How Our Approach Works

The TB16-8 proprietary lead compound that will address this problem is a dual TRPV4 and TRPA1 ion channel inhibitor, thus it will prevent excess calcium influx into skin-innervating nerve fibers when the small molecule binds to the TRPV4 and TRPA1 channels.

Importantly, we are proposing to deliver our lead compound topically to the patients’ skin.

We intend to have the patient prepare before chemotherapy by applying our compound topically to skin to inhibit TRPV4 and TRPA1 in a preventative manner, thus accomplishing the key goal of neuroprotection by preventing toxic calcium overload of the pain-sensing sensory nerve cells and their nerve endings in the skin.

Our proposed to-skin topical treatment is continued as chemotherapy is initiated. TB16-8 topical treatment is then carried on throughout chemotherapy, thus maximizing a patient’s odds to end the chemotherapy on schedule by minimizing pain and irritation, securing:

  • Maximum anti-cancer effectiveness, thus increased survival
  • Minimum neurotoxicity
  • Subsequent minimum peripheral painful polyneuropathy (CIPN), caused by nerve-damaging chemotherapy.

Why it Works

chemo nerve damage
Sensory nerve cells that innervate skin have TRP ion channels as ionic receptors to respond to external cues such as hot, cold, touch and pain.

Treatment with several chemotherapeutic agents, such as taxol and related taxane compounds, sensitize these ion channels to open their gate and allow influx of calcium into the sensory neuron. Excess calcium ions entering the cells inappropriately enhance toxicity of the drugs and lead to further damage, which makes the peripheral nerve endings in the skin hypersensitive.

Two particularly important TRP ion channel receptors in this scenario are TRPV4 and TRPA1, both known to be involved in pain, inflammation, and as irritant receptors.

Both known to be critically involved in preclinical models of chemotherapy-induced painful peripheral polyneuropathy. Each of these channels allowing too much calcium into the nerve cell damages the cell and makes the peripheral nerve ending more sensitive.

In addition, other non-nerve cells in the skin can possibly contribute to injury and sensitization, also via calcium overload by inappropriate activation of TRPV4 and TRPA1.

iching and inflammation CIPN
With ongoing chemotherapy, sensitized TRPV4 and TRPA1 continue to function in excess mode, especially in response to normal stimulation, such as wearing socks or shoes, tight pants, or thermal stimulation.

This aggravates the problem of excessive calcium influx and calcium overload of the peripheral neuron. The sensory nerve cells cannot regenerate by cell division, and they have the arduous task of maintaining a peripheral process that is 105-times longer than the diameter of the nerve cell, where the critical machinery for proper sensation is located at the interface to the skin.


Atopic Dermatitis Treatment

Atopic dermatitis has a significant impact on population health with approximately 10% of US residents suffering from it. The disease can also powerfully affect children, even young children, interfering with their development and causing grave damage on their families.

Treatment options for atopic dermatitis have recently come up which are typically systemic and immunomodulatory, some of the newer treatments with precise molecular targeting. Patients with more severe disease will benefit from add-on topical treatment. Patients with milder disease are preferentially treated with a non-systemic approach to avoid regular systemic drug use.

In this new, hopeful landscape of atopic dermatitis, we are confident that TB16-8 as a topical will fulfill its enormous potential to become a component of a topical-plus-systemic approach for severe disease, and a unique asset in topical-only therapy for milder disease.

TRPV4 and TRPA1 Atopic Dermatitis