Combination Drug Stops Late Parkinson's Progression, Dyskinesia Effects

D-512 is an antioxidant combination drug that is the result of modified on-the-market receptor agonists.

An investigational compound drug has returned promising, long-term results for treating the progression of Parkinson's disease (PD).

The drug, known as D-512, is a modification of a competitor treatment’s molecules, said researcher Christopher Bishop (pictured), PhD, professor of psychology and behavioral neuroscience at Binghamton University.

It also has disease-modifying potential and antioxidant properties, which are significant for a potential PD medication, because excessive oxidative stress in a small group of movement-facilitating brain cells is what researchers currently understand to be at the root of the disease, Bishop said.

D-512 has shown particular promise in early animal model trials for its efficacy in late-stage disease progression — a phase during which most current agonist treatments begin to fade. At the same time, it did not exacerbate the chances of dyskinesia in animal models.

Some forms of the movement disorder dyskinesia are brought on by medications for conditions such as PD. The fact that D-512 did not increase dyskinesia risks while improving on current market drugs gives Bishop early hope for the drug.

“I wish we knew more about dyskinesia than we do, but one thing we found intriguing is the drug was very prominently anti-parkinsonian — I would cautiously say more so than ropinirol,” Bishop said. “The parkinsonian actions were prolonged, so we had that sort of superiority to it. And it wasn’t much different from current drugs in dyskinesia effects.”

Bishop noted the drug would potentially not carry the risk of dyskinesia development that common PD treatment levodopa carries when patients switch onto it in latter-progression stages.

Most of the initial drug development work was done in vitro, and the early phases of trial — seeded by the Michael J. Fox Foundation — need more research before D-512 can reach substantial levels of interest. The next line of work for Bishop and researchers lies in the drug’s foundations.

“We envision there’s 2 important steps we need to take,” Bishop said. “One is in the basic science of understanding how this drug is working. At the same time, because of the effects we see in vivo, we have to make sure it goes through all the safety testing.”

Still, the compound drug has caught Bishop’s interest, and leads to him vouching for further investigation into drug modifications.

“As we work with these compounds and structures, we’re continuing to build upon the treatments we already have,” Bishop said. “If we tweak the structure here or there, we may find an agonist that works even more.”

The study, "D-512, a novel dopamine D2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats," was published online in The British Journal of Pharmacology.

A press release regarding the study was made available.

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