Parkinson’s disease research at Johns Hopkins is largely housed in the Institute for Cell Engineering. For more than two decades, investigators Ted and Valina Dawson have been diving deep into Parkinson’s disease—how it develops, what proteins are involved, and what potential drugs could be developed to halt its path. Their laboratory at the Johns Hopkins University School of Medicine, in Baltimore has yielded a number of significant discoveries uncovering the disease process. Now, they’re on the forefront of moving forward, developing some of the first experimental drugs with the potential to stop the degenerative disease in its tracks.
Current Areas of Focus
The Dawson’s research group has two investigative drugs that are entering clinical trials, called NLY01 and c-Abl inhibitors. NLY01 works by binding to a chemical receptor called glucagon-like peptide-1 on the surface of certain cells. This blocks brain cells from degrading. The drug is being offered through a biotechnology company called Neuraly that was formed by the Dawsons and colleagues Han Seok Ko and Seulki Lee.
The Dawsons also are involved in testing of agents that inhibit c-Abl, a protein involved in the development of Parkinson’s disease. In addition, their labs are working on developing drugs to inhibit additional proteins involved in the development of Parkinson’s disease, such as parkin, PARIS, MIF, PARP and LAG3.
Beyond drug therapies, the Dawsons are working on laboratory tests to detect the presence of Parkinson’s disease in cerebrospinal fluid, and imaging tools to study inflammation in the brain. These could be used in combination with new clinical treatments to assess how well they work.
About Parkinson’s Disease
Parkinson’s disease is the second most common neurodegenerative disease in the world, after Alzheimer’s disease. It is estimated that there are over 6 million people worldwide who suffer from the condition, which has no treatment and no cure.
Parkinson’s disease affects people of both genders and all nationalities and ethnic backgrounds. Although most people begin showing symptoms in their 60s, cases have been reported in patients as young as 2 years old.
Many people think of the condition as a movement disorder because of tremors and shaking seen in the hands and limbs. But these symptoms appear at the end stage of disease. Parkinson’s actually starts much earlier. It first impacts reflexes in the gut that normally move waste through the intestines, causing constipation. As the disease progresses, it involves the autonomic nervous system, causing variability in heart rate and other issues. Then, as Parkinson’s moves into the brain, it causes motor symptoms like tremor and loss of balance, as well as non-motor symptoms such as sleep disorders, anxiety, depression and dementia. It is estimated that 80% of Parkinson’s patients have anywhere from mild cognitive impairment to mild dementia. Thirty percent, by the time they die, have full dementia and require 24-hour care for daily tasks of living.
Current treatments for Parkinson’s disease address only the symptoms of the disease to make day-to-day life more manageable, but do nothing to halt the disease’s progression.
How Parkinson’s Develops
The human brain consists of billions of neurons, or nerve cells, that exchange tiny molecules to send messages throughout the body. The movement of these molecules from one place to the next is essential to who we are: They allow us to walk and talk, construct our memories and inform our consciousness. They can also cause disease when things go wrong.
One of these molecules is called alpha synuclein. In Parkinson’s disease, alpha synuclein begins to misfold and form curve-shaped fibers that clump together. The clumps plug up the neurons or kick off a biochemical cascade of activity leading to dysfunction of the mitochondria (the powerhouses of cells) and cell death. As more and more neurons are lost, the brain develops “dead zones”— like a forest after a wild fire - where vital brain tissue has been lost.
Scientists do not yet know why these proteins clump together. More than 90 percent of patients have no apparent family history of the disorder.