A Promising Clue in an Age-Old Medical Cold Case

            Like the Baxley family in Mercies in Disguise, my family also harbors a frightening genetic disease. Ours is called spinocerebellar ataxia type 3, or Machado-Joseph Disease. SCA3, like other spinocerebellar ataxias, is primarily a disease of the parts of our central nervous system that coordinate movement. My maternal great-grandmother (and now, my grandmother) started losing her balance in her forties. My mom tells me other members of our family assumed she was just drunk most of the time. Losing her balance led to falls which led to broken bones which eventually led to living in a nursing home with difficulty standing or even swallowing.

My great-grandmother died of complications from her disease about a decade ago. My grandmother started showing symptoms herself around the same time and shortly thereafter underwent genetic testing to confirm she had SCA3, a fact she already instinctively knew. She’s doing decently well now and her symptoms are mild for the disease, but she’s fallen multiple times and had to undergo surgery for a broken wrist just a few weeks ago. It’s a sad and scary disease and one that, should my mother have it, I may very well inherit.

            But enough about my family. As the name SCA3 implies, it’s just one of many forms of spinocerebellar ataxia, all with similar symptoms and pathologies but with varying levels of severity, ages of onset, and exact routes of inheritance. Like SCA3, SCA1 is inherited in an autosomal dominant fashion (if you have one copy of the gene, you will develop the disease; if you have the disease, there’s a 50% chance you will pass it on to each of your children). The causative gene in SCA1 is called, fittingly, ATXN1 and both the gene and its “interacting factors were determined over two decades ago,” though therapy has remained almost nonexistent (News Medical).

            However, that might be about to change. To sum up the complex results of one recent study by Tokyo Medical and Dental University, “functional impairment of YAP/YAPdeltaC by mutant ATXN1 protein during development determines the adult pathology of SCA1” (News Medical). In layman’s terms, scientists have pinpointed the exact protein that ATXN1 affects to cause SCA1. By determining this, researchers hope to be able to develop more specific therapies for the disease.

            In another part of the world entirely, researchers at Baylor University recently completed a study that determined that the protein PUMILIO1, which regulates ATXN1 production, was found in much smaller amounts in SCA1 patients, as opposed to healthy patients. Taking it a step further, the less PUMILIO1 a patient had, the more severe and debilitating their condition was, again as opposed to healthy patients. Those with a milder form of the disease had PUMILIO1 levels between those of a healthy patient and a severely affected SCA1 patient (Medical Xpress).

           

So what does this mean? Well, in the most basic sense, it means SCA1 patients might be able to receive treatment or even a cure in the near future. As a much more profound result, it opens the door for research into other forms of SCA, since it’s likely that they, too, have a specific causative protein mechanism or mutant gene. And if we can find that, we can find a cure as well.

            And maybe we’ll have some happy endings to a lot of sad stories.

Defects on regulators of disease-causing proteins can cause neurological disease. (2018, February 22). Retrieved March 20, 2018, from https://medicalxpress.com/news/2018-02-defects-disease-causing-proteins-neurological-disease.html

Researchers uncover key protein that rescues progression of adult spinocerebellar ataxia. (2018, January 28). Retrieved March 20, 2018, from https://www.news-medical.net/news/20180127/Researchers-uncover-key-protein-that-rescues-progression-of-adult-spinocerebellar-ataxia.aspx

SCA1 - Genetics Home Reference. (n.d.). Retrieved March 20, 2018, from https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-1#genes