'Personalized' grafts reverse Parkinson's in monkeys
10 March, 2021
The primary symptoms of Parkinson’s disease are tremor, stiffness, slowness of movement, and impaired balance and coordination.
The disease may also cause difficulty swallowing, chewing, and speaking. Furthermore, people may experience emotional changes, such as for example depression.
Damage to dopamine-producing nerve cells situated in the midbrain is accountable for the majority of the symptoms of Parkinson’s disease.
Treatment with drugs such as for example L-Dopa can alleviate the symptoms by replenishing the brain’s supplies of dopamine, however the drugs do not prevent the progressive degeneration of dopamine neurons.
“Those drugs work very well for many patients, however the effect will not last,” says Prof. Marina Emborg, who researches Parkinson’s at the Wisconsin National Primate Research Center, area of the University of Wisconsin-Madison (UW-Madison).
“Eventually, as the condition progresses and their motor symptoms worsen, they are back to devoid of enough dopamine, and side effects of the drugs appear,” she explains.
For more than 4 decades, researchers have already been tinkering with transplants of fetal tissue as cure for Parkinson’s, first in animal types of the condition and later in people.
However, the results have been mixed, in part since the disease fighting capability recognizes the tissue as foreign and attacks it. As a result, recipients need to take immunosuppressant drugs.
Another problem with this approach is that fetal tissue is difficult to obtain in large quantities and varies in its composition and quality.
Universal stem cells
A promising alternative is dopamine cells produced from induced pluripotent stem cells (iPSCs), which are cells which can be transformed into nearly every type of cell in the body.
Researchers create iPSCs by “rewinding” the developmental clock of a person’s own skin or blood cells. Crucially, this signifies that the immune system will not attack cells descended from their own iPSCs.
“The idea is very simple,” says UW-Madison neuroscientist Prof. Su-Chun Zhang. “When you have stem cells, you will generate the right type of target cells in a steady manner. So when they result from the individual you intend to graft them into, your body recognizes and welcomes them as their own.”
Prof. Zhang and his colleagues spent years creating a technique to generate stem cells that become dopamine neurons well suited for transplanting into brains.
To determine whether cells created in this manner have the potential to reverse symptoms in humans, they have finally successfully tested the approach in animals.
Motor and social skills
First, the scientists used a neurotoxin to induce a Parkinson’s-like condition in 10 adult rhesus macaques.
For several years, Prof. Emborg’s lab conducted monthly assessments of the animals’ motor and social skills. Furthermore, they used an imaging technique called positron emission tomography (PET) to gauge the quantity of dopamine stated in their brains.
“We evaluated through observation and scientific tests how the animals walk, how they grab bits of food, how they interact with people - and in addition with PET imaging, we measured dopamine production,” says Prof. Emborg.
“We wanted symptoms that resemble an adult stage of the condition,” she explains.
All of the animals developed persistent signs of Parkinson’s, including slow movement, problems with balance, and tremors. In addition they showed symptoms that resemble depression and anxiety in people, such as for example pacing their cages, socially isolating, and lacking interest in edible treats.
Next, the researchers injected half of the animals with an incredible number of dopamine neurons and supporting cells from healthy monkeys, known as “allogenic” transplants.
They injected the other monkeys with cells produced from the animals’ own iPSCs, referred to as “autologous” transplants.
The site of the injections was the striatum, which is a the main midbrain that becomes deficient in dopamine in Parkinson’s disease.
Source: www.medicalnewstoday.com