Israeli scientists have found a drug that holds promise for a range of brain diseases, including Alzheimer’s, but you may want to hold your hopes for a few years or so.
Drug discovery is hardly a smooth path, but the hunt for drugs to treat Alzheimer’s disease has been particularly frustrating, leaving a trail of smoking corporate corpses and frustrated researchers in its wake. Cambridge, Mass.-based startup Satori Pharmaceuticals closed its doors in May after its flagship candidate drug proved disastrous in animal trials, unexpectedly interfering with the adrenal glands of lab monkeys. Irish drugmaker Elan Corp. was also severely shaken after its Alzheimer’s drug bapineuzumab failed in the final stages of human testing, but was rescued by a $8.6 billion buyout by Michigan-based Perrigo Co. in July. Drug giants like Eli Lilly and Baxter International have also seen potential Alzheimer’s treatments flounder in recent years.
"I think we fundamentally lack an understanding of the pathogenesis of this disease," Jeff Jonker, former chief business officer at Satori, told Fierce Biotech in May. "And because we lack an animal model that replicates the human biology, we really are flying blind preclinically."
So it's best to have a grain or two of salt handy when you read about new Alzheimer’s research. Still, recent results from an aging research team led by Hebrew University School of Medicine biologist Ehud Cohen are intriguing.
Cohen and his colleagues think that blocking a signaling pathway involving insulin and the growth hormone IGF1 could be a way to treat degenerative brain diseases and slow other aging-related conditions. One common feature in late-onset brain conditions like Alzheimer’s, Parkinson’s disease, and Huntington’s disease is the accumulation of odd proteins. While the proteins suspected in each disease are different, they all tend to emerge around the same time late in life. And the insulin-IGF pathway seems to play some role in the ill effects from these toxic protein accumulations.
Scientists have been able to extend the lives of mice and nematode worms by reducing the activity of the insulin-IGF pathway through genetic modification. But with adult humans, you can’t just reach in and rewire the genome after the fact (at least, not yet). You have to find a drug that accomplishes the same reduction in the signaling pathway.
In an initial study with a drug called NT219 -- originally developed as a cancer treatment -- reported in the journal Aging Cell in November, Cohen and his team tried the compound out in nematode worms. They found that NT219 helped mitigate the effects of accumulated proteins linked to a degradation of brain function -- a promising, yet early-stage find.
“The road from worms to humans is a long one,” Cohen told Haaretz this week. “We recently got the go-ahead to proceed with a study on mice that will start in a few weeks.” But “at this point, it looks like a promising step in a totally new direction, in which research has been done in the field for less than a decade.”
While patients wait for drugs to make it through clinical trials, some researchers are looking for other ways to make life a bit easier for Alzheimer’s sufferers. One potential treatment involves delivering tiny electric shocks into a patient’s brain, via wires threaded through holes drilled in the skull. These minute shocks may jumpstart brain connections clouded by the disease, but the treatment’s long-term effectiveness and effects remain to be seen.