Curative destruction: How Alzheimer’s disease can be defeated

The innovator: Dieter Willbold, Alzheimer’s revolutionary

Dieter Willbold Dieter Willbold (Photos: (c) Forschungszentrum Jülich / Ralf-Uwe Limbach)
Dieter Willbold is, among other things, a family man, an extremely early riser, a frequent commuter, a jogger, a biochemist, a biophysicist, an eminent authority on prions, an institute director and the founder of a spin-off.

More than anything else, he is the man who is revolutionizing Alzheimer’s research.


THE INNOVATION: THE CREATIVE DESTRUCTION OF TOXIC COMPOUNDS

Alzheimer’s disease. A plague that destroys brains, lives, people in its wake. The process of destruction follows a perfidious and unstoppable path: There are innocuous single proteins (monomers) that occur in the brain. These are the Abeta molecules. These can clump together and somehow manage to become toxic. Even worse: The toxic bundles (oligomers) reproduce at the expense of the monomers and cause the death of increasing numbers of neurons in the brain. Brain mass decreases, and little by little, the sufferer loses everything that once constituted his or her humanity.
Laboratory equipment

“If the toxic structures have been eliminated, this devastating disease can be stopped.”

Laboratory equipment
With scientific detachment and meticulousness, Dieter Willbold has been studying this horrifying process for a long time. On the one hand, he has done this as an expert on everything relating to the structure, function and dysfunction of proteins. Above all, however – and this is revolutionary – he brings a foundationally physical, equilibrium-oriented point of view to the task. This is how it became clear to him where the leverage for healing needs to be applied: The idea is to shift the balance between the ‘good’ single protein (the monomer) and the ‘evil’ toxic bundle (the oligomer). And according to Willbold, this is only possible if one introduces an active ingredient that can enter the brain efficiently, where it will then stabilize the monomer structure and split the oligomers into harmless monomers.

It is this virtually magical active ingredient that Dieter Willbold has developed – with his research spin-off, Priavoid. PRI-002 is what is known as an “All-D peptide” that can be produced at reasonable cost and easily administered orally (which means that it does not have to be injected intravenously, for example). “The active ingredient is important, but the disruptive innovation lies in the mode of action,” Willbold clarifies. “The breakthrough is the process itself, which breaks neurotoxic protein compounds down into harmless monomer building blocks.” And in the calm voice of a physical biologist, he adds: “If the toxic structures have been eliminated, this devastating disease can be stopped.”

Fortunately, Phase I clinical trials (on healthy subjects) focusing on safety and tolerability of the active ingredient have already been successfully completed. Together with SPRIND, Willbold now intends to develop the therapeutic agent further – with initially testing in Alzheimer’s patients as part of a Phase II clinical trial.

Since Dieter Willbold is far from a fan of anything unrealistic, we can state his prediction in appropriately understated terms: There is a scientifically well-founded hope that Alzheimer’s dementia can be defeated. And the name of that hope is “PRI-002.”
CONTEXT:
Dieter Willbold is Professor of Physical Biology at Heinrich Heine University Düsseldorf and Director of the Institute of Structural Biochemistry at Forschungszentrum Jülich. Of course, he does not conduct research alone. He is part of a network of highly competent colleagues and friends in the scientific community. Biophysicist and prion investigator Detlev Riesner encouraged him to establish his company Priavoid: “Willbold, this is a great idea. Now you have to get a move on and create a spin-off.” Riesner is the co-founder of several biotech companies, among them the diagnostics company Qiagen. He has also long been friends with Stanley Prusiner, the recipient of the 1997 Nobel Prize in Physiology or Medicine – for his discovery that there are pathogens that consist neither of RNA nor of DNA but of proteins. He dubbed these proteins “prions.”
The anti-prionic mode of action of PRI-002 inspired Dieter Willbold to call his spin-off “Priavoid.” Prusiner himself is so convinced of the groundbreaking developments around PRI-002 that – together with Detlev Riesner and Dieter Willbold – he will serve on the Supervisory Board of Priavoid in the effort to advance this research even further.