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IEET > Rights > Life > Access > Contributors > Maria Konovalenko

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Lisa Ellerby – Fixing the Brain with Huntington’s Disease


Maria Konovalenko
Maria Konovalenko
Ethical Technology

Posted: Nov 19, 2012

I have just got back from Oman, one of the most progressive countries in the Middle East with their healthcare system ranking 8 in the world. The reason that brought me to such an unusual destination was the Buck Advisory Council Meeting. I learned a lot there, but I would like to draw your attention to the topic of one of the three major neurodegenerative diseases – Huntington’s disease.

Dr. Lisa Ellerby is searching for ways to treat Huntington’s disease. This horrible pathology now has no cure. In general, 17% of the population had a neurological disease in 2010. That’s almost every fifth person. Having this kind of pathology is one of the major risk factors for other nasty things like diabetes. So we need to understand the basics of neuroscience and only then we can understand disease and discover the treatment. Huntington’s is a 100% genetic disorder. It is caused by the mutation in the huntingtin gene. The defect version has the CAG expansion that codes for the amino acid glutamine. Basically, the gene get extra CAG repeats, which leads to the altered constitution of the huntingtin protein, which itself leads to errors in the protein shape. This misfolding causes aggregation of the protein, and it drives neuronal cell death. The most affected region of the brain is the striatum, best known for modulation and planning of movement, and also for executive function, such as working memory. As a result of massive neuronal death the patients develop erroneous muscle coordination and cognitive decline.

So, what can we do about Huntington’s disease? Do we want to know in advance that we have the mutation and that we will all these dismaying symptoms? Do we do the genetic testing? It’s a ongoing debate, but I would definitely want to know. The more information we have about our bodies, the better our chances are to save ourselves. And I mean including the cases of untreatable diseases. You ask why? Because scientific progress goes forward inexorably. What used to have no cure now sometimes is a piece of cake for the doctors. The humanity defeated small pox and polio. I am sure it will defeat Huntington’s disease within the next couple of decades. I am sure aging itself will be defeated within the next several decades. The only question is when exactly this will happen. well, I can tell you, the more money research institutes like the Buck have, the faster the progress. And Lisa Ellerby’s work is a great example why this is true. She was able to significantly improve the symptoms of Huntington’s disease in mice by applying stem cell therapy on the animals. Dr. Ellerby’s group published an article in Cell Stem Cell where they explain how they did it. They used the induced pluripotent stem cells (iPSC) approach. By the way, this year’s Nobel Prize in Medicine and Physiology was given to Dr. Shinya Yamanaka, who first performed the reprogramming of skin cells to the state of embryonic stem cells in 2006. This amazing technique allows bringing the adult cells to their “childhood” state when they are able to choose the path in their development that they will follow, like becoming liver, or skin, or bone cells.

Lisa Ellerby used the Yamanaka’s technique to convert the mouse skin cells into induced pluripotent stem cells, which closely resemble embryonic stem cells. But these cells still had the deadly mutation. The trick was to correct the mutation and the researchers did that successfully using homologous recombination, a mechanism that our cells use to correct errors like double strand DNA beaks. The team obtained the mutation-free iPS cells and was able to convert them to neurons. This can be done by giving the stem cells certain signals using the growth factors molecules. So, these new neurons didn’t have the deleterious mutation. The researchers injected these cells into a mouse with Huntington’s disease and saw that these cells survived in the striatum. The researchers found that the replacement of the disease gene mutation reversed the phenotype of the diseased cells. The observed elevation of capase-3/7 activity in HD neuronal stem cells upon growth factor deprivation recapitulates a well-characterized disease phenotype observed in various rodent and human HD models, and correction of the genetic mutation reversed this phenotype. Also, they found that the altered mitochondrial deficits, the lower levels of BDNF, and the altered cadherin and TGF-b signaling associated with HD were corrected. This means that the induced pluripotent stem cell therapy could be an option for treating patients suffering from Huntington’s disease. More research is needed, of course in order to make the therapy translated into clinic, however this is a very good start.


Maria Konovalenko is a molecular biophysicist and the program coordinator for the Science for Life Extension Foundation. She earned her M.Sc. degree in Molecular Biological Physics at the Moscow Institute of Physics and Technology.
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