U.S. Patent 7,928,070 issued in April of this year for what was simply labeled as a “memory-enhancing protein.”
Todd Sacktor, a professor at SUNY Downstate in Brooklyn, and a panelist at the 2011 World Science Festival’s The Unbearable Lightness of Memory, received the patent just about a month after he and colleagues published an article in the journal Science that showed that the chemical, shortened to the cryptic PKM zeta, could shore up old memories in rats.
All of this would seem to suggest an inevitable progression: research leads to patent which leads to drug. That usually never happens. It will almost certainly be many years before the study reported in Science becomes a drug covered by patent 7,928,070. Drug development is always slow, but neurological drug development seems to proceed even more sluggishly, crawling along at the same pace as Aplysia, the snail genus often used to study memory.
The one thing that is a fair bet in this line of research is that something important will go wrong along the way. An earlier generation of memory studies that raised hopes for cognitive enhancement drugs illustrates the pitfalls.
In recent decades, scientists have pursued another approach to explore the neurological basis for learning. Long-term potentiation, as a key step in laying down a memory is called, represents a response by a brain cell to a particular input—whether visual, auditory, or an internal signal from another part of the brain. Inside a nerve cell, new proteins form and this cascading set of molecular events eventually ends up altering the structure of the synapse, the connection point between neurons. The physical change strengthens signals transmitted among neurons—and so a new memory is born.
These type of studies, carried out by a number of laboratories, and which led to a Nobel Prize for Eric Kandel, have yet to produce a new generation of memory-enhancing drugs, despite early expectations that they might soon do so. In 2004, Science magazine mentioned four new companies—Sention, Cortex Pharmaceuticals, Memory Pharmaceuticals, and Helicon Therapeutics. All four went on to face developmental hurdles and severe financial upheavals in bringing to market memory-boosting drugs to enhance long-term potentiation.
Sention is no more. Hoffman-LaRoche scooped up Memory at a penny stock price and both Cortex and Helicon have also faced similar debacles. In a 2009 article that I wrote for Scientific American, Tim Tully of Helicon put it this way: “The way I like to explain this to audiences when I give talks is that when Helicon was formed I thought that I was making memory enhancers for my parents and I had no gray hair. They’re now dead, I’m fully gray and I’m fully cognizant that this is a race for me not them.”
A drug that delivers PKMzeta to enhance memory or an inhibitor of the enzyme that could quell fearful recollections may confront their own set of technical issues. In a recent blog post at scientificamerican.com, Douglas Fields, a neuroscientist at NIH wrote:
“Like a Midas, cursed by having his wish granted that everything he touched would turn to gold, permanent retention of memories could be debilitating. This is because forgetting is just as important for learning as memory. Bad habits could not be overcome; skills would not be improved, information such as an old address or phone number, could not be updated, and traumatic events would never fade from the horror that overwhelms a person immediately after the trauma.”
Fields also interviewed Sacktor, who noted: “We don’t know what negative consequences there would be [for a drug that would enhance memory]. “For patients with amnesia, such as in neurodegenerative disease, the benefits might outweigh the negatives.” Even if drugs are not immediately forthcoming, though, the research on PKMzeta has already yielded benefits. It provides valuable new insights into how memories are stored over the long haul, the reason you can remember flinging your cap skyward at your college graduation or where exactly you were on 9/11.
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