For 50 years, levodopa and similar pharmaceutical drugs have been quintessential in treating Parkinson’s disease.
These medications ease the motor symptoms of the disease, though none can cure the illness for good.
Over time, people with Parkinson’s continuously lose dopamine neurons, cells that’re necessary to the motor control centers of the human brain. Medications like levodopa will eventually become ineffective. As a result, the body loses its sense of balance, and a debilitating stiffness dominates the legs.
To prevent this slow, deterioration of the body’s motor functions, scientists are vigorously working to replace those critical dopamine neurons.
Through much trial and error, stem cell therapy is next to experiment with as a potential answer to replenishing dopamine neurons or, as a cure for Parkinson’s altogether.
A MAJOR BREAKTHROUGH
A study from the Karolinska Institute in Stockholm, Sweden, is giving hope to stem cell researchers and Parkinson’s patients alike.
Their researchers successfully proved it’s possible to entice the brain’s own astrocytes which are cells that support and nurture neurons to produce new dopamine neurons.
The reprogrammed cells share several properties and functions of organic dopamine neurons, meaning they can play a part in preventing the debilitating effects of Parkinson’s, says the researchers.
“You can directly reprogram a cell that is already inside the brain and change the function in such a way that you can improve neurological symptoms,” said Ernest Arenas, senior author of the study, and a professor of Medical Biochemistry at Karolinska.
In the past, specialized cells like neurons had to become pluripotent cells before they could develop into a different kind of specialized cell.
Think of it as erasing all the written instructions on how a cell should develop, and what its job is, and then rewriting everything all over again.
With Arenas and his team’s breakthrough, they’ve ‘edited’ the instructions into a new list of directives, rather than wiping the slate clean.
To force astrocytes into transforming directly into dopamine neurons, they combined a mixture of three genes and a tiny RNA molecule. The human astrocytes created with this technique acted just like normal, midbrain dopamine neurons; the new cells grew axons, which are the long fibers that connect to other neurons, firing off electrical signals and releasing dopamine.
In order to test the functionality of the manufactured dopamine neurons, the researchers used any clinical trial’s best friend: mice. The scientists destroyed the dopamine neurons in one part of the mice’s brains, producing the model of Parkinson’s. Then, they injected their stem cell cocktail of genes into the brain, observing the mice as they walked on mini treadmills.
After just five weeks, the mice were walking straighter, their movements were more coordinated, and their posture was better.
A CURE FOR PARKINSON’S?
With the success of the trial, Arenas’ findings could open the door for a novel therapeutic approach to Parkinson’s.
Converting astrocytes directly or ones that’re already present in a patient’s brain eradicates the need for donor cells. The risk of immunosuppression of transplanted cells would be solved, too. Plus, the gene cocktail would produce proteins needed in normal cellular processes, making it less likely to create problematic side effects, like other medications can.
“This is like stem cell 2.0. It’s the next-generation approach to stem cell treatments and regenerative medicine,” says James Beck, vice president and chief scientific officer for the nonprofit Parkinson’s Disease Foundation (they weren’t involved in the study).
Supplanting lost dopamine neurons with reprogrammed cells would make managing motor symptoms much, much easier. And rather than the inconvenience of taking eight pills every day for people in the late stages of the disease, the medications would shrink possibly to zero.
But that’s not to say there aren’t a few bumps that need to be paved first. While the stem cell treatment may help with motor symptoms initially, it won’t stop the course of Parkinson’s. And losing more and more neurons as the disease progresses could mean additional reprogramming procedures of replacement cells.
Parkinson’s isn’t only defined by motor symptoms, but a bunch of nonmotor symptoms as well cognitive impairment, depression, gastrointestinal complications, and autonomic dysfunction, to name a few.
In other words, improving motor symptoms is just half the battle.
Stem cell researchers will still need to confirm their cocktails of genes are standardized, and manufacture robust cells in future trials. They must also be mindful of the process and its effect on other cells: having the cocktail change other cells in the brain could be fatal.
But if this direct-reprogramming technique is refined, don’t be surprised if it usurps stem cell therapy in the next decade.
“This is an insight into what the future of Parkinson’s treatment holds,” says Arenas.
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