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The federal Food and Drug Administration has approved a new Parkinson’s disease drug that was based on research by UVA Health scientists. 

The drug tavapadon, now branded Juvmo, was pioneered by UVA School of Medicine Professor of Pharmacology and Neuroscience Richard B. Mailman, PhD. UVA Health’s Xuemei Huang, MD, PhD, Chair, Department of Neurology, also played a vital role in the first successful clinical trial with a drug of this class. 

Early drugs in the class, called D1 agonists, could only be injected, but Juvmo is taken as a pill once per day. The current gold-standard Parkinson’s medication, levodopa, requires multiple doses per day at increasingly frequent intervals as the disease progresses.

“The gold standard drug for nearly 60 years has been levodopa, available in many forms. Unfortunately, it requires some of the very nerve cells that are dying in Parkinson’s. This means it is harder to use and less effective with time,” Mailman says. “We figured out the specific mechanism that made levodopa effective, and developed the first drug that could turn on that mechanism. Juvmo itself was made by a brilliant chemist and team who made a similar drug that could be given as a pill only once or twice a day.” 

More than 11 million people around the world live with Parkinson’s, one of the fastest-growing age-related neurological conditions. Parkinson’s causes tremor — shaking — as well as stiffness, slowness, and difficulty moving. It increases the risk of falls and can come with symptoms such as fatigue, insomnia, memory loss, and impaired ability to concentrate. 

The disease is driven by the gradual death of nerve cells that make and use the hormone dopamine. Despite decades of research, no way has been found to stop this degeneration. Juvmo, however, can selectively activate D1 dopamine receptors in the brain, providing relief from some of the disease’s motor symptoms.

The drug’s unique way of working means it may cause fewer side effects than levodopa, its developers say. While Juvmo can be combined with levodopa, Juvmo also may serve as an important new option for patients for whom the symptoms cannot be optimally controlled. 

About 70% of patients taking levodopa need to have their dose increased within the first year. But 93% of clinical trial participants receiving Juvmo had not increased their dose of levodopa after 85 weeks, while 94% with early Parkinson's had not needed to start levodopa.

“Because the target of Juvmo does not degenerate in Parkinson’s disease, the hope is that it will smooth out current problems and also allow symptomatic relief to continue for much longer periods," Dr. Huang says. “Indeed, our own research has suggested that there is hope that it might be helpful for patients in very late stages of PD for whom we do not have effective therapy. With the availability of Juvmo, these ideas can be tested.”

Mailman has spent decades on the research that led to Juvmo. His big breakthrough came in 1984, when he realized all the existing “dopamine agonists” targeted a specific subset of receptors called “D2-like.” His experiments suggested the other type of dopamine receptor (“D1-like”) actually was responsible for most of levodopa’s beneficial effects. He also suspected targeting D1-like receptors would not have many of the side effects of the approved dopamine-agonist drugs. 

Dr. Huang joined the research team in the late 1990s, designing a clinical study that showed that D1 agonists could be administered in a way that avoided blood pressure problems that had plagued previous attempts.

As he continued his research, Mailman went on an odyssey to convince pharmaceutical companies, large and small, of the promise of his approach. He persisted despite an overall feeling within the industry that the Parkinson’s market was too small to be worth the investment. A key breakthrough was finding a team at Pfizer led by David L. Gray, PhD, who was convinced by Mailman’s data. Their efforts led to the success of Juvmo. 

Juvmo will be marketed by the drug company AbbVie and is expected to become available in October. 

Mailman is delighted to see his ideas finally able to benefit patients. “It has been frustrating to think that we had a breakthrough for Parkinson’s patients and could not get others to see this vision. A key early collaborator for his work was Professor Steven Wyrick, who was diagnosed with Parkinson’s but never lived to try a drug in which he believed,” Mailman says. “It would have made the long journey worthwhile if this helps begin a new era of Parkinson’s treatment.”

Mailman and Dr. Huang continue to research other possible applications for tavapadon and other D1 drugs beyond the scope now approved by the FDA.

Finding better ways to treat complex diseases is a major mission of the new UVA Paul and Diane Manning Institute of Biotechnology — which aims to more quickly translate UVA’s cutting-edge science into new drugs and treatments to benefit patients across Virginia and beyond.