Efficacy of Gene Therapy to Restore Cognition in Alzheimer’s Disease: A Systematic Review

Tedeschi, Desyrre V; Cunha, Anderson Ferreira da; Cominetti, Márcia Regina; Pedroso, Renata Valle

doi:10.2174/1566523221666210120091146

Cited by 3 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an emerging technology, gene therapy has promised numerous exciting possibilities: curing genetic ailments, , dissolving tumors, , treating neurodegenerative diseases, , increasing healthy longevity, , and even helping better equip astronauts for long-term survival on Mars. , AAV vectors represent one of the most prominent delivery technologies for gene therapy due to their minimal immunogenicity, tissue-selective serotypes, amenability to capsid modifications, and clinical successes. − In recent years, the FDA has approved three AAV gene therapies: Luxturna for Leber’s congenital amaurosis, Zolgensma for spinal muscular atrophy, and Hemgenix for hemophilia B . Yet these so-called miracle treatments represent some of the most expensive therapies in the world, carrying price tags of around $850,000, $2,100,000, and $3,500,000 respectively. − The titanic prices stem in large part from challenges involved in manufacturing recombinant AAVs. , As such, new manufacturing innovations are desperately needed so that gene therapy can fulfill its potential.…”

Section: Introductionmentioning

confidence: 99%

“…As an emerging technology, gene therapy has promised numerous exciting possibilities: curing genetic ailments, 1 , 2 dissolving tumors, 2 , 3 treating neurodegenerative diseases, 4 , 5 increasing healthy longevity, 6 , 7 and even helping better equip astronauts for long-term survival on Mars. 8 , 9 AAV vectors represent one of the most prominent delivery technologies for gene therapy due to their minimal immunogenicity, tissue-selective serotypes, amenability to capsid modifications, and clinical successes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

2023

View full text Add to dashboard Cite

Gene therapy has demonstrated enormous potential for changing how we combat disease. By directly engineering the genetic composition of cells, it provides a broad range of options for improving human health. Adeno-associated viruses (AAVs) represent a leading gene therapy vector and are expected to address a wide range of conditions in the coming decade. Three AAV therapies have already been approved by the FDA to treat Leber’s congenital amaurosis, spinal muscular atrophy, and hemophilia B. Yet these therapies cost around $850,000, $2,100,000, and $3,500,000, respectively. Such prices limit the broad applicability of AAV gene therapy and make it inaccessible to most patients. Much of this problem arises from the high manufacturing costs of AAVs. At the same time, the field of synthetic biology has grown rapidly and has displayed a special aptitude for addressing biomanufacturing problems. Here, we discuss emerging efforts to apply synthetic biology design to decrease the price of AAV production, and we propose that such efforts could play a major role in making gene therapy much more widely accessible.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

2023

View full text Add to dashboard Cite

show abstract

“…Gene therapy has shown significant potential for the treatment of Alzheimer’s disease in preclinical trials [6]. However, the challenge of gene therapy is well-tolerated and effective delivery vectors.…”

Section: Introductionmentioning

confidence: 99%

PEG-PEI/siROCK2 inhibits Aβ42-induced microglial inflammation via NLRP3/caspase 1 pathway

et al. 2021

View full text Add to dashboard Cite

ObjectivesThere is an urgent need to develop therapeutic strategies to improve the treatment outcome of Alzheimer's disease. The treatment strategy of gene therapy mediated by nanocarrier systems brings new hope for the treatment of Alzheimer's disease. ROCK2 is involved in various pathological processes of Alzheimer's disease and may be a potential target for the treatment of Alzheimer's disease. Our previous study indicated that PEG-PEI/siROCK2 [polyethyleneglycol-polyethyleneimine deliver ROCK2-siRNA, (PPSR)] prevented Aβ 42 -induced neurotoxicity and showed a promising prospect for the treatment of Alzheimer's disease. However, whether PPSR has an effect on the microglial inflammation in Alzheimer's disease is still unclear.Materials and methods 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cytotoxicity of PEG-PEI and PPSR in primary microglial cells. Real-time PCR and western blotting were used to assess the expression of ROCK2 and nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase 1 pathway in primary microglial cells. ELISA assay was used to measure the effect of PPSR on attenuating the lipopolysaccharide (LPS) + Aβ-induced increase in IL-1β.Results PEG-PEI concentration less than 20 μg/ml and the N/P (molar ratio of PEG-PEI amino/siRNA phosphate) ratio of PPSR less than 50 showed no significant cytotoxicity in primary microglia cells. PPSR could effectively inhibit the expression of ROCK2 in primary microglial cells. A further study revealed that PPSR attenuates the LPS+Aβ-induced increase in IL-1β without affecting cell viability. In addition, we found that PPSR suppressed the Aβ-induced NLRP3/caspase 1 pathway in primary microglial cells. ConclusionPPSR inhibits Aβ 42 -induced microglial inflammation via NLRP3/caspase 1 pathway. NeuroReport

show abstract

Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges

Safiri,

Ghaffari Jolfayi,

Fazlollahi

et al. 2024

Front. Med.

View full text Add to dashboard Cite

BackgroundAlzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired reasoning. It is the leading cause of dementia in older adults, marked by the pathological accumulation of amyloid-beta plaques and neurofibrillary tangles. These pathological changes lead to widespread neuronal damage, significantly impacting daily functioning and quality of life.ObjectiveThis comprehensive review aims to explore various aspects of Alzheimer's disease, including its epidemiology, risk factors, clinical presentation, diagnostic advancements, management strategies, caregiving challenges, and emerging therapeutic interventions.MethodsA systematic literature review was conducted across multiple electronic databases, including PubMed, MEDLINE, Cochrane Library, and Scopus, from their inception to May 2024. The search strategy incorporated a combination of keywords and Medical Subject Headings (MeSH) terms such as “Alzheimer's disease,” “epidemiology,” “risk factors,” “symptoms,” “diagnosis,” “management,” “caregiving,” “treatment,” and “novel therapies.” Boolean operators (AND, OR) were used to refine the search, ensuring a comprehensive analysis of the existing literature on Alzheimer's disease.ResultsAD is significantly influenced by genetic predispositions, such as the apolipoprotein E (APOE) ε4 allele, along with modifiable environmental factors like diet, physical activity, and cognitive engagement. Diagnostic approaches have evolved with advances in neuroimaging techniques (MRI, PET), and biomarker analysis, allowing for earlier detection and intervention. The National Institute on Aging and the Alzheimer's Association have updated diagnostic criteria to include biomarker data, enhancing early diagnosis.ConclusionThe management of AD includes pharmacological treatments, such as cholinesterase inhibitors and NMDA receptor antagonists, which provide symptomatic relief but do not slow disease progression. Emerging therapies, including amyloid-beta and tau-targeting treatments, gene therapy, and immunotherapy, offer potential for disease modification. The critical role of caregivers is underscored, as they face considerable emotional, physical, and financial burdens. Support programs, communication strategies, and educational interventions are essential for improving caregiving outcomes. While significant advancements have been made in understanding and managing AD, ongoing research is necessary to identify new therapeutic targets and enhance diagnostic and treatment strategies. A holistic approach, integrating clinical, genetic, and environmental factors, is essential for addressing the multifaceted challenges of Alzheimer's disease and improving outcomes for both patients and caregivers.

show abstract

Efficacy of Gene Therapy to Restore Cognition in Alzheimer’s Disease: A Systematic Review

Cited by 3 publications

References 55 publications

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies

PEG-PEI/siROCK2 inhibits Aβ42-induced microglial inflammation via NLRP3/caspase 1 pathway

Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges

Contact Info

Product

Resources

About