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A new substance that inhibits Parkinson’s disease in mice brings researchers one step closer to developing a new drug to fight the disease. Pharmaceutical researchers at Utrecht ľ�ϸ���Ӱ�� have tested the medication, which is produced by a Dutch pharmaceutical firm. They have published their joint findings in the scientific periodical FEBS Journal.

Parkinson’s disease is what is known as a ‘neurodegenerative illness’. It is characterised by the accumulation of toxic waste substances in the brain, which cause neurons to deteriorate. This results in many different problems. Parkinson’s patients suffer from stiff muscles and uncontrolled, uncoordinated movements. Other symptoms include depression and cognitive decline. More than 50,000 people suffer from the disease in the Netherlands alone.

We expect that the drug will also work with related diseases, such as Alzheimer’s and Huntington’s disease.

Utrecht ľ�ϸ���Ӱ�� pharmaceutical researcher Aletta Kraneveld emphasises the urgency of finding a new medication for the condition: “At the moment, there are only a limited number of drugs to treat Parkinson’s, and those therapies only help improve muscle activity. But they have so many side effects that you can’t use them forever.”

Inhibiting excessive enzyme activity

The toxic substances that cause Parkinson’s are created by the excessive conversion of the amino acid tryptophan.  Kraneveld: “In a disease like Parkinson’s, the conversion of tryptophan along a specific breakdown route, called the kynurenine route, is disrupted. It begins with the enzyme tryptophan-dioxygenase, or TDO for short. In Parkinson’s disease, the conversion of tryptophan goes off the rails, as it were. But now, the researchers at the pharmaceutical company NTRC in Oss have developed a substance that inhibits the creation of the toxic waste products. We’ve tested the TDO inhibitor in our lab in Utrecht, and it actually works.”

NTRC researcher and Director Guido Zaman: “The effect of the drug is generally thought to be very innovative. Considering the similarities between Parkinson’s disease, Alzheimer’s and Huntington’s disease, we expect that the TDO inhibitor might also work for those diseases as well.”

In Parkinson’s disease, the conversion of tryptophan goes off the rails. The TDO inhibitor apparently reduces the creation of toxic waste substances.

Fewer intestinal problems

Scientists have long known that Parkinson’s disease is also expressed in the nerve cells in the intestines. Kraneveld: “So Parkinson’s is also often accompanied by abdominal pain and constipation. In many patients, these symptoms actually occur earlier than the stiffness and uncontrolled movements. In mice, we’ve observed that the new TDO inhibitor also reduces the intestinal problems by inhibiting the inflammation reaction in the intestines and improving intestinal function.”

High bar for new medications

Over the next few years, NTRC will continue to optimise the TDO inhibitor it has developed. Zaman: “The bar for bringing new medications to market is of course very high. We have to test the substance in a second animal model, and if that produces positive results then we can test how the inhibitor works in humans.” For a relatively small pharmaceutical company like NTRC, fundraising is crucial. “In the first phase, we received support from the Michael J. Fox Foundation and NWO. We hope that we’ll be able to find funding for the next step as well.”

The pharmaceutical researchers at UU are eager to test the improved medications. Kraneveld: “And we also have several research questions. For example, we’re curious how the drug works at the molecular level in the brain. We’d like to do some more follow-up research on that.”