generation, improves glucose metabolism, and attenuates neuropathological features in various disease models. However, a lack of sufficient evidence in preclinical and clinical studies makes these results controversial. Additional studies are required to confirm the exact utility of specific acupoints in clinically managing AD.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Old Drugs with New Tricks; Paradigm in Drug Development Pipeline for Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Tanay Dalvi ◽  
Bhaskar Dewangan ◽  
Rudradip Das ◽  
Jyoti Rani ◽  
Suchita Dattatray Shinde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Molecular Targets ◽  
Drug Repurposing ◽  
Phase Iii ◽  
Complex Nature ◽  
New Drug ◽  
Development Pipeline ◽  
Old Drugs

: The most common reason behind dementia is Alzheimer’s disease (AD) and it is predicted to be the third lifethreatening disease apart from stroke and cancer for the geriatric population. Till now only four drugs are available in the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidences of molecular targets are the major hurdles for developing new drug to treat AD. The the rate of attrition of many advanced drugs at clinical stages, makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repursing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) which has 27 candidates, and around half of the number are drugs which have already been approved for other indications. Although in the past the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we are reviewing the clinical candidates for AD with emphasis on their development history including molecular targets and the relevance of the target for AD.

scholarly journals Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Sirui Guo ◽  
Jiahong Wang ◽  
Huarong Xu ◽  
Weiwei Rong ◽  
Cheng Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Protein Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Single Target ◽  
Biological Methods ◽  
Cognition Impairment ◽  
First Time

Alzheimer’s disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aβ25-35 and D-gal-induced AD rats and Aβ25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aβ25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

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