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Targeting microsomal triglyceride transfer protein and lipoprotein assembly to treat homozygous familial

Meghan T Walsh1,2, M Mahmood Hussain2,3,4,5

  • 1a School of Graduate Studies, Molecular and Cell Biology Program, State University of New York Downstate Medical Center , Brooklyn , NY , USA.

Critical Reviews in Clinical Laboratory Sciences
|October 4, 2016
PubMed

Insights

Homozygous familial hypercholesterolemia (HoFH) is a severe genetic condition causing extremely high cholesterol. Lomitapide, an MTP inhibitor, effectively lowers LDL cholesterol in HoFH patients unresponsive to other treatments.

Area of Science:

  • Biochemistry
  • Genetics
  • Pharmacology

Background:

  • Homozygous familial hypercholesterolemia (HoFH) is a severe genetic disorder characterized by extremely high levels of plasma low-density lipoprotein cholesterol (LDL-C).
  • This condition significantly increases the risk of premature atherosclerosis, coronary heart disease, and early mortality.
  • Standard lipid-lowering therapies are often ineffective in HoFH patients, necessitating alternative treatments.

Purpose of the Study:

  • To elucidate the mechanisms of lipoprotein assembly and the role of microsomal triglyceride transfer protein (MTP) in this process.
  • To review the clinical and molecular basis of HoFH.
  • To summarize pre-clinical and clinical data on lomitapide and other MTP inhibitors for HoFH treatment.

Main Methods:

  • Review of scientific literature on lipoprotein assembly, MTP function, and HoFH.
  • Analysis of pre-clinical studies and clinical trials involving MTP inhibitors, particularly lomitapide.
  • Discussion of ongoing research and novel therapeutic strategies for HoFH.

Main Results:

  • Lomitapide inhibits MTP, reducing lipoprotein assembly and secretion.
  • Lomitapide has demonstrated the ability to lower plasma cholesterol levels by over 50% in HoFH patients.
  • MTP inhibitors represent a promising therapeutic avenue for HoFH.

Conclusions:

  • HoFH requires specialized treatment due to the inefficacy of conventional therapies.
  • Lomitapide offers a significant therapeutic option by targeting MTP, a key protein in lipoprotein assembly.
  • Further research into MTP inhibitors and other novel approaches is crucial for improving HoFH management.

Keywords:
Low density lipoproteinapolipoprotein Bcholesterolchylomicronshomozygous familial hypercholesterolemiahyperlipidemialomitapide

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