July 22, 2015

News from the Alzheimer’s Conference in DC: A New Plaque-Busting Drug for Alzheimer’s and Parkinson’s?

There have been several interesting announcements at the Alzheimer’s Association International Conference (AAIC) taking place here in Washington, DC this week.
  • Alzheimer’s disease (AD) advances twice as fast in women than it does in men. That’s especially important since about two thirds of all Americans with AD are women. In fact, that speed of development may partly explain the gender imbalance.
  • A simple saliva test could identify AD much sooner. That’s important because earlier diagnoses are key to treating this disease, which inflicts so much irreversible damage for many years before it is even identified.
  • A new drug under development targets and removes various disease-causing plaques in the brain. The source of that new drug? A virus found in sewage. Sounds a bit like Alexander Fleming’s unlikely and serendipitous discovery of penicillin nearly a century ago.
This promising new plaque-busting drug is the focus of today’s post.

Plaque Attack
When proteins misfold in the brain, they eventually form plaques, which become the accumulating clumps of gunk responsible for several different neurological diseases, including AD, PD, and Creutzfeldt-Jakob disease.

The new drug – NPT088 for now – has already proved successful in breaking up plaques in mice affected with AD or PD. Memory and cognitive improvements in those animals were dramatic enough that developer NeuroPhage Pharmaceuticals intends to apply soon for permission to begin clinical trials on people, which could start in 2016.

What’s really different about NPT088? It seems to attack and destroy a variety of different plaque types linked to human neurological diseases… and not just the individual proteins that build up to create the plaques which eventually disable normal brain function. So far, potential therapies have targeted proteins as bio-markers, not plaques.

I’ve written often on this blog about the different plaques associated with the two diseases most on my mind: the Parkinson’s I have and the Alzheimer’s I fear. The graphic here – “Proteins Gone Rogue” -- shows which misfolded proteins are responsible for creating the plaques associated with the most common neurological diseases.

Those plaques are different and unique. But they share something in common: structural kinks known as “canonical amyloid folds.” It is precisely those folds that the new drug attacks.

Proteins that are folded correctly – the proteins that make bodies function properly – do not have that canonical amyloid folds, and are thus completely unaffected by the drug.

Maria Carrillo, chief science officer at the U.S. Alzheimer’s Association, spoke about NPT088: "This is a next-generation drug. It could be stopping the root causes of these diseases and preventing them happening."

The Usual Caveats
As always, there are cautions:
  • Progress in treatments for neurological diseases has been slow, and there have been many “false dawns.”
  • The clinical trial leap from mice to men is enormous.
  • Medical authorities want to see more results.
  • Experts correctly ask if reducing brain plaques with this drug will actually halt or slow down neural deterioration.
There is some reason for hope. Aducanumab, the only drug now available that targets plaques (not just proteins) is also the only drug to date that has shown signs of halting the progress of AD.

At this week’s conference, NeuroPhage chief scientist Richard Fisher explained his excitement about NPT088’s therapeutic potential for AD: it targets both of the plaques that accumulate from various protein types. He said, “This is something very novel. There’s never been anything that can target all these plaques simultaneously.”

Human clinical trials could begin in 2016. Will NPT088 prove to be a revolutionary new therapy for AD and PD… or just another “false dawn” in the ongoing quest?

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