Induced expression of brain derived neurotrophic factor (BDNF) for treatment of neuromuscular, neurodegenerative, autoimmune, developmental and/or metabolic diseases
Inventors
Alonso, Robert • Geisler, John Gerard
Assignees
Publication Number
US-11717497-B2
Publication Date
2023-08-08
Expiration Date
2036-01-21
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A method of treating a host of neuromuscular, neurodegenerative, developmental, autoimmune and metabolic diseases/disorders related to aging, such as traumatic injury, stroke, Huntington's disease, Epilepsy, Multiple Sclerosis (MS), Lupus, Type-1 and Type-2 diabetes, Maturity Onset Diabetes of the Young (MODY), myasthenia gravis (MG), rheumatoid arthritis (RA), Graves' disease, Guillain-Barré syndrome (GBS), metabolic syndrome, Muscular Dystrophy or Duchenne Muscular Dystrophy (DMD), severe burns, aging, Amyotrophic Lateral Sclerosis (ALS), Friedreich's Ataxia, Batten Disease, Alzheimer's disease, optic neuritis, Leber's hereditary optic neuropathy (LHON), autism, Rett syndrome, Batten Disease, Angelman's Syndrome, Leigh disease, Fragile-X Syndrome, depression, Parkinson's disease, mitochondrial diseases, developmental disorders, metabolic disease disorders and/or autoimmune disorders by inducing endogenous BDNF expression with DNP treatment to protect from neuromuscular dysfunction/disorders and/or neurodegeneration and/or muscle wasting. DNP was administered to mice daily over a range of doses, and subsequently BDNF expression in the brain showed a dose dependent and non-linear increase in expression.
Core Innovation
The invention provides methods and pharmaceutical compositions for treating neuromuscular, neurodegenerative, autoimmune, developmental, and/or metabolic diseases by inducing the expression of brain-derived neurotrophic factor (BDNF) through administration of 2,4-dinitrophenol (DNP) or its pharmaceutically acceptable salt, solvate, or hydrate. The induction of BDNF is achieved by administering DNP at an effective dose defined as being in the range of about 0.001 mg/kg to about 5 mg/kg of body weight, offering a safe and effective way to leverage BDNF's neuroprotective and myoprotective roles.
The invention addresses the problem that current approaches to increasing BDNF levels face significant obstacles, such as delivering BDNF across the blood-brain barrier and finding methods that are both effective and safe. The invention identifies that DNP can endogenously induce BDNF expression and that there exists a specific dose range which is effective and not harmful, nor too low to be ineffective. The effectiveness of DNP in inducing BDNF is dose-dependent but not linear, with a bell-shaped response curve.
Through chronic administration of DNP, BDNF levels are increased in the brain and muscle tissue, contributing to attenuation of disease progression or remission of symptoms in a range of diseases, including but not limited to Amyotrophic Lateral Sclerosis (ALS), Atypical Parkinsonism, and Autism Spectrum Disorders (ASD). The invention further encompasses pharmaceutical compositions and unit doses of DNP, methods of administering such compositions, and instructions for their use, covering a wide spectrum of diseases and modes of delivery.
Claims Coverage
There are three independent claims, each defining a method for treating specific diseases or disorders with 2,4-dinitrophenol (DNP) by dosage parameter or unit dose, and/or by means of administration or instruction.
Method of treating ALS, atypical parkinsonism, or ASD with DNP at specific weight-based dose range
A method comprising administering to a patient in need of treatment a pharmaceutical composition of 2,4-dinitrophenol (DNP), or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the effective dose of DNP is in the range of about 0.001 mg/kg of body weight to about 5 mg/kg of body weight, for a disease or disorder selected from Amyotrophic Lateral Sclerosis (ALS), Atypical Parkinsonism, and an Autism Spectrum Disorder (ASD).
Method of treating ALS, atypical parkinsonism, or ASD with DNP by unit dose
A method comprising administering to a patient in need of treatment a pharmaceutical composition of 2,4-dinitrophenol (DNP), or a pharmaceutically acceptable salt, solvate, or hydrate thereof, comprising a 2,4-dinitrophenol (DNP) unit dose, wherein the unit dose is in the range of about 0.1 mg to about 300 mg, for treating a disease or disorder selected from ALS, Atypical Parkinsonism, and ASD.
Method of treating ALS, atypical parkinsonism, or ASD with DNP by administration or instruction
A method of treating a disease or disorder selected from ALS, Atypical Parkinsonism, and ASD comprising: receiving a pharmaceutical composition of 2,4-dinitrophenol (DNP), or a pharmaceutically acceptable salt, solvate, or hydrate thereof, comprising an effective dose of DNP, or providing instructions to administer such a composition, wherein the effective dose of DNP is in the range of about 0.001 mg/kg of body weight to about 5 mg/kg of body weight.
The inventive features encompass methods of treating ALS, atypical parkinsonism, and autism spectrum disorders by administering DNP (or related salt/solvate/hydrate) in defined dose ranges based on body weight or as a specific unit dose, including methods involving direct administration or provision of instructions for such administration.
Stated Advantages
Induces endogenous expression of BDNF to provide neuroprotection and muscle protection in various diseases.
Utilizes a defined dose range of DNP that is effective in increasing BDNF while avoiding harm from excessive dosing or ineffectiveness from too low dosing.
Provides a means to treat diseases where increased BDNF expression leads to reversal, slowing, or prevention of disease progression and/or remission of symptoms.
Offers lasting elevation of BDNF levels after cessation of DNP administration.
Documented Applications
Treatment of Amyotrophic Lateral Sclerosis (ALS) by administering DNP at effective doses or unit doses.
Treatment of Atypical Parkinsonism, including progressive supranuclear palsy, dementia with Lewy bodies, multiple system atrophy, and corticobasal degeneration.
Treatment of Autism Spectrum Disorder (ASD), including Asperger's Syndrome, Pervasive Developmental Disorders (PDDs), Childhood Disintegrative Disorder (CDD), and Autistic disorder.
Interested in licensing this patent?