Costly New Alzheimer Disease Medications on the Horizon—Financing Alternatives for Medicare

Fleming, William K.; Brown, Courtney; Shrank, William H.

doi:10.1001/jamahealthforum.2020.1148

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…2 Despite showing some promising efficacy in removing β-amyloid, only patients with mild stage and amyloid burden can be benefited from the expensive treatment (estimated to cost $56,000 per year). 3 To develop potential treatments in a timely and cost-effective manner, drug repurposing has shown good potential due to the reduced risk of drug toxicity of previously approved drugs. What is even more promising is to study combinatorial drug repositioning, which has demonstrated their potential for synergistically treating complicated diseases, including cancer, 4 diabetes, 5 metabolic syndrome, 6 and cardiovascular disease, 7 thanks to their ability to target multiple pathologies.…”

Section: Introductionmentioning

confidence: 99%

Synthesize heterogeneous biological knowledge via representation learning for Alzheimer’s disease drug repurposing

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Synthesize heterogeneous biological knowledge via representation learning for Alzheimer’s disease drug repurposing

et al. 2023

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“…These achievements support the concept that it is important to inhibit Aβ aggregation before the onset of AD symptoms. However, treatments with antibodies are very expensive [14] and are thus not accessible to most people.…”

Section: Introductionmentioning

confidence: 99%

Cultivation Factors That Affect Amyloid-β Aggregation Inhibitory Activity in Perilla frutescens var. crispa

Shimamori

Nambu

Kawamata

et al. 2023

Foods

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Alzheimer’s disease (AD) is thought to be caused by the deposition of amyloid-β (Aβ) in the brain. Aβ begins to aggregate approximately 20 years before the expression of its symptoms. Previously, we developed a microliter-scale high-throughput screening (MSHTS) system for inhibitors against Aβ aggregation using quantum dot nanoprobes. Using this system, we also found that plants in the Lamiaceae, particularly Perilla frutescens var. crispa, have high activity. The cultivation environment has the potential to enhance Aβ aggregation inhibitory activity in plants by changing their metabolism. Here, we report on cultivation factors that affected the activity of P. frutescens var. crispa cultivated in three fields under different cultivation conditions. The results revealed that the activity of P. frutescens var. crispa harvested just before flowering was highest. Interestingly, the activity of wind-shielded plants that were cultivated to prevent exposure to wind, was reduced to 1/5th of plants just before flowering. Furthermore, activity just before flowering increased following appropriate nitrogen fertilization and at least one week of drying from the day before harvest. In addition, we confirmed that the P. frutescens var. crispa leaf extracts suppressed Aβ-induced toxicity in nerve growth factor-differentiated PC12 cells. In this study, we demonstrated that flowering, wind, soil water content, and soil nitrogen content affected Aβ aggregation inhibitory activity, necessary to suppress Aβ neurotoxicity, in P. frutescens var. crispa extracts. This study provides practical cultivation methods for P. frutescens var. crispa with high Aβ aggregation inhibitory activity for the prevention of AD.

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“…The Aβ protein was chosen to demonstrate the validity of the proposed protocol as its aggregation leads to one of the most abundant neurodegenerative diseases, 51 Alzheimer's disease (AD), which presently lacks any definitive curable form of the administrable drug. 52 The absence of a specific therapeutic makes AD a life-threatening disease 53 with an economically challenging treatment procedure for the patients 54 and thus has been widely studied for decades now. It is broadly accepted that the genesis of AD has its root in the gradual accumulation of the proteolytic cleavage products of the Amyloid Precursor Protein (APP), Aβ peptides, and concomitant membrane damage by the aggregated construct (amyloid hypothesis).…”

Section: ■ Introductionmentioning

confidence: 99%

Scan-Find-Scan-Model: Discrete Site-Targeted Suppressor Design Strategy for Amyloid-β

Bhagavatula¹,

Sarkar

Santra

et al. 2022

ACS Chem. Neurosci.

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Alzheimer’s disease is undoubtedly the most well-studied neurodegenerative disease. Consequently, the amyloid-β (Aβ) protein ranks at the top in terms of getting attention from the scientific community for structural property-based characterization. Even after decades of extensive research, there is existing volatility in terms of understanding and hence the effective tackling procedures against the disease that arises due to the lack of knowledge of both specific target- and site-specific drugs. Here, we develop a multidimensional approach based on the characterization of the common static-dynamic-thermodynamic trait of the monomeric protein, which efficiently identifies a small target sequence that contains an inherent tendency to misfold and consequently aggregate. The robustness of the identification of the target sequence comes with an abundance of a priori knowledge about the length and sequence of the target and hence guides toward effective designing of the target-specific drug with a very low probability of bottleneck and failure. Based on the target sequence information, we further identified a specific mutant that showed the maximum potential to act as a destabilizer of the monomeric protein as well as enormous success as an aggregation suppressor. We eventually tested the drug efficacy by estimating the extent of modulation of binding affinity existing within the fibrillar form of the Aβ protein due to a single-point mutation and hence provided a proof of concept of the entire protocol.

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Costly New Alzheimer Disease Medications on the Horizon—Financing Alternatives for Medicare

Cited by 4 publications

References 8 publications

Synthesize heterogeneous biological knowledge via representation learning for Alzheimer’s disease drug repurposing

Synthesize heterogeneous biological knowledge via representation learning for Alzheimer’s disease drug repurposing

Cultivation Factors That Affect Amyloid-β Aggregation Inhibitory Activity in Perilla frutescens var. crispa

Scan-Find-Scan-Model: Discrete Site-Targeted Suppressor Design Strategy for Amyloid-β

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