Methods and compositions for diagnosis and management of neurodegerative diseases
Inventors
Patel, Niketa A. • Cai, Jianfeng
Assignees
Office of General Counsel of VA • University of South Florida St Petersburg
Publication Number
US-11214835-B1
Publication Date
2022-01-04
Expiration Date
2038-06-06
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Abstract
Described herein are assays, methods, and devices for diagnosing/prognosing Alzheimer's disease (AD) and/or a neurodegenerative disease in a subject. The assays, methods, and/or devices described herein can be configured to detect GAS5 long-coding RNAs and/or expression thereof in a sample from a subject.
Core Innovation
The invention as described therein provides assays, methods, and devices for diagnosing and prognosing Alzheimer's disease (AD) and/or a neurodegenerative disease in a subject by detecting GAS5 long non-coding RNAs (IncRNAs) and/or expression thereof in a sample from the subject. It also describes compounds capable of binding GAS5 IncRNA to modulate its amount and/or activity, with pharmaceutical formulations and methods of treatment using these compounds.
The problem being addressed is that Alzheimer's disease is a neurodegenerative disease associated with age, leading to cognitive decline and neuronal death, with no current medication able to slow its progression. Existing FDA-approved drugs only manage symptoms and have adverse side effects. There is a need for improved diagnostic, prognostic, preventative, and therapeutic options for AD and other neurodegenerative diseases.
Recent insights reveal that long non-coding RNAs participate in essential biological networks affecting gene regulation, but their involvement in AD etiology and pathology is unknown or poorly characterized. The invention identifies GAS5 IncRNA as a biomarker whose altered expression precedes disease development and can indicate early-stage AD or neurodegenerative disease. The assays employ capture molecules configured to specifically bind GAS5 RNA or corresponding cDNA to detect and quantify its presence in tissues, cells, bodily fluids, or exosomes.
Claims Coverage
The patent includes one independent method claim focused on administering a therapeutically effective amount of specified compounds for treatment, optionally with capture molecule-based detection steps for GAS5 RNA.
Method of treating Alzheimer’s disease, diabetes, or both by administering specific compounds
Administering a therapeutically effective amount of a compound having a structure of formula 1 and derivatives thereof, including specific sub-forms as defined by Formulas 3-4, 6-19, capable of binding a GAS5 long non-coding RNA to treat Alzheimer's disease, diabetes, or both.
Binding of GAS5 long non-coding RNA with sequence identity to SEQ ID NO: 1
Use of compounds capable of binding GAS5 long non-coding RNA with 90%-100% sequence identity to SEQ ID NO: 1, thereby modulating GAS5 RNA activity or levels for treatment.
Use of various administration routes for therapeutic compounds
Administering the compounds via multiple routes including oral, rectal, intraocular, inhaled, intranasal, topical, vaginal, parenteral, subcutaneous, intramuscular, intravenous, or intradermal.
Method including detection of GAS5 biomarker using capture molecules
Prior to or concurrent with treatment, contacting a sample from the subject with capture molecules configured to specifically bind GAS5 (gas5/SNHG2), detecting specific binding using various nucleic acid detection techniques such as PCR, qPCR, arrays, in situ hybridization, and others.
Capture molecules with sequences highly identical to SEQ ID NOs.: 2-3 for specific GAS5 detection
The capture molecules used have sequences 95%-100% identical to SEQ ID NOs.: 2-3 enabling specific and sensitive detection of GAS5 RNA.
Method applicable to subjects of different ages or diabetic status
The method is applicable to subjects greater or less than 45 years of age and to those having or suspected of having diabetes, demonstrating broad clinical applicability.
The claims cover methods of treating Alzheimer's disease and/or diabetes using compounds that bind to GAS5 long non-coding RNA, administered by various routes, with diagnostic methods employing specific capture molecules that detect GAS5 expression as a biomarker in subjects of various ages and diabetic statuses.
Stated Advantages
Provides earlier, improved, and more accurate diagnosis and prognosis of Alzheimer's disease and other neurodegenerative diseases by detecting altered expression of GAS5 IncRNA.
Offers potential therapeutic compounds that modulate GAS5 IncRNA levels or activity, addressing underlying disease mechanisms rather than only symptoms.
Enables noninvasive monitoring of treatment efficacy through detecting GAS5 levels in body fluids, tissues, and cells.
Provides pharmaceutical formulations and administration routes that facilitate effective delivery of GAS5 binding compounds, including routes that bypass the blood-brain barrier.
Documented Applications
Diagnosis and prognosis of Alzheimer's disease and other neurodegenerative diseases by detecting GAS5 IncRNA or corresponding cDNA in samples from subjects, including bodily fluids, tissues, cells, exosomes, and cell secretions.
Evaluating risk or early onset of neurodegenerative diseases prior to clinical symptoms by measuring GAS5 expression changes.
Monitoring response to treatment or management of Alzheimer's disease or other neurodegenerative diseases via changes in GAS5 levels.
Treatment of Alzheimer's disease, diabetes, or both by administering compounds capable of binding and modulating GAS5 IncRNA levels or activity.
Use of capture molecule-based assays including microarrays, PCR-based methods, in situ hybridization, and other nucleic acid detection techniques for detection of GAS5 as a biomarker.
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