About Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System

Font : A-A+

Highlights
  • Spinocerebellar ataxia type 6 (SCA6) is a movement disorder characterized by death of Purkinje cells in the cerebellum.
  • The disease results from mutations that increase the number of times a particular section of the CACNA1A gene are repeated.
  • Researchers made a disease model based on human Purkinje cells grown in culture.
  • Researchers discovered that mature Purkinje cells with the SCA6 mutation became vulnerable when deprived of thyroid hormone.
  • The patient-derived Purkinje cells show a vulnerability to nutrient depletion and that this vulnerability can be suppressed by several compounds.

Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System

A new model system that can be used to develop drug therapies for genetic disorders like spinocerebellar ataxia type 6 (SCA6), has been created by researchers at the RIKEN Center for Developmental Biology.

SCA6 is a movement disorder characterized by death of Purkinje cells in the cerebellum, a brain region that controls our ability to produce smooth movements.

Advertisement


No effective treatment or cure exists for this neurodegenerative disorder, and animal models have proved inconclusive.

The disease manifests in middle age and results from mutations that increase the number of times a particular section of the CACNA1A gene are repeated.
Advertisement

As an alternative, the team led by Keiko Muguruma focused their efforts on making a disease model based on human Purkinje cells grown in culture.

Published in Cell Reports, the study shows how stem cells from patients with SCA6 can be transformed into mature Purkinje cells, the same type of neuron that starts dying when people develop SCA6 later in life. With this setup, the team discovered that mature Purkinje cells with the SCA6 mutation became vulnerable when deprived of thyroid hormone.

As Muguruma explains, "we succeeded in generating Purkinje cells with full sets of SCA6 patient genes. Unlike animal models, these patient-derived Purkinje cells will be extremely useful for investigating disease mechanisms and for developing effective drug therapies."

The researchers first induced skin or blood cells from patients and control participants to become pluripotent stem cells. Then they used techniques recently developed in their lab to create self-organizing cerebellar tissue and Purkinje cells.

When tested, the team found that while both types of mature Purkinje cells seemed outwardly similar, they differed in how much the CACNA1A gene was expressed.

The patient-derived cells contained more of the protein encoded by the CACNA1A gene than the normal cells. When immature cells were tested, protein expression levels were similar, regardless of their origins.

The part of the CACNA1A protein that contains the excessively repeated section is called α1ACT.

When researchers compared expression of this fragment between normal and patient-derived cells, they found that it was expressed much less in the SCA6 Purkinje cells.

Because α1ACT normally binds to DNA in the nucleus and triggers the expression of other proteins that are important for normal Purkinje-cell development, these proteins were also expressed much less in the cells that contained the mutation.

Again, when the team looked at immature Purkinje cells, α1ACT expression was similar for all groups.

"This new system is particularly useful for drug discovery," notes Muguruma. "Using it, we were able to demonstrate that patient-derived Purkinje cells show a vulnerability to nutrient depletion and that this vulnerability can be suppressed by several compounds."

Knowing that thyroid hormone is important for proper maturation and maintenance of Purkinje cells, the researchers deprived mature neurons of the hormone and found that many of the patient-derived cells died, while those that survived showed physical abnormalities. Purkinje cells without the mutation were unaffected.

Muguruma cautions, "there are some reports that hypothyroidism is related to cerebellar ataxia and cerebellar atrophy, but we do not yet know whether the SCA6 disease phenotypes are causally linked to decreased thyroid hormone."

Now that they have proved the usefulness of this model system, Muguruma and her colleagues can continue to investigate how thyroid releasing hormone was able to protect the cells, and ultimately find a cure for this type of spinocerebellar ataxia.



Source: Medindia

Citations   close

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Dr. Meenakshy Varier. (2016, November 02). Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System. Medindia. Retrieved on Aug 10, 2022 from https://www.medindia.net/news/healthwatch/treatments-for-spinocerebellar-ataxia-can-be-developed-using-the-new-model-system-164827-1.htm.

  • MLA

    Dr. Meenakshy Varier. "Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System". Medindia. Aug 10, 2022. <https://www.medindia.net/news/healthwatch/treatments-for-spinocerebellar-ataxia-can-be-developed-using-the-new-model-system-164827-1.htm>.

  • Chicago

    Dr. Meenakshy Varier. "Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System". Medindia. https://www.medindia.net/news/healthwatch/treatments-for-spinocerebellar-ataxia-can-be-developed-using-the-new-model-system-164827-1.htm. (accessed Aug 10, 2022).

  • Harvard

    Dr. Meenakshy Varier. 2021. Treatments For Spinocerebellar Ataxia Can Be Developed Using The New Model System. Medindia, viewed Aug 10, 2022, https://www.medindia.net/news/healthwatch/treatments-for-spinocerebellar-ataxia-can-be-developed-using-the-new-model-system-164827-1.htm.

Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
What's New on Medindia
Test Your Knowledge on Lung Transplantation
Baldness can be Cured and Prevented: let us see How!
Drinking Beer or Wine Every Day Could Cause Age-related Diseases
View all
Recommended Reading
News Archive
Date
Category
Advertisement
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Ataxia Spinocerebellar Ataxia 

Most Popular on Medindia

Drug Side Effects Calculator Diaphragmatic Hernia Iron Intake Calculator Turmeric Powder - Health Benefits, Uses & Side Effects Loram (2 mg) (Lorazepam) Pregnancy Confirmation Calculator Drug Interaction Checker Blood Pressure Calculator Find a Hospital Vent Forte (Theophylline)
This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use