UPDATED — The first New Year’s Janie Carney spent with the man who would become her husband, he told her it was time to make a list of what they wanted to accomplish in 2003.
“No one had ever asked what I wanted in life,” she said.
But Frank Carney did. The Pizza Hut co-founder made resolutions every year.
“He’d start talking about it after Christmas.”
Until 2009, when he didn’t say anything.
So Janie Carney printed a list with categories such as careers, philanthropy and spirituality and laid it on the kitchen table.
“It sat there for two weeks,” she said. “Never said a word about it.”
She’d noticed other oddities in her husband’s behavior, such as when he tried to pour more wine for guests whose glasses were already full.
Carney said her creeping concern turned into something frighteningly different.
It was the beginning of a spiral of doctor appointments, an eventual Alzehimer’s disease diagnosis and her despairing attempts to get her husband in the best-possible clinical trials.
That led to physician Daniel Alkon, president and chief scientific officer at New York-based Neurotrope Inc., and Carney’s introduction to Bryostatin-1.
Bryostatin-1 is not a statin but a chemical compound made by bacteria that live on tiny creatures in the ocean. It initially was used to treat cancer, but Alkon was using it in a couple of compassionate-care trials — the kind of clinical research that is done when nothing else has worked for a patient.
Carney lobbied for her husband to be part of one of those trials. It took 17 months from her first call with Alkon to the day her husband started the trial.
“This was a woman not to be denied,” said Mike Good, director of Ascension Via Christi Research.
Good conducted the trial in Wichita based on protocols established by Alkon. Good then made modifications based on Frank Carney’s responses.
Before that could happen, though, Janie Carney had to ask her husband if he wanted to participate.
“He looks at me and says, ‘What for?’ That’s typical of Alzheimer’s.”
Thirty minutes later, he came back to her.
“Would it help other people?” he asked.
“That’s Frank Carney,” his wife said. “That was his goal. My goal was to save my husband. To take any chance I could.”
As a young medical student at Cornell University in the late 1960s, Alkon had his interest piqued by how memory sometimes goes wrong, not only in Alzheimer’s patients but in other cases, such as with people who have Parkinson’s disease or who have had strokes.
“They all involved, in some way, pathologies of memory,” he said. “We didn’t really understand on a molecular level.”
Alkon said he wanted to understand how memory works in order to help restore and rebuild it.
“That was my driving force and still is.”
Good said the brain is an “impeccably designed organ that will make you believe in God.”
He said it is so intricate, it will probably take a combination of agents treating various areas of the brain to help people with their memories.
In Alkon’s research, he identified a critical molecular master switch for memory storage — an enzyme called protein kinase C epsilon — that orchestrates new synaptic structures in healthy brains and prevents the death of neurons.
He said he wondered if it might do the same for brains whose wiring was suffering.
“That was the jump that we made,” Alkon said. “It was an aha moment.”
He and his team looked for any known chemical to activate that master switch. They found it in Bryostatin-1.
Alkon said the National Cancer Institute then provided millions of dollars worth of it that was purified for human use.
The first two Bryostatin-1 trials on Alzheimer’s patients were on a 95-year-old and an almost incapacitated 31-year old. Alkon wanted to find “someone gone but not as far gone.”
“That’s how we found Frank Carney,” he said. “With Frank, we could do something that we hadn’t been able to do.”
That was to measure his blood and see how much benefit corresponded to the medication, “which was a big step forward for us,” Alkon said.
He used quantitative psychometrics, which measure someone’s cognitive function and mental capacities with well-established metrics.
Good and his team at Ascension were the ones taking samples, and Alkon worked with them remotely, but it was Janie Carney who often was the best barometer of her husband’s progress.
“There were things that we didn’t really understand but Janie very much understood,” Good said.
One day, Frank Carney went to the day room of his care home and picked up a pool cue, angled a ball and shot it.
“Janie’s going, ‘He’s playing pool! He’s playing pool!’ ” Good said.
