Klotho And The Brain

  • 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 high levels of Klotho live 30% longer, are healthier and smarter
  • Kogenix co-founder Dr. Carmela Abraham and her team at Boston University School of Medicine discovered that Klotho levels are low in the aged brain
  • Klotho levels are also reduced in the CSF of Alzheimer’s and MS patients
  • Increased levels of circulating Klotho are associated with improved cognition in humans and mice
  • Klotho can be measured in blood, CSF, and urine, so the efficacy of treatment in increasing Klotho levels can be tested during clinical trials

Klotho Gene Therapy

Kogenix co-founders Dr. Miguel Chillon and Dr. Assumpcio Bosch and their teams at Vall d'Hebron Research Institute (VHRI), ICREA, and Universitat Autonoma Barcelona (UAB) used AAV vectors based Klotho gene therapy in the brain and studied cognition. Their yet unpublished findings support results of previous studies performed with Klotho overexpressing mice

Alzheimer’s Disease

  • Current drugs alleviate symptoms only in the early stage
  • Immunotherapy (clear amyloid from the brain) is finally showing some promise in one clinical trial while other trials continue to fail. It is too early to tell if this approach will work
  • The Kogenix approach: prevent neurodegeneration or slow it down
  • Neuroprotection versus removal of amyloid
  • One-time gene therapy

Initial AD validation

  • AD patients have reduced Klotho in their CSF
  • Klotho protects neurons from amyloid and glutamate toxicity
  • Klotho overexpression rescues behavioral deficits in an AD mouse model in the presence of amyloid deposits
  • Klotho gene therapy to the brain confirms previous findings of Klotho’s effects on cognition (not yet published)
  • Klotho gene therapy in AD mouse models – current pre-clinical work

Multiple Sclerosis

  • Many existing drugs are immunosuppressors/modulators
  • Little effect on disability progression
  • Aimed to reduce relapse rate/frequency
  • Significant side effects associated with highest efficacy drugs
  • Many are injectables, not oral
  • Kogenix’s approach – induce re-myelination
  • One-time gene therapy - neuroprotective and/or re-myelinating
  • Patients would regain function faster and to a larger extent
  • Use in conjunction with immunosuppressors

Initial MS validation

  • Klotho induces maturation of myelinating oligodendrocytes
  • Klotho deficient mice have abnormal myelin
  • Overexpression of Klotho induces re-myelination in an MS mouse model
  • Klotho gene therapy in MS mouse models – current pre-clinical work