First, Dr. Donna J. Cross watched as Alzheimer’s robbed her grandmother of her independence, her personality, and ultimately, her life.
Now the disease has taken over the brain of his father-in-law, who now faces the same slow, heartbreaking deterioration.
It may be too late for them, but Dr. Cross wants to save the millions more diagnosed with this mind-debilitating disease.
She believes she is on the cusp of a breakthrough after a repurposed cancer drug caused the “complete reversal” of cognitive decline in mice with Alzheimer’s.
‘This is my passion. It started out being something personal for me; and still is, in the extreme,’ said Dr Cross.
Alzheimer’s disease is the most common cause of dementia, with an estimated 6 million Americans suffering from it.
Dozens of drugs to slow cognitive decline in dementia over the past decade have failed to show real benefit. Researchers have turned to well-established medications in hopes of taking advantage of what is already available to bring a viable Alzheimer’s treatment to patients as soon as possible.
Dr. Cross focused on Paclitaxel, a chemotherapy drug approved by the FDA in 1992.
It works by binding to a protein that forms the support structures of cells that help them divide and spread. By strengthening these structures, the drug can prevent cells from dividing into two new cells, which is how cancer grows.
The drug also activates certain pathways that end up killing damaged cells.
Dr. Donna Cross found that a chemotherapy drug reversed cognitive decline in mice with Alzheimer’s disease
Research conducted by Dr. Cross over the past decade has shown that it can also strengthen neuron structures that may become damaged over time as Alzheimer’s disease progresses.
The breakthrough was when he administered the drug through the nose to mice with Alzheimer’s.
The drug caused “a complete reversal of his cognitive deficit,” according to Deseret News.
The finding was a major victory for Dr. Cross and his fellow researchers, especially given the long list of failed drugs targeting a long-accepted feature of Alzheimer’s.
Focusing on a well-established cancer drug could usher in a new wave of drugs already approved to treat the disease in a much shorter period of time than it would take to develop a new drug, which may not even end up working, from scratch .
Dr Cross said: “If that were to happen in humans, we still have a lot of work to do,” adding that if it did happen, “it would be huge.”
“We will treat not only Alzheimer’s, but any type of dementia: ALS, Parkinson’s, multiple sclerosis, spinal cord injury, any type of disease where nerve cells are dying.”
You would need to create a version of the drug that could cross the human blood-brain barrier (BBB), which is no easy task.
The BBB is a network of blood vessels and tissue that serves as a protective layer that lines the inside of the brain, protecting it from toxic substances.
Many drugs cannot pass through this protective layer surrounding the human brain, which is a major obstacle for anti-cancer drugs, for example.
But Dr. Cross found that administering the drug through the nose was effective at crossing the BBB in mice and would presumably do the same in humans.
The next step is to prepare the drug for clinical trials, an expensive undertaking with a potentially invaluable return on investment.
She said: “Although it is too late for my grandmother and probably too late for my father-in-law, it is not too late for a large number of people in the world, which is why we have to keep moving forward.”
He earned his doctorate in neuroscience at the University of Michigan in search of a cure.
He then moved on to the University of Washington and finally to the University of Utah, where he currently directs the neuroimaging and biotechnology laboratory.
The graph above shows how the death rate from Alzheimer’s disease has increased in the United States. This may be related to more older people living longer
That’s where Dr. Jindrich (Henry) Kopecek and Dr. Jiyuan (Jane) Yang came in.
Both university chemists had offices located next to Dr. Cross’s, which had been placed there simply because there was space.
He began a collaboration with them to develop the drug and prepare it for clinical trials.
Dr Cross said: ‘These guys are rock stars. I came to them as a person with brains interested in the treatment of neurological conditions, and they are the people who develop and distribute drugs. “It’s a very strong collaboration because of our different areas of expertise.”
An estimated six million Americans suffer from Alzheimer’s, most of whom are age 65 or older.
Currently, there is no cure for Alzheimer’s, although there are treatments that can slow the progression of the disease.
It is thought to come from the buildup of sticky proteins in the brain called beta amyloid.
A brain affected by Alzheimer’s disease overproduces the precursor proteins that generate beta amyloid, which appear in abnormal forms that clump together.
These clumps disrupt normal neuronal function and alter cell signaling pathways, eventually killing cells.
But drugs targeting amyloid have repeatedly failed, showing minor benefits while increasing the risk of brain hemorrhages, calling into question the general orthodoxy about the causes of Alzheimer’s and the best way to stop its progress in destroying brain cells.
Dr. Cross will present her research at the Alzheimer’s and Caregiving Education Conference this week.