Home Science & Technology Designer neurons give new hope for the treatment of Parkinson’s disease

Designer neurons give new hope for the treatment of Parkinson’s disease

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Neurodegenerative diseases damage and destroy neurons, destroying both mental and physical health. Parkinson’s disease, which affects more than 10 million people worldwide, is no exception. The most obvious symptoms of Parkinson’s disease occur after the disease damages a certain class of neurons located in the midbrain. The effect is to deprive the brain of dopamine – a key neurotransmitter produced by the affected neurons.

In a new study, Jeffrey Cordover and colleagues describe the process of transforming non-neuronal cells into functioning neurons capable of settling in the brain, sending their fibrous branches through nerve tissue, forming synapses, releasing dopamine and restoring abilities undermined by the destruction of Parkinson’s dopaminergic cells.

The current study confirming the concept shows that one group of experimentally created cells works optimally in terms of survival, growth, neural communication and dopamine production when implanted in the rat brain. Research shows that the result of such neuronal transplants is an effective change in motor symptoms due to Parkinson’s disease.

Stem cell replacement therapy is a new radical strategy for the treatment of Parkinson’s disease and other neurodegenerative diseases. A futuristic approach will be tested soon the first of its kind clinical trial, in a certain population of Parkinson’s patients who have a mutation in the parkin gene. The test will be conducted at a variety of locations, including at the Barrow Neurological Institute in Phoenix, and Cordower will be the lead researcher.

The work is supported through a grant from the Michael J. Foundation. Fox.

“We can no longer be happy to be able to help people with this genetic form of Parkinson’s disease, but the lessons learned from this test will also directly affect patients with sporadic or non-genetic forms of the disease,” Cordauer said. I say.

Cordower manages ASU-Banner Center for the Study of Neurodegenerative Diseases at the University of Arizona and is Honored Director of Charlene & J. Orin Edsanov Institute of Biodesign. The new study details the experimental preparation of stem cells suitable for implantation to reverse the effects of Parkinson’s disease.

The study appears in the current issue of the journal npj Nature is restorative medicine.

New views on Parkinson’s disease

You don’t need to be a neurologist to identify a neuron. Such cells with their branched outgrowths of axons and dendrites are instantly recognizable and unlike any other cell type in the body. With their electrical impulses, they carefully control everything from pulse to speech. Neurons are also a repository of our hopes and anxieties, a source of our individual identity.

Degeneration and loss of dopaminergic neurons causes the physical symptoms of rigidity, tremor, and postural instability that characterize Parkinson’s disease. Additional consequences of Parkinson’s disease may include depression, anxiety, memory deficits, hallucinations, and dementia.

Due to the aging population, humanity is facing a growing crisis of Parkinson’s disease, and by 2040 their numbers are expected to increase to more than 14 million worldwide. motor symptoms of the disease and can cause serious, often unbearable side effects after 5-10 years of use.

There is no cure that can reverse Parkinson’s disease or stop its relentless development. Far-sighted innovations are urgently needed to address this emergency.

A powerful weapon against Parkinson’s disease

Despite the intuitive appeal of simply replacing dead or damaged cells to treat neurodegenerative diseases, the challenges for successfully implanting viable neurons to restore function are formidable. Many technical hurdles had to be overcome before researchers, including Cordauer, were able to begin to achieve positive results using a class of cells known as stem cells.

Interest in stem cells as an attractive therapy for a number of diseases quickly gained momentum after 2012, when John B. Gourdan and Shinya Yamanaka shared the Nobel Prize for a breakthrough in stem cell research. They showed that mature cells can be reprogrammed, making them “pluripotent” or able to differentiate into any type of cell in the body.

These pluripotent stem cells are functionally equivalent to fetal stem cells that thrive during embryonic development, migrating to their habitat and transforming into heart, nerve, lung and other cell types, in one of the most remarkable transformations in nature.

Neural alchemy

Adult stem cells come in two varieties. One type can be found in fully developed tissues such as bone marrow, liver and skin. These stem cells are few and usually develop into the type of cells that belong to the tissue from which they are derived.

The second type of adult stem cell (and the focus of this study) is known as induced pluripotent stem cells (iPSC). The technique of obtaining IPSC, used in the study, occurs in two stages. In a sense, cells are induced to travel in time, first in reverse and then forward.

First, adult blood cells are processed by certain reprogramming factors that cause them to return to embryonic stem cells. The second phase treats these embryonic stem cells with additional factors, forcing them to differentiate into the desired target cells – neurons that produce dopamine.

“The main conclusion in this article is that the time you give the second set of factors is crucial,” Cordower says. “If you treat and cultivate them for 17 days and then stop their divisions and differentiate them, it works best.”

Perfect tone of neurons

The study experiments included iPSCs cultured for 24 and 37 days, but those that were cultured for 17 days before differentiating into dopaminergic neurons were noticeably better, able to survive in greater numbers and send their branches over long distances. “It’s important,” Cordover says, “because they have to grow long distances in the larger human brain, and now we know these cells are capable of that.”

Rats treated with 17-day iPSCs showed excellent recovery from motor symptoms of Parkinson’s disease. The study also shows that this effect is dose dependent. When a small amount of IPSC was inoculated into the animal’s brain, recovery was negligible, but a large number of cells caused more abundant nerve branching and a complete change in Parkinson’s symptoms.

The first clinical study will apply iPSC therapy to a group of patients with Parkinson’s disease who have a specific genetic mutation known as the Parkin mutation. Such patients suffer from typical symptoms of motor dysfunction that occur in general or idiopathic Parkinson’s disease, but do not suffer from cognitive decline or dementia. This cohort of patients is an ideal testing ground for cell replacement therapy. If the treatment is effective, larger trials will follow, applying this strategy to the version of Parkinson’s disease that affects most patients affected by the disease.

In addition, treatment could potentially be combined with existing Parkinson’s disease treatments. Once the brain has been inoculated with dopamine-producing replacement cells, lower doses of drugs such as L-DOPA can be used, which alleviate side effects and improve beneficial outcomes.

The study creates the ground for replacing damaged or dead neurons with fresh cells for a wide range of destructive diseases.

“Patients with Huntington’s disease, multiple system atrophy, or even Alzheimer’s disease could be treated this way for certain aspects of the disease process,” Cordower says.

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