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Kennedy’s Disease Drugs in Development by Stages, Target

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johnandrew
Kennedy’s Disease Drugs in Development by Stages, Target

Introduction

Kennedy's Disease, also known as Spinal and Bulbar Muscular Atrophy (SBMA), is a rare genetic disorder that affects the spinal cord and motor neurons in the brainstem. It mainly affects men and causes progressive weakness and wasting of muscles, leading to difficulties in swallowing, speaking, and walking. There is currently no cure for Kennedy's Disease, but several drugs are in development that target different stages of the disease.


Stages of Kennedy's Disease and Targeted Drugs

  • Stage 1: Protein Misfolding and AggregationThe androgen receptor (AR) protein misfolds and forms toxic aggregates that damage motor neurons.
  • Targeted drugs: Androgen receptor modulators, heat shock protein (HSP) inducers, and protein degradation enhancers.
  • Stage 2: Transcriptional DysregulationThe toxic aggregates of AR protein disrupt gene expression and cause transcriptional dysregulation.
  • Targeted drugs: Histone deacetylase inhibitors, transcriptional activators, and RNA polymerase modulators.
  • Stage 3: Mitochondrial DysfunctionTranscriptional dysregulation leads to mitochondrial dysfunction and energy depletion in motor neurons.
  • Targeted drugs: Mitochondrial antioxidants, metabolic enhancers, and energy boosters.
  • Stage 4: Neuroinflammation and Glial ActivationMitochondrial dysfunction and motor neuron death trigger neuroinflammation and glial activation.
  • Targeted drugs: Anti-inflammatory agents, glial modulators, and microglial inhibitors.
  • Stage 5: Muscle AtrophyMotor neuron death and muscle denervation result in muscle atrophy and weakness.
  • Targeted drugs: Muscle growth factors, muscle stem cell activators, and myostatin inhibitors.

Current Drug Development Programs

  • Androgen Receptor ModulatorsEnobosarm (GTx-024): A selective androgen receptor modulator (SARM) that targets AR protein misfolding and aggregation.
  • EPI-506: A small molecule inhibitor that blocks AR protein expression and prevents transcriptional dysregulation.
  • Histone Deacetylase InhibitorsValproic acid (VPA): A mood stabilizer and anticonvulsant that also inhibits histone deacetylase (HDAC) enzymes and restores gene expression.
  • Vorinostat (SAHA): A FDA-approved drug for cutaneous T-cell lymphoma that also inhibits HDAC enzymes and promotes transcriptional activation.
  • Mitochondrial AntioxidantsCoenzyme Q10 (CoQ10): A natural antioxidant that protects mitochondria from oxidative stress and improves energy production.
  • Methylene blue (MB): A synthetic dye that crosses the blood-brain barrier and acts as a mitochondrial electron carrier and antioxidant.
  • Anti-Inflammatory AgentsIbudilast (MN-166): A nonselective phosphodiesterase inhibitor and macrophage migration inhibitory factor (MIF) inhibitor that reduces neuroinflammation and glial activation.
  • Masitinib (AB1010): A tyrosine kinase inhibitor that targets mast cells and microglia and reduces neuroinflammation and oxidative stress.
  • Muscle Growth FactorsSRK-015: A monoclonal antibody that blocks myostatin, a negative regulator of muscle growth, and promotes muscle hypertrophy and strength.


To know more information : https://www.globaldata.com/store/report/kennedys-disease-drugs-in-development-analysis/


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