New Stem Cell Model to Test Treatments for a Rare Neurodegenerative Disorder

Researchers have managed to develop a new stem cell model to assess a rare nervous system disorder that is placed in the same disease group as Parkinson’s disease, ALS (amyotrophic lateral sclerosis) and the Alzheimer’s disease.

A breakthrough in handling the rare disease would pave the way to treating most if not all neurodegenerative conditions in the same class.

The study, set up by a City of Hope researcher Yanhong Shi, Ph.D. and her colleagues is said to be likely a step closer to curing or slow neurodegenerative disorders like the Alzheimer’s disease and the rest.

A Glimpse at Alexander Disease

Source: jneurosci

The condition picked by the Shi and her team is the rare Alexander disease and the reason they chose it is because it has a relatively simple pathology. That is, its progressive nature and effects are traceable in the patient with ease.

In Alexander disease, there is a mutation process that involves a glial cell called astrocytes. This inhibits precursor cells that eventually become myelin, a fatty sheath that enhances communication in and across neural networks of the brain.

Inside astrocyte is a special gene called ApoE4 which is known to be responsible for increasing the risk of Alzheimer’s disease.

“That means if we can master how astrocytes function it would be possible to create therapies to combat the Alexander disease, and not only it, this same concept can lead us to treat other neuro-related diseases that involve astrocytes –which include ALS and Alzheimer’s,” said City of Hope’s director of Stem Cell Biology, Shi.

The Model

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In the report, which also appears in the recent issue of the journal Cell Stem Cell, researchers have managed to beat what was known as the challenge in understanding how gene mutations that involve astrocytes inhibit myelin distribution.

Nobody ever created an animal-centered model that was able to analyze the disease path before. The breakthrough happened at Shi Lab where Li Li and Shi led a team of graduate students, and they successfully created the stem cell model in question.

The model offers great insight as it allows the experts to track the disease pathway of Alexander disease. Top on that the investigators also developed a platform that allows testing of therapeutic treatments for the other neurodegenerative diseases.

Patient-derived Stem Cell

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To ensure preciseness in tackling the rare condition, the researchers created patient-derived stems that allow mutation in the GFAP gene. They then compared the cells with others harvested from Alexander disease victims. Analysis showed that both models exhibited protein deposits associated with disease, which they call Rosenthal fibers.

After that, they took a gene-editing tool CRIPSR/Cas9 and used it to correct the GFAP mutation located inside the diseased astrocytes. The observation was that after the correction, the protein deposits from GFAP mutation drastically reduced.

The researchers then used the new model to study how Alexander disease develops. They found out that astrocytes do inhibit the development of special cells by the name oligodendrocytes progenitor that converts to become myelin. See, that means interrupting the brain’s communication network to a serious extent.

Further comparison of the genes conveyed in the astrocytes harvested from stem cells of Alexander disease victims and those from healthy ones established that GFAP mutant astrocytes produce the protein CHI3L1 –discovered to suppress myelination and other neural development-related processes.

Parting Short

The study is one of a kind because this is the first research to fully understand the role of astrocytes in relation to neurological diseases and normal brain function.

However, with all this valuable information, the conclusion is that therapies that could target the protein CHI3L1 might effectively treat conditions like the leukodystrophic disease and Alexander’s diseases which both thrive by decreasing myelin.

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