Designer neurons bring hope for treatment of Parkinson’s disease


It is known that neurodegenerative diseases damage and destroy neurons, thus destroying the mental and physical health of the person. Parkinson’s disease, which affects more than 10 million people worldwide, is no less.

The disease first deprives the brain of dopamine – damaging a specific class of neurons located in the midbrain – causing the affected person to exhibit the most apparent symptoms of rigidity, tremor and postural instability.

Additional effects of Parkinson’s disease can include depression, anxiety, memory deficit, hallucinations, and dementia.

Cases of Parkinson’s disease are expected to affect more than 14 million people worldwide by 2040. Current treatments, which include the use of the drug L-DOPA, can only treat some of the motor symptoms of the disease and can produce serious, often intolerable side effects. effects after ten years of use.

There is good news, however.

A radical strategy

Stem cell replacement therapy, or regenerative medicine, opens a radical avenue for the treatment of Parkinson’s disease and other neurodegenerative diseases.

The futuristic approach will soon be put to the test in the first clinical trial of its kindin a specific population of people with Parkinson’s disease, carriers of a parkin gene mutation.

The research has been published in the current issue of the journal npj Natural regenerative medicine.

“We couldn’t be more excited about the opportunity to help people who suffer from this genetic form of Parkinson’s disease, but the lessons learned from this trial will also have a direct impact on patients who suffer from sporadic or non-genetic factors of this disease,” said Jeffrey Kordower, founding director of the ASU-Banner Center for Neurodegenerative Disease Research and Charlene and J. Orin Edson Distinguished Director at the Biodesign Institute at Arizona State University.

The result can reverse motor symptoms

The trial will be conducted at various locations, including the Barrow Neurological Institute in Phoenix, with Kordower as the principal investigator.

In the research, Kordower and his colleagues describe a process for converting non-neuronal cells into functional neurons capable of taking up residence in the brain, extending their fibrous branches through neural tissue, forming synapses, releasing dopamine and restore the capacities undermined by the destruction of Parkinson’s. of dopaminergic cells.

The current proof-of-concept study reveals that a group of experimentally designed cells perform optimally in terms of survival, growth, neuronal connectivity and dopamine production when implanted in the brains of rats.

The study demonstrates that the result of such neural transplants is to effectively reverse motor symptoms due to Parkinson’s disease.

The new study describes the implantation of induced pluripotent stem cells (iPSCs) to replace dopamine-producing neurons destroyed by Parkinson’s disease. Source: Shireen Dooling/Arizona State University Biodesign Institute

How it works?

It’s not that easy, however.

Adult stem cells come in two varieties. One type can be found in fully developed tissues like bone marrow, liver, and skin. The second type of adult stem cells – the focus of this study – is known as induced pluripotent stem cells (iPSCs).

The iPSC production technique used in the study takes place in two phases.

First, adult blood cells are treated with specific reprogramming factors that turn them back into embryonic stem cells. The second phase treats these embryonic stem cells with additional factors, causing them to differentiate into the desired target cells, the dopamine-producing neurons.

“The main takeaway from this paper is that the timing of when you give the second set of factors is critical,” Kordower says. “If you treat them and culture them for 17 days, then stop their divisions and differentiate them, it works better.”

Can we expect a complete reversal?

Rats treated with 17-day iPSCs showed remarkable recovery from motor symptoms of Parkinson’s disease. The study further demonstrated that this effect is dose-dependent.

When a small number of iPSCs were transplanted into the animal’s brain, recovery was negligible, but a large number of cells produced more abundant neural branching and a complete reversal of Parkinson’s disease symptoms.

The initial clinical trial will apply iPSC therapy to a group of patients with Parkinson’s disease who carry a particular genetic mutation, known as the Parkin mutation.

Larger trials will follow if the treatment is effective.

Once effective, a useful tool for treating a wide range of diseases

The treatment could also potentially be combined with existing therapies to treat Parkinson’s disease. Once the brain has been seeded with replacement dopamine-producing cells, lower doses of drugs like L-DOPA could be used, enhancing beneficial outcomes and mitigating side effects.

Such research sets the stage for the replacement of damaged or dead neurons with fresh cells for a wide range of devastating diseases.

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

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