Modified Antisense Oligonucleotides for Tau RNA Suppression
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Solution Overview
Problem
Current management for Alzheimer's disease is limited to symptom relief, and there is a need for methods to address the underlying cause of neurodegeneration driven by hyperphosphorylated Tau protein accumulation and aggregation, which contribute to cognitive decline and neuronal damage.
Innovation Solution
Administering a therapeutically effective amount of a modified oligonucleotide, such as ISIS 814907, to reduce Tau RNA and/or Tau protein levels in human subjects, targeting intracellular and extracellular Tau aggregates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current management methods for Alzheimer's disease are used, then symptom relief is provided, but the underlying cause of neurodegeneration driven by Tau protein accumulation is not addressed
Solution Approach 1:
The patent extracts and removes the harmful Tau protein aggregates from the system using antisense oligonucleotides that bind to Tau mRNA, preventing protein synthesis and promoting degradation of existing Tau aggregates, thereby addressing the root cause rather than just symptoms
Solution Approach 2:
The patent introduces antisense oligonucleotides as intermediary molecules that mediate between the genetic material (mRNA) and the harmful protein product (Tau), blocking the translation process and facilitating the removal of toxic aggregates without directly interacting with the aggregates themselves
2Duration of action of stationary object
If modified oligonucleotides are administered to reduce Tau protein levels, then neurodegeneration is slowed, but the complexity of the treatment increases
Solution Approach 1:
The antisense oligonucleotides are designed to self-complement and form stable complexes with Tau mRNA, enabling the treatment to work through its own inherent molecular recognition properties without requiring complex external control systems or multiple administered components
Solution Approach 2:
The patent modifies the chemical parameters of the oligonucleotides (such as sugar modifications, phosphorothioate backbones) to enhance stability and binding affinity, achieving prolonged duration of action through molecular design rather than complex dosing regimens or delivery systems
Data Source
AI summary
Provided herein are methods of administering ISIS 814907 for ameliorating Alzheimer's disease, reducing Tau RNA, or reducing Tau protein in a human subject in need thereof. In certain embodiments, the Alzheimer's disease is mild Alzheimer's disease, Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, and/or Alzheimer's Disease Dementia (e.g., Mild Alzheimer's Disease Dementia). In certain instances, methods are useful for ameliorating at least one symptom or hallmark of a disease or disorder associated with Tau protein. In certain instances, the disease or disorder associated with Tau protein is a neurodegenerative disease or disorder. In certain instances, the disease or disorder associated with Tau protein is Alzheimer's disease or Fronto-temporal Dementia (FTD). In certain embodiments, the Alzheimer's disease is mild Alzheimer's disease, Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, and/or Alzheimer's Disease Dementia (e.g., Mild Alzheimer's Disease Dementia). In certain instances, the disease or disorder associated with Tau protein is a tauopathy. In certain instances, the disease or disorder associated with Tau protein is Frontotemporal Dementia with Parkinsonism-17 (FTDP-17), Progressive Supranuclear Palsy (PSP), Chronic Traumatic Encephalopathy (CTE), Corticobasal Ganglionic Degeneration (CBD), Pick Disease, Argyrophilic Grain Disease (AGD), Globular Glial Tauopathies, Epilepsy, and/or Dravet's Syndrome. Such symptoms or hallmarks include loss of memory, cognitive decline, loss of ability to understand or express speech, abnormal behavior, loss of and impaired motor function, or increase in the number and/or volume of neurofibrillary inclusions.