Tetra’s experimental med may boost memory after brain injury

Brain imaging

New research coming from the University of Miami and Boston-based Tetra Discovery has found that the biotech’s experimental drug PDE4B could help brain injury patients with memory problems.

The drug, an inhibitor of phosphodiesterase 4 (PDE4) subtype PDE4B, is currently in Tetra’s pipeline for a range of brain-associated disorders, including schizophrenia and depression, as well as brain microglia involved in brain inflammation.

Tetra is testing its theory that addressing the functioning of PDE4s will enhance memory formation in brain neurons and nerve dendrites involved in these types of diseases.

University of Miami researchers have now teamed up with Tetra to assess whether this candidate could also help those with brain injuries caused by external trauma.

This has become an increasingly hot topic in the media in recent years given the publicity over American football and its record on players suffering from long-term conditions after head trauma, with the recent film Concussion, starring actor Will Smith, also doing much to highlight this issue.

This research was in fact helped by the Miami Project--an R&D-led group of scientists established 30 years ago by Hall of Fame linebacker Nick Buoniconti, after his son sustained a major spinal injury playing football.

But it is not just related to professional athletes as, according to the CDC, traumatic brain injury (TBI) is the leading cause of death and disability in those aged under 45, and a staggering 5 million Americans live with chronic disability as a result--with the cost of these injuries estimated to be around $76.5 billion a year.

This means that there is a high, unmet medical need for a therapeutic in this area, with many patients being given the long-marketed Alzheimer’s drug Aricept (donepezil) from Pfizer ($PFE) and Eisai to try to help manage their condition--a treatment, however, that has not been approved for TBI.

During their research, the authors, who published their findings in this month’s Journal of Neuroscience, assessed how these injuries impacted the brain, and showed that when it is damaged, the brain stops a certain protein that helps with memory, known as CREB, from doing its job.

Digging deeper, the scientists showed that when the brain is functioning normally, CREB is boosted by the cAMP molecule, but in an injured patient, this molecule too is dampened by trauma.

But the PDE4B inhibitor can increase cAMP levels, and therefore CREB, and in an animal study it reversed some of the memory problems sustained as a result of damage, as well as even helping the rats--who had spent 12 weeks with a brain injury and no treatment before being given the PDE4B inhibitor--with certain learning tasks.

This is not the first time PDE4s have been used to help brain injuries with other experimental meds, such as rolipram--also a selective phosphodiesterase-4 inhibitor that was first discovered by Schering AG back in the 1990s--having already been studied in TBI animal trials. Clinical tests of this class of drug have also been conducted in a number of lung diseases, such as asthma and COPD. 

But some of these previous PDE4 studies have been marred by side effects such as severe sickness, headache and diarrhea. The authors stressed, however, that they managed in their animal study to help improve memory and learning--but, crucially, without causing these side effects.

“Treating TBI survivors during the months to years after brain trauma is a very promising area of research and several clinical trials are already tackling this problem, by using drugs repurposed from other neurological disorders such as Alzheimer’s disease,” said Dr. Dalton Dietrich, scientific director of The Miami Project.

“This selective PDE4B inhibitor from Tetra Discovery Partners has great promise, restoring the learning and memory performance of TBI animals to nearly non-injured levels. This project represents an excellent example of a collaboration between academic researchers studying animal models of brain injury and a biotech company with expertise in human clinical trials. We expect that this collaboration with Tetra will yield a new clinical trial using this therapeutic strategy in human TBI survivors.”

- read the release