Parkinson’s disease is a progressive nervous system disorder that affects movement. The signs and symptoms can be different for everyone, but can include tremors, rigid muscles, and loss of automatic movements. Additional problems may include depression, cognitive difficulties, sleep problems, and more. Patients are typically treated with drugs like L-DOPA to increase dopamine production. However, the effect does not last, and patients are back to not having enough dopamine and facing side effects from the drug. Now, researchers at the University of Wisconsin (UW)-Madison report they have grafted neurons grown from monkeys’ own cells into their brains and relieved the debilitating movement and depression symptoms associated with Parkinson’s disease.
Their findings were published in the journal Nature Medicine in a paper titled, “Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys.”
“Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson’s disease (PD),” the researchers wrote. “Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons.”
The researchers demonstrated that over a two-year period without immunosuppression, PD monkeys receiving autologous transplantation exhibited recovery from motor and depressive signs.
UW-Madison neuroscientist Su-Chun Zhang, MD, PhD, professor, neuroscience and neurology, whose Waisman Center lab grew the brain cells, has spent years learning how to dial donor cells from a patient back into a stem cell state, in which they have the power to grow into nearly any kind of cell in the body.
“The idea is very simple,” Zhang stated. “When you have stem cells, you can generate the right type of target cells in a consistent manner. And when they come from the individual you want to graft them into, the body recognizes and welcomes them as their own.”
“We evaluated through observation and clinical tests how the animals walk, how they grab pieces of food, how they interact with people—and also with PET imaging we measured dopamine production,” explained Marina Emborg, MD, PhD, a Parkinson’s researcher at UW-Madison’s Wisconsin National Primate Research Center. “We wanted symptoms that resemble a mature stage of the disease.”
Utilizing real-time MRI, the researchers injected millions of dopamine-producing neurons and supporting cells into the striatum, an area of the brain that is depleted of dopamine as a consequence of Parkinson’s. Half the monkeys received a graft made from their own induced pluripotent stem cells, and half received cells from other monkeys, an allogenic transplant.
The researchers observed that the monkeys that got grafts of their own cells, were making significant improvements after six months. Within a year, their dopamine levels had doubled and tripled.
“The autologous animals started to move more,” Emborg noted. “Where before they needed to grab the cage to stand up, they started moving much more fluidly and grabbing food much faster and easier.”
The monkeys who received allogenic cells, however, showed no such lasting boost in dopamine or improvement in muscle strength or control.
“They could grow freely and extend far out within the striatum,” added Yunlong Tao, PhD, a scientist in Zhang’s lab and first author of the study. “In the allogenic monkeys, where the grafts are treated as foreign cells by the immune system, they are attacked to stop the spread of the axons.”
“Although Parkinson’s is typically classified as a movement disorder, anxiety and depression are typical, too,” Emborg said. “In the autologous animals, we saw extension of axons from the graft into areas that have to do with what’s called the emotional brain.”
These findings take an important step forward to treating Parkinson’s disease. The researchers hope results can move them into clinical application.