That compared to a nearly-mute Carney sitting in a chair and staring at the ceiling hallucinating a week earlier.
“What we saw within the first couple of weeks is that Frank got remarkably better,” Alkon said. “Instead of hallucinating, he started to be able to feed himself, dine with his wife, talk to his wife.”
His cognitive score went from a 3 to a 12. The average person has about a 30.
“It was nothing short of miraculous,” Good said of the first infusion. “It was surreal because we didn’t understand what had just taken place completely. . . . No one expected that immediate of a response.”
However, it was not like turning on a light switch that stays on, he said. Dosing was an issue, and in subsequent weeks the benefit went down.
There were interesting twists. Sometimes the smaller the dosage the more effective the treatment.
Good said there was “a real opportunity for research” because Frank Carney’s overall health was strong with no compromised organs.
“What I had was a Lazarus,” Janie Carney said. “I had Lazarus for a year. We could do things again.”
Then it abruptly ended, not because the trial was done but because the care facility where Carney was living would no longer keep him as a patient. Janie Carney said that’s another story entirely.
Regardless, the trial was over. Alkon said it couldn’t continue because there are rigorous specifications in trials that require complex planning.
“It’s not so simple,” he said. “We were very frustrated. We would have liked to have continued.”
He said he believes Carney could have kept improving.
“We saw some remarkable improvement. . . . We learned an amazing amount. Did we want to learn more? Of course.”
Alkon said there’s “no question at all” that Frank Carney at least met his goal with the trial.
“Absolutely he has helped other people. Both he and Janie.”
Throughout his career, Alkon said he didn’t believe it would be possible to replace wiring in a brain.
“I would say that’s not the way God designed us.”
He now has proof in mice. Through necropsies, researchers can see how the wiring has returned.
In humans, researchers so far can only infer the wiring has returned and approximate it.
“Right now, there’s no way to measure that wiring in a living person, and that is what we need to do,” Alkon said.
It won’t happen until an autopsy is performed on someone from one of his trials.
Alkon used information from the first three compassionate-care studies to design a new trial protocol with 150 advanced Alzheimer’s patients and learned even more. He’s now doing a 100-person confirmatory trial.
“If we get what we’ve already seen, we believe it will be a breakthrough in the field,” Alkon said.
“That kind of improvement . . . has not really been seen in the 100 years since the disease was first described.”
The next step would be to work with the FDA to discuss how to proceed.
Patients in earlier stages of Alzheimer’s also need to be tested, and studies need to be done for longer periods, Alkon said.
He wonders if a complete reversal is possible.
“I think there’s a chance that that may happen.”
Good said even the chance of it is crucial for patients and their families who are battling the disease.
“The bottom line here . . . is all about the hope.”
Frank and Janie Carney met while sitting at separate tables in the Ya Ya’s bar. They started talking and never stopped.
“It was so instant,” Janie Carney said. “Our relationship was built on an auditory love language. I fell in love with him in our conversations.”
Now, Frank Carney is in the late stages of Alzheimer’s. His words are raspy and labored if they come at all.
Janie Carney said there are other ways to communicate.
“The way he holds my hands, the way he still puckers to kiss me. Sounds. I can nuzzle his ear and he nuzzles back.”
Carney said she thinks “this disease is like slipping into a coma.” Just as people in comas can sometimes have an understanding of what’s happening around them and who is caring for them, Carney believes Alzheimer’s patients do, too. She said Bryostatin-1 gave her that proof.
During the peak of her husband’s progress with the trial when he had more cognitive ability, Carney said he was able to talk to her from across the room, unlike worse times when he spoke only when he was immediately next to her.
Once during this good time, he called to her from across their hearth room.
“I just want you to know how much I love you,” he said.
“He was thanking me,” Carney said.
“He was thanking me for not giving up.”
For information on Alzheimer’s disease call the Alzheimer’s Association at 1.800.272.3900 or check www.alz.org.