A promising target for developing treatments against Parkinson’s


Researchers at Johns Hopkins have shown that using specific drugs can protect nerve cells in mice from the lethal effects of Parkinson’s disease. The newly discovered drugs block a protein that, when altered in people, leads to Parkinson’s disease.

Parkinson’s disease causes deterioration of the nervous system that leads to tremors and problems with muscle movement and coordination. There is no proven protective treatment yet, due to unknown factors of the disease, such as the role of the protein LRRK2 (pronounced lark two), which is overactive in some Parkinson’s disease patients and causes nerve cells to shrivel up and die. Why exactly overactive LRRK2 is toxic and leads to Parkinson’s disease is still unknown.


Researchers speculated that blocking LRRK2 from acting might protect nerve cells, testing commercially available drugs known to prevent proteins like LRRK2 from acting and adding chemical phosphates to other proteins. Out of 70 drugs tested, eight were found to block LRRK2 from working. Two of these eight previously were shown by others to be able to cross the blood-brain barrier. So the researchers injected these two drugs twice daily into mice engineered to carry Parkinson-causing LRRK2 changes in their brain. One drug provided almost complete protection against nerve cell death after three weeks, with the other losing approximately 80% fewer cells than in mock treated mice.


“This data suggests that if you were to develop a safe drug, then you could potentially have a new treatment for Parkinson’s disease patients with LRRK2 mutations,” says Dr Ted Dawson, professor of neurology and physiology and scientific director of the Johns Hopkins Institute for Cell Engineering. The two drugs that blocked LRRK2 and prevented death of nerve cells in mice with Parkinson’s disease both had similar chemical structures. “One could envision generating compounds around that core structure to develop a relatively selective and potent inhibitor of LRRK2,” says Dawson.


Dawson is collaborating with researchers at Southern Methodist University to design more specific inhibitors of LRRK2 and the group plans to license this technology. But even when they identify promising candidate drugs, those candidates still will have to be tested for toxic side effects, so drugs’ approval by the FDA for use in humans may still be many years away. But he remains positive that the changes seen in mice will be transferrable to human patients.


“We’re curing Parkinson’s disease in a mouse and now we have to discover drugs that actually work in human neurons. Then we’ll hopefully be able to make the leap forward to get a treatment to work in humans,” says Dawson.


The researchers’ findings are published in the August 22 issue of Nature Medicine.