Review of “Sustained Therapeutic Reversal of Huntington’s Disease by Transient Repression of Huntingtin Synthesis"
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Citation
Abstract
Huntington’s disease is a highly complex neurodegenerative disease that currently affects a conservative estimate of 30,000 individuals in the United States and over 500,000 worldwide. The disorder is profoundly debilitating. Symptoms typically begin developing in the affected patient’s late thirties or early forties (though they can manifest as early as infancy), and almost always result in mortality about twenty years after onset. The earliest symptoms often include subtle changes in mood and cognitive processes, followed by steadily increasing uncoordinated and jerky motor movement. Noticeable changes in personality can also take place, with individuals usually expressing mood swings and poor temperament, similar to those afflicted with bipolar disorder. The decline in motor control progresses and is usually eventually classified as chorea—symptoms resulting from any of several diseases of the nervous system characterized by jerky, involuntary movements of the face and extremities—which is also often the tell-tale sign for clinicians to diagnose a patient with Huntington’s, in conjunction with an MRI scan or other imaging technique that can confirm striatal nuclei atrophy in the brain. These saccadic agitations can affect virtually all muscle movements in the body, including involuntary facial and ocular twitches. As the disease progresses, about 3-5 years after the onset of these relatively minor motor abnormalities, clear appearance of advanced complications arise, including abnormal posturing, rigidity, and writhing, similar to patients afflicted with Parkinson’s. In its later stages, all psychomotor functions can become impaired, and advanced motor symptoms include difficulty chewing, talking, walking, and sleeping. Daily activities are thus severely impacted, and seizures are not uncommon. Around this time, cognitive abilities also become increasingly impaired—specifically,
executive functions. Social skills decline, along with planning, abstract thinking, and both episodic (personal) and procedural (skill-oriented) memories. All phases of memory (short-term, working, and long-term) can completely deteriorate, leading to a patient who no longer has a sense of self and is unable to autonomously perform any task required to carry on living.