Nanoparticles for use for treating a neuronal disorder
Inventors
Meyre, Marie-Edith • Pottier, Agnès • Levy, Laurent
Assignees
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Publication Number
US-11717684-B2
Publication Date
2023-08-08
Expiration Date
Abstract
The present invention relates to the medical field, in particular to the treatment of neurological disorders. More specifically the present invention relates to a nanoparticle or nanoparticles' aggregate for use in prevention or treatment of a neurological disease or at least one symptom thereof in a subject when the nanoparticle or nanoparticles' aggregate is exposed to an electric field, wherein the nanoparticle's or nanoparticles' aggregate's material is selected from a conductor material, a semiconductor material, an insulator material with a dielectric constant εijk equal to or above 200, and an insulator material with a dielectric constant εijk equal to or below 100. It further relates to compositions and kits comprising such nanoparticles and/or nanoparticles' aggregates as well as to uses thereof.
Core Innovation
The invention is a method for normalizing impaired synchronization of oscillations within and/or between neuronal networks within and/or between distinct regions of the brain in a patient in need thereof. The method comprises administering a composition comprising nanoparticles and/or nanoparticles aggregates and a pharmaceutically acceptable support, followed by exposing the subject to an electric field.
The nanoparticle or nanoparticle aggregate material is selected from either a conductor material or an intrinsic semiconductor material. The conductor material is a metal having a standard reduction potential E0 above 0.2 selected from Pd, Pt and Au, and the intrinsic semiconductor material has a band gap Eg below 3.0 eV selected from an element from group IVA, a mixed composition of elements from groups III and V, or a mixed composition of elements from groups II and VI of the Mendeleev’s periodic table.
The concept is directed to neuronal oscillations and neuronal networks, where the impaired synchronization is normalized to improve neuronal network communication. The disclosed use context includes neurological disorders addressed by exposure to an electric field such as deep brain stimulation (DBS), transcranial electric stimulation (TES), and transcranial magnetic stimulation (TMS).
Claims Coverage
The disclosed claim set is centered on a single independent method claim with dependent claims that refine nanoparticle identity, nanoparticle surface/coating charge, the patient population, and a composition requirement involving at least two distinct nanoparticle or aggregate materials. The core claim defines administering a nanoparticle-containing composition and exposing the subject to an electric field together with specific nanoparticle material sets for conductors and intrinsic semiconductors.
Normalizing impaired synchronization of oscillations in neuronal networks
A method for normalizing impaired synchronization of oscillations within and/or between neuronal networks within and/or between distinct regions of the brain in a patient in need thereof.
Nanoparticle composition with pharmaceutically acceptable support and constrained material selection
Administering a composition to the subject, the composition comprising nanoparticles and/or nanoparticles aggregates and a pharmaceutically acceptable support, wherein the nanoparticle or nanoparticles aggregate material is selected from a conductor material of a metal having a standard reduction potential E0 above 0.2 selected from Pd, Pt and Au, and an intrinsic semiconductor material with a band gap Eg below 3.0 eV selected from an element from group IVA, a mixed composition of elements from groups III and V, and a mixed composition of elements from groups II and VI of the Mendeleev’s periodic table.
Exposing the subject to an electric field
Exposing the subject to an electric field as part of the method.
Gold nanoparticles with defined biocompatible coating/charge variants
The method wherein the composition comprises gold nanoparticles coated with a biocompatible hydrophilic agent having a neutral surface charge or coated with a biocompatible agent having a negative surface charge.
Silicon nanoparticles with defined biocompatible coating/charge variants
The method wherein the composition comprises silicon nanoparticles coated with a biocompatible hydrophilic agent having a neutral surface charge or coated with a biocompatible agent having a negative surface charge.
Targeting specified neurological diseases and symptoms
The method wherein the patient suffers from a neurological disease, or at least one of its symptoms, selected from Parkinson disease, Alzheimer disease, autism spectrum disorder, a depression disorder, schizophrenia, dementia, or bipolar disorder.
At least two distinct nanoparticle or aggregate materials drawn from the conductor and semiconductor sets
The method wherein the composition includes at least two distinct nanoparticles or nanoparticle aggregates made of different materials including a conductor metal with a standard reduction potential E0 above 0.2 selected from Pd, Pt and Au, and an intrinsic semiconductor material with band gap Eg below 3.0 eV selected from an element from group IVA, a mixed composition of elements from groups III and V, and a mixed composition of elements from groups II and VI of the Mendeleev’s periodic table.
Overall, the claim coverage focuses on normalizing impaired synchronization of oscillations in neuronal networks by administering a nanoparticle or nanoparticle aggregate composition with pharmaceutically acceptable support where the materials are restricted to specific conductor metals or intrinsic semiconductor materials, and exposing the subject to an electric field. Dependent claims further specify coating and charge variants for gold and silicon nanoparticles, narrow the patient population to enumerated neurological diseases or symptoms, and require at least two distinct nanoparticle or aggregate materials when composition-level material diversity is used.
Stated Advantages
Improved neuronal network communication by normalizing neuronal oscillation synchrony or coherence.
Improved focality, spatial resolution, and depth penetration.
Reduced stimulation thresholds and toxicity.
Documented Applications
Preventing or treating neurological disorders by using nanoparticles and/or nanoparticle aggregates together with exposure to an electric field, including deep brain stimulation (DBS), transcranial electric stimulation (TES), and transcranial magnetic stimulation (TMS).
Method application modeling electrically-stimulated network functional effects using in vitro microelectrode arrays (MEA) with Parkinson-like and Alzheimer-like models using MPP+ and amyloid beta 1-42 (Abeta 1-42), assessed using multiparametric spike, burst, and synchronicity metrics including an Effect Score.
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