First, Dr Donna J Cross saw Alzheimer’s rob her grandmother of her independence, personality, and ultimately her life.
Now the disease has taken hold of her father-in-law’s brain, who now faces the same slow and heartbreaking decline.
It may be too late for them, but Dr Cross wants to save the millions more diagnosed with the mind-wasting disease.
She believes she’s 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 personal to me; it still is, extremely so,’ said Dr Cross.
Alzheimer’s disease is the most common cause of dementia and an estimated 6 million Americans have it
Dozens of drugs to slow cognitive decline in dementia over the past decade have failed to show a real benefit. Researchers have turned to well-established drugs in the hopes of leveraging what’s already available to bring a viable Alzheimer’s treatment to patients as soon as possible.
Dr Cross honed in on Paclitaxel, a chemotherapy drug that was approved by the FDA in 1992.
It works by binding to a protein that makes up the support structures of the cells that help them divide and spread. By shoring up those structures, the drug is able to stop cells from dividing into two new cells, which is how cancer grows.
The drug also activates certain pathways that end up killing off damaged cells.
Dr Donna Cross discovered that a chemotherapy drug reversed cognitive decline in mice with Alzheimer’s disease
Research by Dr Cross over the past decade has shown it can also bolster the structures of neurons that can be damaged over time as Alzheimer’s disease progresses.
The big breakthrough when she administered the drug up the noses of mice with Alzheimer’s.
The drug caused ‘a complete reversal of their cognitive deficit,’ according to Deseret News.
The finding was a major win for Dr Cross and fellow researchers, especially given the lengthy trail of failed drugs that targeted a long-accepted hallmark of Alzheimer’s.
Zeroing in on a well-established cancer drug could usher in a new wave of already-approved drugs to treat the disease in a far shorter period of time than it would take to develop a novel drug, that might not even end up working, from scratch.
Dr Cross said: ‘Whether that would happen in humans, we have a lot of work still to do,’ adding that if it did, ‘It would be huge.
‘We would treat not just Alzheimer’s, but also any kind of dementia: ALS, Parkinson’s, multiple sclerosis, spinal cord injury, any kind of condition where nerve cells are dying.’
She would need to create a version of the drug that could cross the human blood-brain barrier (BBB), which is no easy feat.
The BBB is a network of blood vessels and tissue that serves as a protective layer lining the inside of the brain, shielding it from toxic substances.
Many medicines can’t cross this protective layer around the human brain, a significant obstacle for cancer drugs, for instance.
But Dr Cross discovered that administering the drug up 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 priceless return on investment.
She said: ‘Even though it’s too late for my grandmother and likely too late for my father-in-law, it’s not too late for vast, vast numbers of people in the world, that’s why we have to keep moving forward.’
She earned her doctorate in neuroscience at the University of Michigan in pursuit of a cure.
She then went to the University of Washington and finally to the University of Utah, where she currently heads the neuroimaging and biotechnology laboratory.
The above graph shows how the death rate from Alzheimer’s disease has risen in the United States. This may be linked to more older people living longer
That’s where Dr Jindrich (Henry) Kopecek and Dr Jiyuan (Jane) Yang came in.
Both chemists at the university had offices situated next door to that of Dr Cross, who had been placed there simply because there was space.
She began a collaboration with them to develop the drug and get it ready for clinical trials.
Dr Cross said: ‘These guys are rock stars. I came to them as a brain person who was interested in treating neurological conditions, and they are the drug developer/drug delivery people. It’s a collaboration that is very strong because of our different areas of expertise.’
An estimated six million Americans have Alzheimer’s, most of whom are 65 or older.
Currently, there is no cure for Alzheimer’s, though there are treatments that can delay disease progression.
It’s believed to stem from the build-up of sticky proteins in the brain called beta amyloid.
A brain stricken with Alzheimer’s overproduces the precursor proteins that generate amyloid beta, which come in abnormal shapes that clump together into clusters.
These clusters disrupt normal neuronal function and disrupt cell signaling pathways, eventually killing cells.
But drugs targeting amyloid have failed repeatedly, showing minor benefit while also raising the risk of brain bleeds, calling into question the general orthodoxy about what causes Alzheimer’s and how best to halt its progress in killing off brain cells.
Dr Cross will present her research at the Alzheimer’s & Caregiving Education Conference this week.
