Engineered neurons might assist with treatment of Parkinson's

Engineered neurons might assist with treatment of Parkinson's ...

Neurodegenerative diseases have caused both mental and physical health to lose weight. Parkinsons disease, which causes over 10 million people worldwide, is no exception. The most obvious symptoms of Parkinsons disease are when the illness develops a specific type of neuron located in the middle brain. The effect is to rob the brain of the affected neurons.

In a recent study,Jeffrey Kordower and his colleagues describe a technique for converting non-neuronal cells into functional neurons capable of acquiring residence in the brain, sending out their fibrous branches across neural tissue, form synapses, administer dopamine, and restore capacity undermined by Parkinson''s destruction of dopaminergic cells.

A recent proof-of-concept study reveals that one group of experimentally engineered cells performs optimally in terms of survival, growth, neural connectivity, and dopamine production, when implanted in rats'' brains. The study demonstrates that such neural grafts can effectively reverse motor symptoms due to Parkinsons disease.

The future approach for stem cell replacement therapy is expected to take place in the first clinical trial of its kind in a specific group of Parkinsons disease patients, with a mutation in the gene parkin. The trial will be conducted at several locations, including the Barrow Neurological Institute in Phoenix, with Kordower as its chief investigator.

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

We cannot be more saddened by the possibility of assisting individuals who suffer from this genetic form of Parkinsons disease, but the lessons learned from this study will also impact patients who have this disease, according to Kordower.

Kordower is the Distinguished Director of the Biodesign Institute for theASU-Banner Neurodegenerative Disease Research Center. The study explains in detail how stem cells are used for the treatment to reverse the effects of Parkinsons disease.

The new paper of the npj journalNature Regenerative Medicine discusses the findings.

New perspectives on Parkinsons disease

You must be a neuroscientist to identify a neuron. Such cells, with their branching arbor of axons and dendrites, are instantly recognizable and look like no other cell type in the body. Through their electrical impulses, they exert meticulous control over everything from heart rate to speech. Neurons are also the source of our individual identity.

Degeneration and the loss of dopaminergic neurons cause physical symptoms of rigidity, tremor, and postural instability, which characterize Parkinsons disease. Other symptoms of Parkinsons disease include depression, anxiety, memory deficit, hallucinations, and dementia.

Due to a rising population, humanity is preparing to face a growing wave of Parkinsons disease cases, with more than 14 million people expected to be in the world by 2040. Current medications, including the use of the medication L-DOPA, are only able to address some of the disease''s motor symptoms and may have significant, often fatal side effects after 5-10 years of exposure.

There is no treatment that might reverse Parkinsons disease or hinder its innocuous progress. These are essential ideas that are clearly visible to address this difficult situation.

A (pluri) potent weapon against Parkinsons

Despite the straightforward ability of simply replacing dead or damaged neurons in order to treat neurodegenerative disease, the difficulties of successfully implanting viable neurons to restore function are huge. However, many technical hurdles have to be overcome before researchers, including Kordower, can begin achieving positive results by employing a variety of stem cells.

After 2012, the interest in stem cells as an attractive therapy for a wide spectrum of diseases quickly gained momentum. They showed that mature cells can be reprogrammed, making them pluripotentor capable of divising into any cell type in the body.

These pluripotent stem cells are functionally similar to fetal stem cells, which flourish durant their embryonic development, migrating to their residence and developing into heart, nerve, lung, and other cell types, in one of nature''s most remarkable transformations.

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 small in size and generally develop into the type of cells belonging to the tissue they are formed.

The second type of adult stem cells (and the focus of this study) are often called induced pluripotent stem cells. The technique used in the study involves two phases. In a way, the cells are induced to time travel, in a backward and then a forward direction.

Adult blood cells are treated with reprogramming factors that cause them to revert to embryonic stem cells. The second phase includes embryonic stem cells, which are able to differentiate into the desired target cellsdopamine-producing neurons.

The important fact in the present paper is that the time in which you give the second set of factors is crucial. If you treat and culture them for 17 days, then stop their divisions and differentiate them, it works the best.

Pitch perfect neurons

iPSCs were used for 24 and 37 days before their differentiation into dopaminergic neurons. That''s why Kordower believes that they''ll have to travel long distances in the larger human brain. These cells are now fully aware of that.

Rats treated with 17-day iPSCs showed a clear recovery from Parkinsons disease''s motor symptoms. The study further demonstrates that this effect is dose dependent. However, a small number of iPSCs were removed from the animal brain, so recovery was negligible, but a large complement of cells also resulted in more profuse neural branching and reversal of Parkinsons symptoms.

The initial clinical study will include iPSC therapy to a group of Parkinsons patients with a specific genetic mutation, known as a Parkin mutation. Such patients have developed the ideal training environment for cell replacement therapy, although these patients do not have the potential to experience cognitive decline or dementia. The following cohort will follow a similar approach, focusing on the version of Parkinsons that affects most individuals with the disease.

Further, the treatment might be combined with existing therapies to treat Parkinsons disease. After the brain has been seeded with dopamine-producing replacement cells, lower doses of medications such as L-DOPA may be used, minimizing side effects and enhancing beneficial results.

The research lays the foundation for the replacement of damaged or dead neurons with fresh cells for a wide range of dangerous illnesses.

Patients with Huntington''s disease, or multiple system atrophy, or even Alzheimer''s disease may be treated in this way for specific aspects of the disease process, according to Kordower.

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