While Huntington disease, a progressive brain disorder, is inherited in an autosomal dominant pattern, Johns Hopkins’ researchers believe their discovery about how the disease progresses could lead to a way to stall it.
The 30,000 Americans, who are living with Huntington, along with another 200,000 at risk of inheriting the disease, could benefit from these findings. They could also prove to be a valuable tool for researchers, helping to learn more about how the brain changes with age and understanding other neurological diseases, such as amyotrophic lateral sclerosis (ALS).
“We found these kind of traffic jams in cells, and if we can fix the traffic jams we can potentially provide a new avenue for treatment of neurodegenerative disease,” said Jonathan Grima, a graduate student in the Department of Neuroscience at Johns Hopkins University.
Grima questions if a drug developed to clear these jams could also stop cells from dying and stall the progression of Huntington disease. However, he said it is the goal to develop a drug that could do both. Other scientists are being encouraged to build on the findings in search for a treatment.
Researchers from the University of California-Irvine, University of Florida and other departments at Johns Hopkins have partnered with the Huntington’s researchers to demonstrate how Huntington disrupts normal cell activity.
Proteins and salts, components of a brain cell, must move in and out of the nucleus, the central core of a cell, in order for it to function properly. The HTT gene that causes Huntington disease produces proteins that clump together in the nucleus, so they cannot pass through the nuclear pores, special passageways. Each cell has a large number of nuclear pores, but if the proteins cannot pass through them freely, the cell will shut down and die.
Scientists were familiar with the HTT gene and nuclear pores, but they didn’t know about clumping of proteins, clogging of pores or the breakdown in the so-called nuclear transport.
“This is very exciting research because we didn’t know what mutant genes or proteins were doing in the body, and this points to a new areas to target research,” said George Yohrling, senior director of mission and scientific affairs at the Huntington’s Disease Society of America. “Scientists, biotech companies and pharmaceutical companies could capitalize on this and maybe develop therapies for this biological process.”
There are currently two treatments available for Huntington disease, with one just approved by the U.S. Food and Drug Administration (FDA) in the past few weeks. Both of these drugs help improve mobility and gait problems that are associated with Huntington disease.
However, there are no drugs available that will slow or stop the progression of the disease. Sufferers lose the ability to speak, walk and reason over 10 to 25 years after initial diagnosis. The onset of symptoms will appear between the ages of 30 and 50, with 50 percent chance of passing the HTT gene to offspring.
According to the director of the Translational Neurotherapeutics Program at Georgetown University Medical Center, Charbel Moussa, an effective treatment will consist of a variety of drugs, which will stop disease progression and control symptoms.