Perspectives – Prof. Martin Keller
A Carefully Planned Accident
Co-Creation – Dr. Janine Kutzsche
They were looking for a treatment for Alzheimer’s disease. What researchers found was not only a promising treatment for Alzheimer’s, but a compound that could one day help close the microscopic gates behind neuropathic pain.
June 2026
A chronic pain
A breeze that feels like sandpaper. A bedsheet that becomes torture. For millions of people living with neuropathic pain, this is everyday life. Their bodies may show no obvious injury, yet the pain remains - an echo of disease after chemotherapy, diabetes or multiple sclerosis. Nerve cells keep firing pain signals for no good reason and without end. It is like a fire alarm still ringing in a house where the fire has long been put out.
At the centre of this false alarm are tiny gates inside nerve cells: N-type calcium channels. They are found especially in the spinal cord, which together with the brain forms the central nervous system. These channels act as relay points, passing pain signals between nerve cells. In a healthy system, a calcium channel opens briefly, letting a signal pass in a controlled way. In chronic pain, the door jams wide open. Calcium ions stream into the nerve cells, and the cells keep sending alarm signals to the brain.
Closing that stuck door - and silencing the alarm - is difficult. People with neuropathic pain are often non-responders: standard drugs do little or nothing for them. "Even strong painkillers such as opioids often reach their limits in neuropathic pain and also carry a high risk of addiction. The cause is not in the tissue itself, but in the body’s signalling centre," says Dr Janine Kutzsche. The biologist at the Institute of Biological Information Processing - Structural Biochemistry studies neurodegenerative and neurological diseases.
Still, Kutzsche and her team have found a possible way to intervene in the jammed mechanism. The curious part is that they were not looking for it.
Crossing the Security Gate
The team had originally been working on a different disease: Alzheimer’s. They were investigating promising compounds known as D-peptides. These molecules exploit a physical loophole. Almost all naturally occurring peptides - basic building blocks of life - are "left-handed" in their molecular geometry. The body is tuned to this shape. Enzymes recognise such peptides and break them down within seconds.
The D-peptides developed in Jülich are mirror-image versions of natural peptides. That gives them a major advantage: the body degrades them much more slowly, so they remain stable for longer. Some of these specially designed compounds can also cross the blood-brain barrier and act directly in the brain. "This barrier is like a biological high-security gate," Kutzsche says. "It protects our brain very effectively - but it also keeps out many potentially useful drugs."
„We carry a great responsibility. We are working on solutions for people who have suffered for years. That creates hope - and precisely because of that, we have to be especially careful.“
— Dr. Janine Kutzsche
A Serendipitous Target
The Jülich researchers developed one particular D-peptide as a potential Alzheimer’s treatment. It is called RD2. On its path towards approval, RD2 has already cleared an important first hurdle: in a Phase I clinical trial, researchers showed that the D-peptide is safe and well tolerated. Clinical development also means looking for so-called off-targets - unintended sites of action that might cause side effects.
With RD2, Kutzsche and her colleagues discovered something nobody had expected: the peptide docked precisely onto the N-type calcium channel. "The discovery was accidental, but once we saw the direct effect on the channels, we realised that our compound might also help against neuropathic pain," the Jülich researcher recalls.
Until now, some patients have had only one last-resort option: ziconotide. This peptide cannot cross the blood-brain barrier and would be broken down in the digestive tract if taken as a tablet. Doctors therefore have to inject it directly into the spinal fluid - an invasive procedure close to the spinal cord, where the relevant calcium channels are located. Ziconotide can relieve neuropathic pain effectively, but it often causes severe side effects.
The Jülich peptide could be different. Patients might be able to take it orally. Thanks to its mirror-image structure, it remains more stable in the body, breaks down more slowly and finds its own way to the calcium channel, where it docks and gently closes the jammed door.
Warning Signal on Repeat
In neuropathic pain, damaged nerves keep sending alarm signals to the brain. Inside the cells, microscopic gates - the N-type calcium channels - become stuck. In a healthy system, they open only briefly. In neuropathic pain, they remain wide open.
Calcium ions flow through unchecked, making even a light breeze feel like sandpaper on the skin.
Still a Long Way to Go
Because RD2’s effect on neuropathic pain began as a chance finding, the researchers are now optimising the compound further without losing its specificity. "Calcium channels also exist elsewhere in the body. Our compound should block only the calcium channels in pain-transmitting nerves, while leaving channels in the heart and other organs untouched," Kutzsche stresses.
The team benefits from the head start created by the successful Phase I trial in healthy volunteers during the Alzheimer’s programme. In initial animal-model studies, the researchers have also shown that RD2 can suppress pain signals and reduce typical symptoms such as hypersensitivity.
Pain Without Restraint
N-type calcium channels are located in the spinal cord, part of the central nervous system. They act as relay points for pain signals passing between nerve cells.
Investors have already taken notice. Kutzsche does not rule out the possibility that the compound could one day become the basis for a spin-off. Even so, she remains cautious. "We carry a great responsibility. We are working on solutions for people who have suffered for years. That creates hope - and precisely because of that, we have to be especially careful." No one can say with certainty whether the work will ultimately lead to an approved drug. The pressure is high, funding is often tight, and regulatory demands grow with every new phase of clinical testing.
At least Kutzsche and her team may be spared one challenge familiar from Alzheimer’s research: years of complex cognitive tests. The success of their compound against neuropathic pain could be measured by one simple question to patients: "Do you still feel pain?" If the answer is no, that would be the moment when a cotton T-shirt could become, once again, what it should be for people with neuropathic pain: a matter of fashion.
Discover the research group led by Janine Kutzsche
Image credit: Forschungszentrum Jülich
Perspectives: The new Issue
Some diagnoses change the way we view our own lives, often leading to a long road, full of uncertainty and unanswered questions.
In this issue, we meet researchers who are developing new approaches to treating cancer, chronic pain and other diseases. Their work is producing insights that could one day change how we view these diagnoses.
Read more
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Last Modified: 09.07.2026