First drug delivery method developed for mitochondrial diseases

What do Huntington’s disease, Lou Gehrig’s disease (familial amyotrophic lateral sclerosis; the disease the physicist Stephen Hawking is suffering from) and Alzheimer’s disease have in common? The answer is mitochondria; these diseases are now called mitochondrial diseases.

These incurable degenerative neurological or neuromuscular diseases, together with apoptosis (programmed cell death) and aging, are understood to occur largely at mitochondria sites. What then are mitochondria? Mitochondria (plural of mitochondrion) are part (organelle) of every cell in the body that contains genetic material. Mitochondria are responsible for processing oxygen thus converting foodstuff we eat into energy in the form of ATP for essential cellular functions; hence mitochondria are called “the powerhouse” of cells. Mitochondria are the only other organelle than nucleus that contains DNA.
Nuclear DNA has two copies per cell (except for sperm and egg), and each copy is inherited from the father and the mother. However, mitochondria contain their own DNA (ca. 1 percent of the total DNA), typically 5-10 copies, all inherited from the mother!

Mitochondrial medicine is an important newly developing medical subspecialty dealing with the mitochondrial diseases. However, development of therapeutic agents in this area has been extremely slow, at least in part, due to the lack of an appropriate means of delivering a drug selectively to mitochondria. Now this dire situation may change for the better. Professor Sung-Kee Chung of Department of Chemistry and his coworkers in the Bioorganic and Medicinal Chemistry Lab recently reported their progress in developing organelle selective drug delivery vectors in Angewandte Chemie, a premier chemical research journal. (Angewandte Chemie Int. Ed. 2007, 46, 5880)

In this paper Dr. Chung and his team describe the design and synthesis of the first molecular transporters that show high intracellular selectivity toward mitochondria. Human tissues and organs, especially the central nervous system including the brain, are tightly guarded by various security barriers. Any effective therapeutic agent must penetrate into these security blankets in order to have the desired curative effects. Thus, for the treatment of the neurological and neuromuscular mitochondrial diseases a drug should overcome the blood brain barrier and selectively target mitochondria. The newly developed drug transporters which are based on the sorbitol scaffold, a sugar-like molecule have shown to be capable of achieving these two goals.

“In the following phase of research we will try to actually demonstrate, in collaboration with many biologists and doctors, the efficacy of this technology by delivering therapeutic agents and genes to mitochondrial sites of diseased neural cells.” Dr. Chung said.

Professor Sung-Kee Chung
Department of Chemistry
Email: skchung@postech.ac.kr
Phone: +82-54-279-2103