Reducing cellular cholesterol

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Reducing cellular cholesterol
Reducing cellular cholesterol  Small molecules
and methods to use to promote cholesterol efflux
from cells  
Inventor Fred Maxfield, PhD
Chairman, Department of Biochemistry Professor of
Biochemistry Vladimir Horowitz and Wanda
Toscanini Horowitz Distinguished Professor of
Neuroscience
Leader in the study of intracellular lipid and
protein trafficking Expert in the design and
execution of cell-based screening assays.
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Reducing cellular cholesterol
Markets
Dyslipidemia 25B NPC and other lipid
storage disorders 500M Drug-induced
phospholipidosis 13B
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Reducing cellular cholesterol

• Build-up of phospho-lipids can be caused by
• Genetic diseases, like Niemann-Pick C
• Drug treatment (e.g. statins cause
  phospolipidosis)
• CV disease atherosclerosis
• Kidney disease

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Assay and screening

• Automated microscopy assay based on imaging of
  filipin fluorescence for estimating cholesterol
  accumulation in lysosomal storage organelles.
• Primary screen of 14,956 compounds identified 14
  hits
• Secondary library of 3962 compounds identified 7
  compounds with greater efficacy and lower
  toxicity than the original hits.
• These compounds are effective at concentrations
  of 123 nM to 3 mM in reducing cholesterol
  accumulation

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• Developmental status
• Cell-based assay means ability to enter cells not
  in question
• Identification of hits targets underway
• Once have targets in hand, collaboration in place
  to conduct SAR and perform med chem
• Intellectual Property
• PCT Application pending claiming patentable
  chemical space around hits
• Availability
• Exclusive licenses available outside field of
  Niemann-Pick