Company Research

Legendary Pharmaceuticals has been established to develop pharmaceutical drugs and gene therapies which repair and reverse accumulating molecular damage to subcellular mitochondria, lysosomes, nuclei, and extracellular proteins in order to prevent and treat serious late-onset diseases commonly associated with aging.

[Click here for an Introduction to the Biology of Aging.]

New understandings in the sciences of Genetics, Genomics, Proteomics, Cell Biology and the Physiology of Aging are combining with new capabilities in the technologies of Combinatorial Chemistry, Computer Science, High Throughput Screening, and Rational Drug Design to permit the development of novel drugs and gene therapies specifically targeted at correcting the processes and repairing the damage which cause some of the most serious declines of aging.

Electron microscope Because age-related diseases progress by several parallel biochemical mechanisms, Legendary Pharmaceuticals is conducting several parallel tracks of proprietary research. The goal is development of an arsenal of several drugs and gene therapies which will work synergistically together for more complete repair.

Primary research tracks are directed at correcting gradual deterioration of:

  • Mitochondria in nondividing cells;
  • Lysosomes in nondividing cells of the brain, muscle, and heart.
  • Lamin A (progerin) components of cell nuclei.
  • Accumulations of damaged, crosslinked proteins outside of cells.
Mitochondria are subcellular organelles which oxidize fuels (sugars and fats) to produce chemical energy (ATP) for cellular processes. Over time, mutation damage accumulates in the mitochondrial DNA of a small percentage of cells. The results include gradual losses of cells in the brain, spinal cord, skeletal muscle, and heart muscle. Many symptoms of aging derive from these cell losses, including neurodegenerative diseases and loss of muscle mass.

Living cells also have repair systems, including lysosomes and proteasomes that break down damaged or unneeded proteins, lipids, and mitochondria. Over the decades, these important turnover functions become less effective. As a result, damaged substances and mutant mitochondria accumulate in the cells, which become less able to support the health of the body. These accumulations contribute to neurodegenerative diseases, heart disease, atherosclerosis, and macular degeneration.

Altered forms of the Lamin A protein accumulate in the nuclei of aging cells, altering the nuclear architecture. This interferes with proper functioning of mesenchymal lineage cells, contributing to many diseases of aging, including cardiovascular diseases.

Legendary Pharmaceuticals researchers are developing molecular interventions which restore the effectiveness of these subcellular energy, architectural, and garbage disposal systems. Cells composed of undamaged molecules, and containing better lysosomes, proteasomes, nuclei, and mitochondria, will function like younger cells, and support a younger-feeling, younger-functioning body.

In parallel, Legendary Pharmaceuticals is studying the age-related accumulation of damaged proteins outside of cells. Plaques of amyloid beta protein accumulate in the brain. They produce free radicals which may kill brain cells, causing senility and Alzheimer's disease. Other damage affects extracellular proteins throughout the body, such as collagen and elastin. Recycling of these proteins proceeds slowly, so damage accumulates; they are out of reach of proteasomes and lysomes. Over time, they are chemically altered by reactive chemicals and sugars, which form covalent adducts and crosslinks. Crosslinked and glycated extracellular proteins contribute to many pathologies of aging and diabetes, including atherosclerosis, heart disease, stiffness, kidney diseases, arthritis, and erectile dysfunction. We are studying several promising mechanisms for breaking these crosslinks, as well as drugs which quench reactive free-radicals before they can chemically damage the proteins.

[Click here for an Introduction to the Biochemistry of Glycation and Crosslinking.]

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