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Another Promising Asthma Drug for Alzheimers? - Zileuton/ Zyflo
Posted: Thursday, March 14, 2019 6:37 PM
Joined: 2/17/2019
Posts: 380

Singular is a leukotriene receptor antagonist, Zileuton also affects leukotrienes.


 Using a 22-year-old asthma drug, a Temple University research team was able to reverse signs of Alzheimer's brain damage and improve thinking ability in mice.

The team, led by Domenico Praticò, director of the Alzheimer's Center at Temple, gave zileuton to mice engineered to develop one of the hallmark proteins found in the brains of people with Alzheimer's disease.  After 16 weeks on the drug, also called Zyflo, the mice were found to have 50 percent fewer tau tangles than mice that had not received the drug.  The synapses, or connections between the brain cells, of the treated mice looked normal, while untreated mice had severe deterioration.  The treated mice also performed better on a maze test of memory.

In recent years, most drug research to combat Alzheimer's disease has focused on amyloid, the other misformed protein found in people with the condition.  So far, those attempts have been disappointing.  Increasingly, researchers are exploring other pathways to treat the deadly form of dementia. Praticò said a couple other drugs aimed at tau are also currently being tested.

Mouse studies are notoriously frustrating.  Many treatments that have looked promising in mice fail to work in humans.

Nonetheless, Praticò said that many previous mice studies attempted to prevent dementia.  This one involved mice that were already showing symptoms of dementia. That's an important distinction because most people are not diagnosed with dementia until brain damage has already occurred.

"It's very, very exciting," Praticò said of the study results. "This could be the first time that we could do a treatment."

The study was published online Friday in the journal Molecular Neurobiology.


Lane Simonian
Posted: Friday, March 15, 2019 9:59 AM
Joined: 12/12/2011
Posts: 5108

I am sure Larry that will be here in a few days to offer his perspective, but in the meantime I will give mine now.

Here is the best case scenario for targeting leukotrienes for the treatment of Alzheimer's disease:

Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage


 LTC4 inhibitors, commonly used for asthma, could find broad clinical use in major human pathologies associated with ER stress-activated NOX4 (NADPH Oxidase 4).

The problem is that there are many factors that lead to oxidative DNA damage in Alzheimer's disease.  Some of these factors such as amyloid oligomers, various herpes viruses, and leukotrienes themselves are a product of oxidative stress in the first place and then turn around and create more oxidative stress via g protein-coupled receptors.

If just one factor is causing the damage and you remove that factor you solve the disease early on.  That is why removing amyloid oligomers from mice always seems to cure "Alzheimer's disease" in mice because that is the only factor that the mice are "exposed" to.  

If a person has asthma or otherwise has high levels of leukotrienes, then this make sense as a treatment option.  Otherwise you have to attack the disease further down the line (better NMDA receptor antagonists, better antioxidants for instance). 

Posted: Saturday, March 16, 2019 12:02 PM
Joined: 2/26/2016
Posts: 263

There are three drugs available that affect leukotriene activity. Montelukast (brand name Singulair) and Zafirlukast (Accolate) block the actions of cysteinyl leukotrienes at its receptor on the surface of cells. Zileuton (Zyflo) works in a different way by interfering with the production of leukotrienes.


Zileuton may have been the best choice for research using mice, but it is not a good choice as a treatment for humans for long term use because it can produce serious side effects in some people. I have read that the Zafirlukast's brand name drug Accolate is no longer available, and the generic may be hard to find. Further there are some serious side effects in a small percentage of people. 


Montelukast is the drug I take and it very safe for long term use. I have been taking it for the past three years. The extreme mental fatigue and occasional confusion that I was experiencing completely disappeared shortly after I started taking this drug.


You can wait for the montelukast FDA clinical trial for Alzheimer's to be completed, hopefully late this year, but the only way for a person to know for sure if the drug works for him or herself is to try it. I am not a scientist and neither is Lane. I can only say from my experience that it works for me.