Feeling heat, cold and touch is a prerequisite for experiencing and interpreting the world around us and the ability is directly decisive for whether we survive or not. Exactly how these sensory expressions are translated into signals that the brain can interpret has long been unknown, but thanks to the American researchers David Julius and Ardem Patapoutian Today we have a certain understanding of how it works.
Got answers using chili peppers
Through the use of capsaicin, which is the chemical in chili peppers that causes the sensation of heat, the TRPV1 receptor was discovered in the late 1990s. The discovery was a major breakthrough and led to the identification of more receptors in the body and the addition of more pieces to the emotional puzzle. A few years later, we now have an understanding of how different temperature and mechanical stimuli are converted into signals that allow us to perceive and adapt to our environment. For this work, the David Julius and Ardem Patapoutian with the 2021 Nobel Prize in Physiology or Medicine.
Taking a new approach to TRPV1
Since the initial discoveries, researchers around the world have continued to work to further understand the function of the receptors and find out if they can be used in the treatment of various disease conditions. One of them is Dorte X. Gram, who is the founder and CEO of the Malmö-based development company Pila Pharma.
Primarily, research has previously investigated whether there is a possibility of developing a new form of painkiller via TRPV1, which could be an alternative to ibuprofen, paracetamol and opioids for chronic pain. Gram believes that TRPV1 may also have a role to play in type 2 diabetes, a thesis that has been validated by other drug developers who have shown that TRPV1 inhibitors affect both insulin secretion and insulin sensitivity.
Preparing for Phase II
To further confirm the thesis, Pila Pharma is now preparing a phase II study with the TRPV1-inhibiting drug candidate. XEN-D0501The goal of XEN-D0501 is to help the body regulate insulin levels, thereby providing patients with type 2 diabetes with better glucose tolerance. Read more about the latest news in the development here.
BioStock has contacted Gram to hear how she views the discoveries that form the basis for Pila Pharma's development have now been recognized with a Nobel Prize.
Your own research has revolved a lot around TRPV1. How does it feel that the discovery behind your guiding principle is now being awarded the Nobel Prize?
– This is absolutely fantastic. When I first read the headline, I didn't think it was Julius who received the prize, but then when I read more closely and realized that it was, among other things, the discoveries around TRPV1 that received the prize, I was overjoyed.
– It was Julius's group that developed the knockout model to show the effect of specific TRPV1 in pain and temperature. There are many possibilities to regulate sensory nerves, but TRPV1 is believed to be 'the gatekeeper' – if you have control over it, you have control over the nerve. This was only known when Julius had data from his knockout model.
– I have referred a lot to Julius's work during my own studies on TRPV1 and have also used the knockout mice he created in my research. If Julius had not made his discoveries, I would not have been able to do what I do today. At the same time, I believe that TRPV1 plays a bigger role than just pain and heat and see it as one of my goals to build on his discoveries and ensure that they can lead to something that can make life better for people.
What impact could this have on your project?
– After Julius's discoveries, many large companies have worked with various TRPV1 antagonists. Here, Amgen was far ahead with a candidate that, however, turned out to be difficult to dissolve and associated with severe side effects. When they published their results, TRPV1 in the field went from being a "threat" to being a "not".
– We are quite unique in that we have developed a substance that partly seems to work, but which has also been shown to be safe. We are also the only ones exploring the role that TRPV1 may have in diabetes. With the discoveries being recognized in the Nobel context, our target will receive clear validation and I expect in the long term that TRPV1 can go from “not” to “threat” again. That would make it easier for the company to gain greater acceptance for the target that we are working on.
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