About 5.1 million Americans battle with Alzheimer’s, a disease that is as mystifying as it is devastating. Researchers still don’t know how the disease begins, but watching a loved one deteriorate from Alzheimer’s is a long and painful process. Just ask Donna Sainato.
“We lost our dad 9 years ago to Alzheimer’s, and he was fairly young — he was in his 70s, and then 5 years ago my mother was diagnosed with Alzheimer’s and she now resides in a nursing home,” said Sainato.
Knowing that she will lose another parent to Alzheimer’s is something Donna and her siblings find themselves coming to terms with every day. Feelings of sadness and helplessness ebb and flow, depending on how good or bad the day is going for their mother. Meanwhile, researchers continue trying to find a drug, a device — something that will offer a glimpse of hope into how to address this disease. Recently, scientists announced that they may be able to offer such hope.
At the Draper Lab, scientists have found a way to recreate the human brain on a tiny lab chip. Shankar Sundaram, director of the Draper Bioengineering Center in Tampa, Fla., says this brain-on-a-chip could accelerate research into Alzheimer’s, Parkinson’s and other neurodegenerative diseases.
“To accurately represent the brain for the purposes of drug discovery and development, we needed to reproduce various facets of it,” said Sundaram.
The work they’re doing is part of the Draper Laboratory’s BIO-MIMETICS program in Cambridge in collaboration with MIT.
“As we all know, we have a huge issue with pharmaceutical drugs being withdrawn either late in phase 3 clinical trials or after they’ve been marketed due to adverse events. And that costs upward of a billion dollars for pharmaceutical development,” Sundaram said.
Drug development is a long and risky process, and about one third of new drug candidates fail in advanced clinical trials. With an average $1.2 billion price tag to research and develop each new drug, there is a lot to lose.
Scientists at Draper are hopeful that brain-on-a-chip will more accurately test a drug in early development so that if something is amiss, it will be caught early on. This would dramatically reduce the failure rate of drugs in clinical trials and speed up the research process.
While this is all very exciting for the drug research community, there is some reservation. Dr. Sandy Auerbach, director of behavioral neurology at Boston Medical Center, says he is cautiously optimistic.
“I think that it’s very promising research and unfortunately, there’s a lot of promising research. And if I had a billion dollars to spend on research, this might very well be one of them. But there are a lot of things that are equally important,” said Auerbach.
Auerbach says that while he’s excited by what brain-on-a-chip means for the advancement of drug development, he’s more concerned about coming up with ways to detect Alzheimer’s earlier.
“One of the big things is developing more precise reliable biomarkers. Things like not relying on someone’s memory to assess who is going to develop the disease. By the time patients and doctors become aware clinically, the disease has been developing for years,” Auerbach said.
With the rapidly aging boomer generation, there is a sense of urgency in detecting the disease early, as well as having successful drug development. At Doris Garnhum’s dining room table in Chelmsford, she and her sister Donna Sainato express concern about their own future.
“We joke about it, but we’re frightened of it,” Garnhum added, absentmindedly running the palm of her hand over the red plaid tablecloth. “I mean, we’ve seen it, so we know what it is. And we know that you walk in a room and you don’t know the people.”
Her sister chimes in. “As you age, you start having lapses in your memory,” Sainato said. “And so when you forget something or you’re in the middle of something, you forget what you’re doing, you say, 'Omigod, I probably have Alzheimer’s!' And it probably isn’t … but when both your parents have it, it’s like, when’s it going to start?” Sainato said.
As their mother Phillis Lovett’s condition worsens, Donna, Doris and their siblings have channeled their pain and loss into raising money for research. They started the Lovett’s League, a foundation to raise awareness, and are throwing a Halloween fundraiser at the end of the month to benefit the Alzheimer’s Association.
“I want people to realize that there are 5 million people out there diagnosed with Alzheimer’s, there are 80 million baby boomers out there that are aging,” Sainato said. “Everybody needs to be concerned about this disease. This is something that could cripple our healthcare system.”
This is something on the minds of families and researchers alike, which is why time is of the essence. Right now, a lot of early drug research for neurological diseases is tested on cells in a petri dish.
Back at the Draper Lab, Shankar Sundaram said having an exact replica of the brain will help them better understand how drugs work, and ultimately how diseases such as Alzheimer’s develop.
“Putting different cell types together is known, but what we wanted to do was put them in a physiologic microenvironment,” Sundaram said. “In other words, if there was a person living in a certain society, they function and behave in a certain function. If I just pick them up and put them in a colony in the moon, they are likely to act completely differently. So that is the paradigm missed in a lot of studies.”
What Sundaram is saying is if they know exactly how the brain acts, they’ll know how it responds to drugs. He believes brain-on-a-chip could revolutionize the way drugs are tested.
“It’s a human model system that ultimately we hope in the next 3 to 5 years will revolutionize drug discovery in terms of being adopted by the industry,” Sundaram said. “In terms of being the definitive tests where drugs must pass safety and efficacy benchmarks before they are moved onto clinical trials.”
Back in Chelmsford, where it’s getting late, Garnhum and Sainato brighten up when they talk about their Halloween fundraiser. They say it’s how they can contribute to research, and it’s what helps their family cope with what’s ahead.
“You’re never prepared,” Sainato said. “And we know — we truly know what’s going to happen.”
“You can’t fall apart,” Garnhum added. “Because that’s not going to get you anywhere. I mean you just have to keep going. Try to be positive and do things like we’re doing — that’s positive to me,”
“Yeah, yeah,” said Sainato. “That makes me feel good.”
