Neuropathic pain, also known as chronic pain, is rather resistant to current treatments. A new target, discovered by the universities of Montpellier and Strasbourg, seems to represent a breakthrough to avoid the "chronicization" of these pains.
The neuropathic pain, or neurogenic pain, is a particular form of chronic pain, where hypersensitivity to pain (hyperpathy, allodynia) and abnormal sensations (burning, tingling ...) predominate. It is linked to a dysfunction of the nervous system which can intervene at different levels (peripheral nerve, spinal cord or brain).
The problem is that conventional painkillers do not work for a pain that would affect almost 10% of the population (diabetes, shingles, MS, traumatic lesions ...). We have to resort to drugs psychotropic (antidepressants, anti-epileptics ...), but less than 50% of patients consider themselves to be really improved and the effect is slow to obtain (at least one month of treatment).
FLT3 and its key role in pain
A team of researchers from the Universities of Montpellier and Strasbourg have launched a research program on neuropathic pain that has led to the discovery of a receptor, FLT3, which seems to play a key role.
FLT3 is a tyrosine kinase and its receptor is expressed on the surface of blood stem cells and immune cells. In case of nerve injury, an influx of immune cells occurs at the site of the lesion and these cells secrete an inflammatory protein which, because of the lesion, can reach the FLT3 receptor on the nerve and bind with it. activate.
It is this FLT3 protein-receptor binding that activates a chemical cascade in the nervous system and leads to pain and its persistence: FLT3 intervenes in the foreground in the phenomenon of "chronicization" of pain.
BDT001, a promising molecule
The research team therefore looked for an inhibitor of FLT3 by an original approach. They perfectly defined the 3-dimensional structure of the FLT3 receiver and searched in a database of 3 million molecules, which one could best suit in terms of complementary structure, as a key in a lock. With this approach, they discovered a molecule that seems very promising (BDT001) since it seems to perfectly block FLT3 and thus the cascade that leads to neuropathic pain.
Tested in an experimental model in mice, the new BDT001 molecule allows in less than 3 hours a significant reduction in hyperalgesia and allodynia. This effect lasted 48 hours with a single dose. These results are published in Nature Communications.
A development in progress
Other FLT3 inhibitors have been tried in the treatment of certain types of leukemia, but their development has been stopped because of the numerous side effects. BDT001 seems more promising from this point of view and has far fewer interactions with other drugs.
The researchers created a start-up to ensure the early stages of clinical development and have an injectable form for the first studies in humans in 2010.