Huntington disease is a complex neurodegenerative disorder significantly affecting cognitive and behavioral functions. Dr. Karen E. Anderson, a professor at Georgetown University School of Medicine, discussed the genetic factors influencing the progression and symptoms of the disease in a recent interview.
In 2018, the Huntington Study Group and the European Huntington’s Disease Network released comprehensive guidelines for managing behavioral symptoms associated with Huntington disease. These guidelines are based on expert consensus as there have been no large randomized clinical trials focusing specifically on behavioral symptoms. Although the guidelines have not been formally updated, recent reviews have discussed new medications and strategies for symptom management.
Cognitive symptoms are also crucial in Huntington disease, and while treatment options are limited, ongoing trials represent significant progress. Sage Therapeutics is conducting studies exploring their NMDA modulator as a potential treatment for cognitive impairment in Huntington disease. Keeping updated on such developments is essential, as they may lead to improved cognitive symptom management.
There are now more resources available for symptomatic and end-of-life care, which can assist families and caregivers in navigating home and professional care settings. Social workers with expertise in Huntington disease can address various social challenges faced by patients.
At the CHDI Foundation’s recent therapeutic conference, the focus was on how increasing CAG (cytosine-adenine-guanine) repeats in somatic tissues contribute to disease progression. Dr. Anderson noted the complexity of this aspect, indicating that while it is a significant component, it does not fully explain disease progression. She highlighted that Huntington disease affects the entire body, not just the brain, and understanding the implications of CAG repeat expansion could have therapeutic relevance.
Regarding genetics and DNA repair mechanisms in Huntington disease, Dr. Anderson suggested that some of the disease pathology may arise from the body’s attempts to repair faulty DNA, potentially creating long repeats through DNA mismatch repair. She believes that finding ways to halt these faulty repair processes might help slow disease progression. Additionally, reducing huntingtin protein levels remains a critical component of treatment strategies.
With an average survival of 15 to 18 years after the onset of symptoms, late-stage Huntington disease patients face several mortality-related risks. Common issues include complications similar to those seen in elderly nursing home residents, such as urinary tract infections, pneumonia, and falls that can result in severe injuries. Rapid weight loss, choking, and swallowing difficulties also signify a patient may be nearing the end of life.
As for anti-inflammatory therapies, no approved treatments currently exist for Huntington disease, although some have been investigated. Chronic inflammation, which can disrupt normal brain function and lead to neurotoxicity, may play a significant role in the disease’s pathology. Researchers are exploring methods to suppress the abnormal immune response that occurs early in the disease.