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 relates to pharmaceutical compositions and methods for the treatment of neuromuscular, neurodegenerative, developmental, autoimmune, and metabolic diseases by inducing endogenous expression of brain derived neurotrophic factor (BDNF) through administration of 2,4-dinitrophenol (DNP) or its pharmaceutically acceptable forms. It provides effective dose regimens where DNP, used either alone or in combination with other therapies, elevates BDNF levels in systemic organs, including brain and muscle, in a safe and controlled dose range to confer neuroprotection and mitigate disease progression.

The problem addressed is the need for improved methods to induce BDNF expression, especially since direct administration of BDNF is challenged by the blood brain barrier and current approaches fail to adequately increase endogenous BDNF expression without toxicity. Many serious diseases—including Huntington's Disease, Optic Neuritis, Duchenne Muscular Dystrophy, Multiple Sclerosis, Rett Syndrome, Alzheimer's Disease, and others—are characterized by decreased or insufficient BDNF levels, muscle wasting, or neurodegeneration.

The core innovation is the discovery that chronic administration of DNP within a defined, non-toxic dose range (typically about 0.01 mg/kg to less than 10 mg/kg body weight, often specified as 0.01–5 mg/kg) induces a non-linear, dose-dependent rise in endogenous BDNF levels, providing lasting protective effects in animal models of multiple diseases. The invention claims immediate, controlled, and sustained release formulations of DNP as pharmaceutical compositions for treating these conditions by safely stimulating endogenous BDNF, leading to therapeutic benefits such as attenuation or remission of disease symptoms.

Claims Coverage

There are two independent claims in the patent, each covering inventive features related to DNP compositions for specific disease treatments.

The independent claims define compositions of DNP within a controlled dose range and specify release formulations for the targeted treatment of Huntington's Disease, Optic Neuritis, or Duchenne Muscular Dystrophy, distinguishing the invention by the specified dosing and formulation.

Stated Advantages

Documented Applications