Henk de Wilde, chief operating officer and R&D Director, iQure Pharma discusses how better understanding of pain is helping researchers to develop novel therapeutics as non-opioid alternatives to manage neuropathic pain.
Key insights:
- Neuropathic pain develops from an injury or disease of the nervous system, most current treatments produce debilitating side effects.
- Treatment of a neuropathic pain patient needs to address multiple mechanisms to deliver a meaningful change in the pain perception of an individual patient.
- iQure is testing novel compounds that help to modulate glutamate, an excitatory neurotransmitter that forms a key step in the pain signaling process.
Chronic pain is one of the most common reasons people seek health care and the leading cause of disability in the world. One of the most severe forms of chronic pain—neuropathic pain—affects over 10 million adults in the United States and nearly 1 in 12 adults worldwide. The population prevalence of chronic neuropathic pain has been estimated to be 7% to 10%.
Neuropathic pain develops from an injury or disease of the nervous system. It can produce unrelenting jabbing or burning pain that doesn’t respond to current pain treatments for the majority of patients. In addition, current treatments are often associated with debilitating side effects, such as dizziness and somnolence. The pain itself, but also the side effects associated with current pain treatments, can impact all aspects of daily life, as well as sleep, and mental health.
Persistent chronic pain leaves patients slogging through life while they quietly harbour a pain that’s “24/7,” or feels like “a blow torch on their body” or “a nail pounded into the same location over and over again,” as reported by a number of patients captured in an FDA report on neuropathic pain titled “The Voice of the Patient.”
Identifying better neuropathic pain relief
Current treatments, including anti-seizure drugs and tricyclic antidepressants, are effective for some patients, but millions of other patients fail to respond, or respond insufficiently. At the same time, as many as 30% or more of patients stop taking their initial medication because of associated side effects. In fact, between 43-54% of all patients treated ultimately turn to opioids, even though opioid analgesics haven’t been particularly effective for neuropathic pain. All this unnecessarily contributes to the opioid crisis. According to the WHO, more than 70% of the half million drug-use deaths worldwide are related to opioids. A need for better methods of neuropathic pain relief is therefore critical.
The experience of neuropathic pain is the result of a complex combination of increased stimulation of peripheral neurons, a heightened sensitisation of such neurons, decrease in the threshold of those neurons to be stimulated, a decreased ability of neurons to return to a resting state, or a permanent change in the central modulation of the perception of the pain caused by these hypersensitised neurons. Each of these steps is managed through a combination of (subtype) receptors and channels, and each step is inextricably linked to another. In addition, the original cause of the neuropathic pain (e.g. chemotherapy, diabetes, genetic predisposition) may result in a different expression of the damage caused, resulting in altered perceptions of the pain.
Finally, inflammatory pain and neuropathic pain, previously considered distinctly different pain types, can be both a cause and a result of each other and therefore may co-exist in a single neuropathic patient. This understanding makes it clear that the treatment of a neuropathic pain patient needs to address multiple mechanisms to deliver a meaningful change in the pain perception of an individual patient.
Researching novel compounds to treat pain and epilepsy
By acknowledging the complexity of the pain response and understanding the role all different mechanisms play, researchers at iQure Pharma are working to deliver significant and lasting analgesia to patients. iQure is testing novel compounds that help to modulate glutamate, an excitatory neurotransmitter that forms a key step in the pain signaling process. Its overstimulation can lead to excitotoxicity—neurons becoming dysfunctional or dying due to an excessive release of glutamate. This excessive release of glutamate is implicated in both neuropathic pain and epilepsy.
Another solution to this complexity of pain biology, the primary reason for ineffective current available treatment, is a multi-targeting approach, offered by iQ-008, a rationally designed compound that works on sodium (Na+) and calcium (Ca2+) channels, and on the TRPV1/CB2 complex. As each pathway contributes in a different way to the development and maintenance of chronic pain, and depending on the underlying cause of the individual patient, the simultaneously blocking of each pathway can increase the number of patients responding, as well as improve the overall response within a patient.
In an often-cited report on “the global tragedy of needless pain,” noted global health lawyer and Georgetown University Law professor Allyn Taylor, J.D., LL.M, J.S.D., said: “for millions of people across the globe, excruciating pain is an inescapable reality of life.”
iQure Pharma’s goal is to provide different approaches that can provide better therapeutics for neuropathic pain, responding to the estimated 1 in 5 adults globally who suffer from pain, in addition to the 1 in 10 adults diagnosed with chronic pain each year.
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