José Luis Quintanar Stephano, researcher and professor at the Autonomous University of Aguascalientes, and his team determined in clinical trials that leuprolide acetate has neuroregenerative activity, which allows partially restoring movement and sensation in patients with spinal cord injuries.
A group of 45 patients who received an injection of leuprolide acetate each month have experienced improvements in body movement, sphincter muscles control and partial recovery of sensation in their extremities.
The results showed that the recovery rate is variable, depending on several factors like injury’s magnitude, level and time elapsed since it was suffered. On average, it was recorded a 40 regeneration in the group of patients, and the effects are permanent.
“The overall project is neuroregeneration, i.e. regeneration of the nervous system. We know that the nervous system does not reproduce as such; however, it can be regenerated: regenerate the neuron itself, the nervous tissue itself. It does not regenerate appearing new neurons, but the cell, if is somewhat altered, wounded or damaged, can still recover. Therefore, it can also perform its function, which is important,” Quintanar Stephano said in interview with CONACYT News Agency.
The researcher has already applied for a patent registration for a second use for leuprolide acetate, as neuroregenerative in patients with spinal cord injury, in the Mexican Institute of Industrial Property (IMPI).
A Lucky Break
Quintanar Stephano explained that while working with his team on cultured neurons, they noted by chance that the gonadotropin-releasing hormone (GnRH) induced growth in nerve cells.
“Then we were testing substances that already existed in the market, or that had already shown to produce growth. So we needed a negative control, a control where this effect would not manifest. And in that trial, we found exactly the opposite, an excessive growth; and that obviously caught our attention.”
Quintanar Stephano said that from this discovery, they conducted numerous studies with cultured neurons, in order to evaluate different variables, such as proteins, contact points and projections. Then, once they concluded in-vitro studies and after obtaining positive results, he decided to start experimenting with animal models.
He explained that they sought a challenge where neurological area was compromised, where the lesion could be seen, and they chose spinal cord injury. The researchers created an animal model of spinal cord injury by inserting a small balloon in the spinal cord of rats, causing a lesion when it was inflated. Then they deflated and removed the balloon; and the rat can no longer move the hind legs and tail.
Posteriorly, they treat the animals with GnRH; and they found a remarkable phenomenon: the rats recovered very significantly; not only recovering movement, but also in sphincter muscles control.
Quintanar Stephano said that they faced a problem because the substance they were using was very expensive, because they had to import it, which hindered their experimentation. Thus, they decided to find a more powerful and efficient synthetic analogue compound; which would not degrade as quickly as GnRH and could be administered in a systemic way. They found this synthetic analogue; and when they studied it, they found that it produced an even more significant recovery than GnRH.
Once they found this more powerful and efficient compound, they searched if there was a commercial compound with the same molecular formula. They found in the market leuprolide acetate, which is used in the treatment of hormone-responsive cancer, among other treatments, but not as a treatment for neuroregeneration. These were great news because, being a drug that already existed in the market; leuprolide acetate already had extensive basic research.
They tested the drug in rats, and the results were also notable. Since it showed minor side effects, and it was simple to apply through injections, they were able to obtain the authorization of the bioethics council to start clinical trials.
They chose candidates in people with spinal cord injury with certain characteristics; for example, all of them suffered their injuries from one to five years. All patients showed an improvement, which varied depending on the type of injury, its location, its magnitude, and time since it was suffered. Some patients were able to walk again, patients who did not control their sphincter muscles were able to control them, and kids with practically total paralysis could move their legs, Quintanar Stephano said.
Source: Agencia Informativa CONACYT