Klogene Therapeutics, Inc. is developing novel treatments for neurodegenerative diseases. Its first target is Alzheimer’s disease (AD). The company’s drug development platform is based on small molecule compounds that enhance the expression of the Klotho gene.
This gene was discovered by Dr. Makoto Kuro-o and he named it after the goddess Clotho, Zeus’ daughter, who spins the thread of life. Klotho is a large protein produced in the kidney and brain, that acts as a circulating growth factor. Klotho-deficient mice show many signs of human aging including cognitive decline, synaptic loss, abnormal CNS myelin, osteoporosis, atherosclerosis and die prematurely. Mice with increased levels of Klotho live 30% longer, are healthier and smarter.
Dr. Carmela Abraham’s team at Boston University School of Medicine was the first to show in 2003 that Klotho levels are lower in the aged brain. Klotho levels are also decreased in the cerebral spinal fluid of AD and multiple sclerosis (MS) patients. In contrast, increased levels of Klotho are associated with improved cognition in humans and mice. Dr. Abraham suggested in 2005 that small molecules that cross the blood-brain-barrier and enhance Klotho expression have the potential to become novel therapeutics for age related and other neurodegenerative diseases. See list of Dr. Carmela Abraham’s relevant publications in the last decade on the “Science” page of this website.
Klogene Therapeutics’ strategy in treatment of AD is based on protection of neurons from damage caused by amyloid. This potential therapeutic approach, based on up-regulation of Klotho, may work in conjunction with other approaches such as clearing of the amyloid.
The Klotho enhancing small molecule compounds R&D was performed in a collaboration that started in 2007 between Boston University School of Medicine (BUSM) and the Laboratory of Drug Discovery in Neurodegeneration at Harvard Medical School affiliated Brigham and Women’s Hospital (BWH). Klogene’s initial drug discovery platform is based on an exclusive license of the BUSM/BWH intellectual property.
In the future, through partnerships and/or subsidiaries, the company may target additional diseases that can potentially be treated by Klotho-enhancing drugs. Research performed at a number of academic institutions points to potential of Klotho-enhancing strategies in treatment of MS, orphan de-myelinating diseases, chronic kidney disease, and certain cancers.
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