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Posted: Sunday, October 6, 2019 9:25 AM
Joined: 7/10/2017
Posts: 663

Clinical trials test new approach to tackling Alzheimer's  


A fresh approach to tackling Alzheimer's disease is being investigated in an innovative clinical trial in Australia. The study is taking a closer look at the role of chronic inflammation in Alzheimer's, moving beyond the historical focus on brain plaques and tangles. The trial is funded through a $1 million grant from the Alzheimer's Association Part the Cloud program, which funds research on new approaches to Alzheimer's therapy

  Link is to:



Hmmm.  Lane, any comments?


Lane Simonian
Posted: Sunday, October 6, 2019 11:09 AM
Joined: 12/12/2011
Posts: 5107

Thanks very much for posting information about this drug, Mike.

XPro1595 reduces inflammation by inhibiting Tumor necrosis factor-alpha which is a major player in inflammation.  Inhibiting TNF-alpha appears to significantly reduce the risk for Alzheimer's disease in those with inflammatory related diseases.

Systemic inflammatory diseases involving tumor necrosis factor (TNF) increased the risk of Alzheimer's disease, but that risk was reduced in patients who used anti-TNF biologics, an analysis of 56 million adults' electronic health records showed.

The potential problem with TNF-alpha inhibitors is that they increase the chances of other diseases because of a surpressed immune system.  XPro1595 claims to dampen the negative effects of immune responses (neuroinflammation) while maintaining positive immune responses (getting rid of cellular debris).

Whether it actually does so remains to be seen.

Of the neuroinflammation approaches to Alzheimer's disease, this is probably the best one.  Some companies are targeting proteins (such as Cox-2 enzymes and leukotrienes) and activated microglia downstream from tumor necrosis factor-alpha, but part of the damage done by oxidation and nitration has already occurred at this point.  Tumor necrosis factor-alpha contributes to nitro-oxidative damage in Alzheimer's disease and to neuroinflammation (which then leads to more peroxynitrite formation).

Once neuroinflammation is recognized as a secondary factor in Alzheimer's disease rather than a primary one, more progress against the disease should be made.  Inhibiting neuroinflammation may slow down the progression of the disease, but it does not address the damage that has already been done to the brain via oxidation and nitration.  Compounds (various herbs such as ginseng, medicinal marijuana, various essential oils via aromatherapy) that do the latter seem to be more effective treatments for Alzheimer's disease.

My heart is heavy thinking about all those caring for a loved one with Alzheimer's disease and other forms of dementia.  Brenda and you are in my thoughts.


Posted: Monday, October 7, 2019 10:50 AM
Joined: 2/26/2016
Posts: 263

The upside of this drug is that it targets only one of the two forms TNF (soluble TNF) and is safer than previous TNF inhibitors. TNF is one of the many types of immune signaling molecules (cytokines) found in the immune system. Much research in Alzheimers is now focused on developing drugs to target the brain's immune system, and this drug has shown a lot of promise.

There are also some downsides to this drug. Determining if it is safe and effective will take many years, making for a long wait before it becomes available to patients. It is a drug that can only be taken by IV or injection. Further it is a biologic that will be very expensive, simular to biologic cancer drugs that cost hundreds of thousands of dollars a year. Maybe the federal government will crack down on the outrageous cost of these new drugs by then, but I doubt it.

This drug may be effective but the question may be how effective. No doubt there are other cytokines besides TNF that are also envolved in Alzheimers and dementia. For example the drug montelukast blocks the cytokines LTC4, LTD4, and LTE4, which are all leukotrienes. And it is available now and is safe and very cheap. Some clear results on montelukast in Alzheimer clinical trials should come by late next year.

There are so many biologic cancer drugs that have been approved by the FDA that promise a lot and deliver very little at a very high price. I hope this TNF blocking drug will do better.

Lane Simonian
Posted: Monday, October 7, 2019 2:00 PM
Joined: 12/12/2011
Posts: 5107

Well-reasoned and well-said, Larry.  I have my doubts inhibiting any one receptor or group of receptors involved in neuroinflammation is enough to radically change the course of Alzheimer's disease, but I would be pleased to be wrong.  Any movement away from the amyloid/tau focus for the treatment of Alzheimer's disease is progress.