Previously experts from the Medical Research Council and Imperial College London shared that transplant treatment may increase symptoms of Parkinson’s disease. Now, researchers from Johns Hopkins revealed that specific drugs may have the ability to shield nerve cells in mice from lethal effects of Parkinson’s disease.
The latest drug restricts a protein that, when modified in people may lead to Parkinson’s disease. The disease causes worsening of the nervous system which apparently leads to tremors and problems with muscle movement and coordination. However, there is no proven treatment yet and genetic causes of the disease have recently been identified. This may help in developing therapies for patients with the disease.
The protein LRRK2 is seemingly overactive among some Parkinson’s disease patients and it may stimulate the nerve, wither and eventually die. There is limited knowledge as to why overactive LRRK2 is toxic and leads to Parkinson’s disease.
“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,” remarked Ted Dawson, M.D., Ph.D., professor of neurology and physiology and scientific director of the Johns Hopkins Institute for Cell Engineering.
As overactive LRRK2 is harmful, experts share that restricting LRRK2 from acting may safeguard nerve cells. The team evaluated drugs that were commercially available and known to avoid proteins like LRRK2 from acting and adding chemical phosphates to other proteins. Eight drugs were found to block LRRK2 from working from 70 drugs tested.
Two of these eight initially were shown to surpass the blood-brain barrier. Therefore they were injected twice daily into mice engineered to carry Parkinson-causing LRRK2 changes in their brain. Experts observed the mouse brains after three weeks to identify if nerve cells had deteriorated.
Researchers were surprised to identify that one drug offered utmost protection against nerve cell death, while another drug had about 80 percent fewer dead cells. They also shared that a third drug which does not reduce LRRK2 was seemingly ineffective. The two drugs that restricted 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,” Dawson added.
Researchers plan to develop more inhibitors of LRRK2 and they plan to license this technology. Once they identify promising candidate drugs they will have to be further tested for toxic side effects. They share that the drugs’ approval by the FDA for use in humans may still be many years away.
“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 remarked.
Dawson highlights that treatments developed specifically against LRRK2 may even be able to treat other forms of Parkinson’s disease. It should not be caused by LRRK2 alterations as there may be changes in several proteins that can lead Parkinson’s disease.
These findings were published in the August 22 issue of Nature Medicine.