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New drug could treat Alzheimer’s decades before symptoms begin – Study Finds

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Dec 4, 2020

CLEVELAND — For some patients dealing with Alzheimer’s disease, the first noticeable signs of mental decline don’t appear until it’s too late to really fight off the condition. Now, scientists in Ohio say they have developed a drug that may treat the most common form of dementia decades before symptoms even appear.

A team from Case Western Reserve University says their new treatment targets the first signs of the devastating illness, chemicals buildups which kill neurons and fuel brain inflammation. Catching the disease early is believed to be vital for preserving memory and thinking skills.

“This is a missing part of the puzzle. We have discovered a pathway that is accessible to detection and potential treatment, prior to much of the disease’s damage and well before clinical symptoms appear,” lead author Dr. Xin Qi says in a statement.

Protecting the nerves in the brain

In experiments on mice, a small molecule called a peptide inhibitor put the brakes on mental degeneration. It destroys the protein DRP1, part of the pathway that reduces myelin. This is the protective sheathing for nerves, especially in white matter that help brain cells communicate.

The Case Western team confirmed the discovery in post-mortem brain samples of Alzheimer’s patients. They have already patented the medication. The researchers hope manipulating the pathway with medications will save the myelin-producing oligodendrocytes (OLs).

Alzheimer’s eventually leads to dysfunction and eventual death of the brain cells. This causes the patient to deal with growing confusion and lack of memory before their death.

“There is a growing body of evidence in the field that Alzheimer’s develops much earlier than previously thought, most likely decades before our current ability to clinically diagnose the condition,” study co-author Dr. Andrew Pieper says.

“Detecting the disease – and potentially treating it – at earlier stages will be critical to our battle against its devastating effects. The new pathway uncovered by Dr. Qi’s laboratory 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 and other forms of dementia develop when rogue proteins (amyloids beta and tau) clump together and kill nerve cells. The main risk factors include age, genetics, and a previous traumatic brain injury.

The study in Science Advances offers hope of a therapy that conserves them before the defining pathological breakdowns begin. A treatment could offer hope of screening patients under 50 who may be at risk for dementia later in life.

Last year, a study revealed vulnerable patients have more tau protein in their spinal fluid up to 34 years before they show signs of memory loss. The new findings show for the first time that OLs go awry due to the over expression of Drp1, slowing brain signals. The OLs are virtually gone before the familiar symptoms of Alzheimer’s become apparent in most patients.

Eliminating Drp1 in the lab rodents corrected the OLs, prevented inflammation, and lessened tissue damage. The animals also did better in cognitive challenges testing their ability to remember how to get around a maze.

“Our results show promise that targeting the Drp1-HK1-NLRP3 pathway and reducing the expression of the Drp1 protein could help reduce the downstream cascade of abnormal brain functions associated with the progression of Alzheimer’s,” Dr. Xin Qi explains. “If therapies targeting this pathway can slow, stop or even reverse early stage Alzheimer’s progression, then possibly there can be a reduction or delay to later stage damage and impairments.”

Getting ahead of dementia

One of the reasons researchers believe previous drugs trials have failed is because they are given to participants too late. Most Alzheimer’s diagnoses are made in patients over 65. Identifying it in younger patients can be difficult. Many have already experienced a significant loss in white matter, which is central to cognition, emotion, and consciousness.

“Identifying how Alzheimer’s unfolds in its earliest processes will help scientists better understand how to focus research into potential solutions for patients,” Dr. Pieper adds. “The Qi lab’s findings may help in targeting it earlier, potentially leading to better management of its symptoms and progression.”

Pieper says there have only been a small number of medications for Alzheimer’s approved since the disease’s discovery in 1907.

“While these medicines augment neurotransmission to provide temporary symptomatic benefit, they do nothing to slow disease progression. Identification of earlier approaches to treating Alzheimer’s – such as this research – is critical for society as the magnitude is growing explosively with our ageing population,” Pieper concludes.

SWNS writer Mark Waghorn contributed to this report.

 

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