A team of scientists has developed a potentially ground-breaking dementia drug that could prolong the life of brain cells and could mark a new frontier in the treatment of the disease.
Scientists from Ontario, Stanford University and the University of California found that one pill twice a day could reduce levels of a harmful brain protein called amyloid, one of the main hallmarks of the disease, by almost 10 per cent.
Experts say benefits to patients’ brains were seen after just six months of treatment with the drug, as opposed to years as with other experimental treatments.
Additionally, side effects were few and mild, the most common being diarrhea and headaches.
Other novel dementia therapies in development, such as donanemab, have raised concerns among experts because of the known risks of brain hemorrhages, which have killed several trial patients.
The new drug, called LM11A-31, targets a specific receptor called P75NTR in the brain that helps regulate the survival and development of brain cells.
When cells or neurons die, messages cannot be transmitted through the brain as effectively, which scientists believe is what causes the thinking and memory difficulties in dementia.
He results A recent trial, published earlier this month in the journal Nature Medicine, found that LM11A-31 improved signaling between the receptor and cells to promote growth and survival.
The drug is the first to study a therapy targeting P75NTR and was found to significantly slow the buildup of amyloid, a protein characteristic of Alzheimer’s, in patients’ brains.
The researchers said the drug is “exciting” because it directly improves the ability of the brain’s neurons to survive.
Alzheimer’s disease is the most common form of dementia, affecting 6.7 million Americans. With the aging population booming in the United States, that number is expected to rise to 13 million by 2050.
While the root cause of Alzheimer’s disease is still debated, scientists believe the damage is likely the result of an abnormal buildup of proteins (amyloid and tau) in and around brain cells.
In Alzheimer’s patients, amyloid proteins are not effectively cleared from the body and eventually form plaques in the brain. Tau proteins detach from neurons forming tangles.
Both can cause the death of neurons, making it difficult to transmit signals throughout the brain.
Canadian and California researchers studied LM11A-31 in 242 participants with a confirmed diagnosis of mild to moderate Alzheimer’s over a 26-week period.
They took samples of cerebrospinal fluid (CSF) from the study participants to measure the level of amyloid present. CSF is a fluid that surrounds and protects the brain and spine.
In people who received the pill twice a day, the average amyloid buildup was up to nine percent less than in the CSF of people who received the drug.
The study says: “Overall, these findings indicate that LM11A-31 slowed or reversed AD-related longitudinal increases (CSF amyloid).”
The graph above shows the estimated projection of Alzheimer’s disease patients in the US through 2060.
When measuring long-term changes in CSF tau levels between the two groups, the researchers found no significant differences.
The researchers acknowledged the limitations of the study, which included a limited time period and a small group of participants. Therefore, their ability to assess any differences in cognitive changes was limited.
However, the researchers said the results of their study are promising because such significant findings are not typically seen in such early studies, and most research takes two or more years to produce such results.
Study co-author Hayley Shanks, Ph.D. in neuroscience. student at the University of Western Ontario, saying: ‘The reason this drug is interesting is because it directly affects the ability of neurons to survive. It promotes their overall integrity, branching, and synapses (where cells connect and communicate with each other).
“In (preliminary) animal models, the drug was shown to preserve these neurons or reverse the damage, which translated into behavioral improvements, almost returning the neurons to a healthy state.”
Co-author Taylor Schmitz, a professor at the University of Western Ontario’s Faculty of Medicine, added: “The drug slowed the rise of this marker of inflammation in the cerebrospinal fluid.
“This is important because, over the past five years, inflammation has become a key factor in understanding Alzheimer’s disease.”
There is currently no cure for Alzheimer’s and new drugs in development such as donanemab only marginally slow the rate of progression and carry dangerous side effects such as brain haemorrhage.
While the drug was hailed early on as a potential therapy, a quarter of patients in the trial suffered brain inflammation and three people died from brain swelling or hemorrhage attributed to the drug.
Another drug, Leqembi, works similarly to donanemab, but can also cause amyloid-related imaging abnormalities (ARIAs), which are brain changes that can include bleeding and swelling.
It is approved by the FDA, but studies show that about 20 percent of people who take the drug develop ARIA, but only 20 percent of those people experience symptoms.
For decades, researchers have focused on developing drugs that target amyloid clumps, a hallmark sign of dementia.
However, recent focus has been on how tau proteins play a role in cognitive decline and there are currently at least six completed or ongoing clinical trials testing the safety and effectiveness of vaccines to treat and prevent Alzheimer’s disease targeting both tau and amyloid.
