Peripheral Neuropathy and Our Drug

What is Peripheral Neuropathy?

The human nervous system has two main parts: the central nervous system (the spinal cord and brain) and the peripheral nervous system consisting of peripheral sensory nerves made up of sensory neurons, the longest cell type in our body. Sensory neurons pick up signals from sensory receptors at their dendrites and release them at their axon terminals to transfer them to the next neuron or the spinal cord and, ultimately, the brain.  Normally, all of this occurs virtually instantaneously.

In peripheral neuropathy (PN), the peripheral sensory nerves become damaged as a result of injury or disease and cannot make these transfers efficiently or at all.  (In diabetic peripheral neuropathy (DPN), for instance, the degeneration of nerve terminals occurs specifically in the limbs and is caused by a high blood glucose level that disrupts the neurotransmission). This nerve damage leads to a disturbance in sensory function and symptoms ranging from tingling or persistent pain to a muted or complete loss of feeling.

WinSanTor’s Solution

WinSanTor has discovered a cellular pathway (a homeostatic mechanism) in sensory neurons which normally stimulates nerve growth and proper functioning through the formation of new neural connections between damaged and undamaged neurons, i.e., plasticity. DPN, for example, “turns off” this pathway.  After the WinSanTor team discovered this pathway, they introduced an antagonist (the drug) to essentially “turn the pathway back on” in order to successfully treat PN.  (Please keep in mind that although this drug is believed to work for multiple indications of PN, the mechanism below is specific to treating DPN).

The Drug’s Mechanism

  1. The antagonist (drug) binds to a G-protein coupled receptor (GCPR) located on the cell membrane of a sensory neuron
Within minutes, the next few things happen:
  1. Intracellular calcium levels slowly increase for up to an hour
  2. There is an increase in the activity of enzymes (such as AMP-activated protein kinase (AMPK)) that activate transcription factors (like peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha))
  3. The newly activated transcription factors ultimately produce proteins that drive mitochondrial function. The transcription factors achieve this by aiding in the transcription of DNA into RNA, which are subsequently translated into proteins.

Roughly 30-60 minutes later: 

  1. The new proteins increase the activity and/or number of mitochondria which leads to an increase of available ATP (energy).
  2. The ATP molecules provide the energy necessary for nerve growth!
  1. The nerve growth can be seen in two ways: the extension in axon length and the formation of new axons in a process known as branching (shown below).