Research Targets Protection of Nerve Cells in Parkinson’s
Scientists at John Hopkins have demonstrated on mice that certain drugs protect nerve cells from the deadly effects of Parkinson’s disease. These findings can be found in the August 22 issue of Nature Medicine.
Parkinson’s disease promotes deterioration of the nervous system resulting in tremors and problems with muscle coordination and movement. As of yet, there is no proven protective treatment. Only recently have genetic causes of Parkinson’s disease been identified with the potential for being used in developing targeted treatments.
Recently discovered drugs, however, have been found to block the protein LRRK2 (pronounced lark 2), which, when distorted in humans, leads to Parkinson’s disease by causing nerve cells to shrivel up and die.
Since overactive LRRK2 is deadly, researchers speculated that by putting a block on LRRK2, they could protect the vulnerable nerve cells this protein attacks. The scientists tested drugs that were commercially available and known to prevent proteins like LRRK2 from acting and adding chemical phosphates to other proteins. Seventy drugs were tested in all, and eight were found to block LRRK2 from acting.
Out of the eight drugs, two had been previously shown during other studies to be capable of crossing the blood-brain barrier. So the scientists injected these two drugs twice daily into mice engineered to carry Parkinson-causing LRRK2 changes in their brain. After three weeks, the researchers observed the mouse brains to identify if any nerve cells had died. One drug provided almost total protection against nerve cell death. Another drug had approximately 80 percent fewer dead cells than in mock-treated mice. A third drug, which does not inhibit LRRK2, was proven not effective.
“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 Ted Dawson, M.D., Ph.D., scientific director of the Johns Hopkins Institute for Cell Engineering and professor of neurology and physiology.
The two drugs successful in blocking LRRK2 and preventing nerve cell death in mice with Parkinson’s disease were made of similar chemical structures. “One could envision generating compounds around that core structure to develop a relatively selective and potent inhibitor of LRRK2,” Dawson says.
Dawson, in collaboration with researchers at Southern Methodist University, is designing specific inhibitors of LRRK2 with plans to license the technology. Once the candidate drugs are identified, they will be tested for toxic side effects. It still may be years, however, before the drugs are approved by the FDA for use in humans.
According to Dawson, treatments developed specifically against LRRK2 may even be able to treat other forms of Parkinson’s disease — those not caused by LRRK2 alterations — as there may be various alterations in different proteins that can lead to Parkinson’s disease.
“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,” Dawson says.
Other authors on the manuscript included Byoung Lee, Joo-Ho Shin, Andrew West, HanSeok Ko, Yun-Il Lee and co-investigator Valina Dawson of Johns Hopkins Medicine; Jackalina VanKampen and Leonard Petrucelli of the Mayo Clinic College of Medicine; Kathleen Maguire-Zeiss and Howard Federoff of the Georgetown University Medical Center; and William Bowers of the University of Rochester Medical Center.
Funding for this research was provided by grants from the National Institutes of Health, the Army Medical Research and Material Command, the Mayo Foundation and the Michael J. Fox Foundation.
Pedersen, T. (2018). Research Targets Protection of Nerve Cells in Parkinson’s. Psych Central. Retrieved on September 29, 2020, from https://psychcentral.com/news/2010/09/01/research-targets-protection-of-nerve-cells-in-parkinsons/17524.html