New Alzheimer’s Disease Drug Is Capable of Repairing Synaptic Damage
Researchers from the Washington State University, have created a new synthetic drug that is reportedly capable of improving the cognitive function of laboratory rats that suffer from an Alzheimer-like mental disease. The compound contained in the newly synthesized drug is designed to repair the brain damage done by Alzheimer’s disease. This new compound is completely different from every drug on the market. Drugs that are currently available on the market can inhibit the enzyme called cholinesterase, which is suggested to be part of the learning process and memory development. Another class of drugs that is on the market is used to slow down the process of cellular death. According to professor Joe Harding, these drugs were not meant to rebuild the connection between neurons, thus are not capable of restoring the lost brain function. He said that this new compound is not meant to stop the evolution of the disability, but to repair the already damaged nerve connections.
The study was published in the Journal of Pharmacology and Experimental Therapeutics, having professors Joe Harding and Jay Wright as main authors, along with their research team from WSU. According to a recent publication from PhRMA (Pharmaceutical Research and Manufacturers of America), only 3 of the 104 newly developed drugs were approved for production, in the past 13 years.
“This 34 to one ratio of setbacks to successes underlines the difficulty of developing new medicines for Alzheimer’s”, said a representative from PhRMA. The new drug developed by the researchers from WSU is only in its first phases. Approval from the FDA (Food and Drug Administration) is required before progress can be made in its development.
Professor Harding said that the safety testing of the drug could cost almost $1 million. The research funds will be granted by M3 Biotechnology Inc., which is Harding’s and Wright’s company. Funds will be received from the Washington State University as well as from partnering pharmaceutical companies.
Harding and Wright have put in work for the development of this new compound since the early ’90s. Back then, they studied the impact of angiotensin IV (a hexapeptide from the angiotensin class) on the hippocampus. The role of the hippocampus is well known in short-term memory and spatial learning. They observed that angiotensin IV, which is usually linked, as all angiotensins, to the blood pressure regulation process, was capable of reversing the learning deficit that comes with different types of dementia.
Unfortunately, this new discovery was limited by the fact that the new drug candidates developed with the use of angiotensin IV were quickly destroyed by the organism, thus not being able to cross the blood-brain barrier. This barrier blocks the passage of molecules from the blood to the brain. Due to this impediment, direct application to the brain was the only practical solution.
“We said, ‘That’s useless. I mean, who wants to drill holes in people’s heads? It’s not going to work. It’s certainly not going to work for the big population”, recalled professor Harding.
Harding and Wright managed to create a smaller version of the compound approximately 5 years ago. They named it Dihexia. This new version was capable of crossing the blood-brain barrier, thus allowing the researchers to administer it as a pill. The new version of the compound was tested dozens of laboratory rats that were pre-treated with scopalamine (a tropane alkaloid drug that hinders a neurotransmitter that plays an important role in the learning process). According to the researchers, rats that were treated with scopalamine weren’t able to learn the location of a submerged platform in a water tank. However, after they administered this new compound, all of the rats were able to learn that specific location. The results were the same, regardless of the method used to administer the drug, be it orally, parenteral or directly applied in the brain.
Even though the study results are statistically significant, there is need for further testing in order to confirm that the newly discovered drug is effective. At this moment, the “gold standard” compound that is capable of creating new neuronal connections is the BDNF (Brain-derived neurotrophic factor). However, researchers suggest that Dihexa is almost 7 times more powerful than BDNF. In numbers this means that 10 million times as much BDNF would be required in order for it to have the same effect as Dihexa.
“We quickly found out that this molecule was absolutely, insanely active. These results further suggest that Dihexa or molecules like it may have applications in other neurodegenerative disease or brain traumas where neuronal connections are lost”, concluded professor Harding.
The in-depth study paper can be found here.