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CLEVELAND – For some patients with Alzheimer’s disease, the first visible signs of mental decline do not appear until it is too late to truly fight the disease. Now Ohio Scientists Say They’ve Developed Drug That Could Treat Most Common Form of Dementia decades even before symptoms appear.
A team from Case Western Reserve University said their new treatment targets the early signs of the devastating disease, build-ups of chemicals that kill neurons and fuel brain inflammation. Catching the disease early is considered vital for preserving memory and thinking skills.
“It’s a missing part of the puzzle. We have discovered an accessible pathway for detection and potential treatment, before much of the disease damage and long before the onset of clinical symptoms, ”says lead author Dr. Xin Qi in a statement.
Protect the nerves of the brain
In experiments with mice, a small molecule called a peptide inhibitor held back mental degeneration. It destroys the DRP1 protein, part of the pathway that reduces myelin. This is the protective sheath of the nerves, specifically the white matter that helps brain cells communicate.
The Case Western team confirmed the finding in postmortem brain samples from patients with Alzheimer’s disease. They have already patented the drug. The researchers hope that manipulating the pathway with drugs will save myelin-producing oligodendrocytes (OL).
Alzheimer’s disease ultimately leads to brain cell dysfunction and eventual death. This causes the patient to face increasing confusion and lack of memory before his death.
“There is a growing body of evidence in the field that Alzheimer’s disease develops much earlier than previously thought, probably decades before our current ability to clinically diagnose the disease,” says the co-author. of the study, Dr. Andrew Pieper.
“Detecting the disease – and potentially treating it – at its early stages will be essential in our fight against its devastating effects. The new pathway discovered by Dr. Qi’s lab could be targeted for therapy before the disease has progressed to the point of causing cognitive problems.
The threat of Alzheimer’s can last for years
Alzheimer’s disease and other forms of dementia develop when unwanted proteins (beta amyloid and tau) clump together and kill nerve cells. The main risk factors are age, genetics, and previous traumatic brain injury.
The study in Scientific advances offers the hope of a therapy which preserves them before the onset of the determining pathological breakdowns. Treatment may offer hope of identifying patients under 50 who may be at risk for dementia later in life.
Last year, a study found that vulnerable patients had more tau protein in their cerebrospinal fluid up to age 34 before showing signs of memory loss. The new findings show for the first time that LOs go awry due to the overexpression of Drp1, slowing brain signals. OL virtually disappeared before the familiar symptoms of Alzheimer’s disease became apparent in most patients.
Elimination of Drp1 in laboratory rodents corrected OL, prevented inflammation, and reduced tissue damage. The animals also did better in cognitive challenges testing their ability to remember how to move around a maze.
“Our results show that targeting the Drp1-HK1-NLRP3 pathway and reducing expression of the Drp1 protein may help reduce the downstream cascade of abnormal brain functions associated with the progression of Alzheimer’s disease”, explains Dr. Xin Qi. “If therapies targeting this pathway can slow, stop or even reverse the progression of early-stage Alzheimer’s disease, then there may be a reduction or delay in damage and impairment at the later stage.
Get ahead of dementia
One of the reasons researchers believe past drug trials have failed is because participants are given too late. Most Alzheimer’s diagnoses are made in patients over 65 years of age. It can be difficult to identify it in younger patients. Many have already experienced significant loss of white matter, which is central to cognition, emotion, and consciousness.
“Identifying how Alzheimer’s disease unfolds in its early stages will help scientists better understand how to focus research on potential solutions for patients,” adds Dr. Pieper. “The results from the Qi Lab may help target him earlier, potentially leading to better management of his symptoms and progression.”
Pieper says there have been only a small number of drugs for Alzheimer’s disease approved since the disease was discovered in 1907.
“Although these drugs increase neurotransmission to provide temporary symptomatic benefit, they do nothing to slow the progression of the disease. Identifying past approaches to treating Alzheimer’s disease – like this research – is essential for society, as their scale grows explosively with our aging population, ”concludes Pieper.
SWNS writer Mark Waghorn contributed to this report.
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