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

Mitochon Pharmaceuticals Inc

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 a method for treating neuromuscular, neurodegenerative, developmental, autoimmune, and metabolic diseases or disorders related to aging by inducing endogenous brain-derived neurotrophic factor (BDNF) expression through administration of 2,4-dinitrophenol (DNP). The induction of BDNF is achieved by administering DNP, or a pharmaceutically acceptable salt thereof, in effective dose ranges identified as 0.001 mg/kg to less than 10 mg/kg, to avoid doses that are either ineffective or potentially harmful. The method is applicable for reversing, slowing, or preventing disease progression or providing remission of symptoms by increasing BDNF systemically, including both in the brain and muscle tissues.

The problem being addressed is the current need for improved methods to induce endogenous expression of BDNF, particularly for treating a wide range of diseases where increased BDNF can provide neuroprotection, muscle protection, and address dysfunction across multiple organ systems. Existing challenges include delivering BDNF across the blood-brain barrier and achieving sufficient and sustained expression without adverse effects. The invention addresses this by identifying specific dose ranges and administration regimens for DNP that effectively induce BDNF, with demonstrated efficacy in preclinical models for diseases such as Huntington's disease, Rett syndrome, multiple sclerosis, epilepsy, Alzheimer's disease, Parkinson's disease, and Duchenne Muscular Dystrophy, among others.

Supporting studies demonstrate that DNP administration in mouse models leads to dose-dependent increases in BDNF expression, with an observed non-linear relationship where excessively high doses yield diminished effects. The invention claims that using DNP within the identified dose range can result in significant neuroprotection, muscle sparing, and attenuation of disease progression in various animal models, supporting the method as a potential therapeutic strategy for a multitude of debilitating and chronic diseases. The formulation may take the form of pharmaceutical compositions with specified unit doses and may be delivered by oral, intravenous, subcutaneous, topical, or transdermal routes, with potential for co-administration with other standard-of-care medications.

Claims Coverage

The patent contains three independent claims, each covering distinct inventive aspects regarding the use and administration of 2,4-dinitrophenol (DNP) for treating Huntington's Disease, Optic Neuritis, or Duchenne Muscular Dystrophy.

The inventive features of the patent are centered on the administration, receipt, and instruction for applying effective dose ranges of DNP to treat Huntington's Disease, Optic Neuritis, or Duchenne Muscular Dystrophy, aiming to attenuate progression or provide remission of symptoms.

Stated Advantages

Documented Applications