Neuroscientists Use Genetic Screen to Identify Huntington’s Disease Drug Targets

By Jodee Redmond from In The Cloud Copy

Massachusetts Institute of Technology (MIT) researchers have recently announced they have identified hundreds of genes that are required for neuron survival. The neuroscientists used the same genetic screen to identify genes that can provide some protection against the harmful effects of a mutant protein responsible for Huntington’s disease.

What is Huntington’s Disease?

Huntington’s disease is a genetic disorder which causes brain nerve cells to break down in affected patients, leading to a progressive deterioration in their physical and cognitive abilities. There is no cure for this fatal disease, although its symptoms are treatable.

If one parent has Huntington’s disease, each of their children has a 50% chance of inheriting the gene responsible for the disorder. According to the Huntington’s Society of America, about 41,000 Americans are living with the disease. Another 200,000 people are at risk of inheriting Huntington’s.

Symptoms of Huntington’s generally start to appear between 30-50 years of age. They can include the following:

  • Depression
  • Difficulty swallowing
  • Forgetfulness
  • Impaired judgment
  • Involuntary movements
  • Mood swings
  • Slurred speech
  • Unsteady gait
  • Weight loss (significant)

The symptoms become worse over the next 10-25 years, ultimately ending the patient’s life due to heart failure, pneumonia, or other health complication.

Researchers Screened Complete Set of Chromosomes

For several years, scientists have been conducting screens where they carefully eliminate genes in organisms like fruit flies, mice and C. elegans (a type of worm). Their next step is to note its effects on survival.

Tests on a mouse brain have only recently been performed, the main reason being that positioning the required molecular machinery for the genetic manipulations is more challenging when working in the brain than in other parts of the body.

Researchers from the Broad Institute have successfully developed libraries of genetic material. They can be used to turn off all the genes found in the mouse genome. The libraries are carried to the mouse by way of viruses. Each virus carries an element that targets a specific gene.

Family of Genes May Help Huntington’s Patients

MIT’s research team found a method to make their viral solution highly concentrated. Next, they injected it into the mouse’s striatum, which is the part of the brain where the lesions caused by Huntington’s disease occur.

The neuroscientists’ screening technique allowed them to evaluate all 22,000 genes of a mouse brain. Their work found at least one drug target for Huntington’s – a family of genes that may help cells break down the mutated protein before it can fuse. This protein then forms clumps which can be detected in the brains of Huntington’s patients.

Myriam Heiman, the senior author of the study and an associate professor of neuroscience in the Department of Brain and Cognitive Sciences, said that these genes had not been associated with Huntington’s disease processes before. The researchers found that they affected two models of Huntington’s disease. Heiman explained the technique could also be used for research on other types of neurological disorders, such as Parkinson’s disease and Alzheimer’s disease.

Check out the original study here.


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