Could a diabetes drug help to treat Alzheimer's disease?
In a new paper published in the journal Brain Research, the researchers explain how the "triple-action" drug resulted in a significant reversal of memory loss in mice that were genetically engineered to develop human-like Alzheimer's disease.
The new drug "holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer's disease," says study leader Christian Hölscher, a professor in the Faculty of Health and Medicine at Lancaster University in the U.K.
Alzheimer's is a brain-wasting disease that accounts for 50–75 percent of cases of dementia, which is a condition wherein people gradually lose their ability to think, remember, make decisions, hold a conversation, and look after themselves.
As the disease progresses, the brain undergoes biological and chemical changes, and particular areas shrink as nerve cells, or neurons, die.
The exact causes of Alzheimer's are currently unknown, but microscopic examinations of affected brain tissue have revealed two hallmarks: abnormal accumulations of protein segments known as "plaques" and "tangles."
Current treatments make no real difference
The number of people with Alzheimer's disease is rising rapidly as the population ages. In 2015, there were an estimated 46.8 million people worldwide living with dementia, and this number is expected to reach more than 130 million in 2050.
In the United States — where Alzheimer's is currently the sixth leading cause of death — there are an estimated 5 million people living with Alzheimer's disease. This is expected to rise to 16 million by 2050, accompanied by a significant rise in costs.
To the U.S., the cost of Alzheimer's and other causes of dementia in 2017 was estimated to be $259 billion and is expected to rise to $1.1 trillion by 2050.
At present, there is no cure for Alzheimer's disease, and there are also no treatments that make a significant difference to the symptoms.
Drug raises activity of three growth factors
Type 2 diabetes is a disease that results from insulin resistance, a condition in which cells become less sensitive to insulin and therefore less able to take in glucose from the bloodstream to use as energy.
The pancreas makes more insulin to compensate, but eventually it will be unable to keep up and blood glucose levels will rise, leading to prediabetes, diabetes, and other health problems.
The drug that Prof. Hölscher and his group tested in the new study is a "triple receptor agonist" that activates the proteins that allow signals from three growth factors — called glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon — to enter cells.
Previous studies have revealed that type 2 diabetes is a risk factor for Alzheimer's, and problems with growth factor signaling have been detected in the brains of people with the disease.
The new study is the first to show that a triple receptor agonist may protect the brain from the progressive brain damage that occurs in Alzheimer's disease.
'Consistent neuroprotective effects'
The researchers tested the drug on aged APP/PS1 mice whose brains were in the advanced stages of degeneration. APP/PS1 mice are engineered "transgenic mice" that carry versions of human genes that are linked to an inherited form of Alzheimer's.
In a maze learning test, the treated mice showed improved memory formation. Also, examination of their brain tissue showed a reduction in amyloid plaques, inflammation, and oxidative stress.
Treated mice showed higher rates of new nerve cell generation and cell-to-cell connections, and increased levels of a growth factor called brain-derived neurotrophic factor, which protects nerve cells.
"These very promising outcomes," says Prof. Hölscher, "demonstrate the efficacy of these novel multiple-receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuroprotective effects in several studies."
He notes that clinical studies that used an older version of the same type of drug have already shown "very promising results in people with Alzheimer's disease or with mood disorders."
The researchers believe that their findings point to a "promising" direction in which to look for new treatments for Alzheimer's disease.
"Here we show that a novel triple receptor drug shows promise as a potential treatment for Alzheimer's but further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new drug is superior to previous ones."
Prof. Christian Hölscher