The Huntington’s Disease Society of India (HDSI) recently held its second annual meeting in Bengaluru, a crucial gathering that united patients, their families, dedicated researchers, and expert clinicians all focused on Huntington’s disease (HD).
Sheeba Vasu, a professor of neuroscience at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bengaluru, emphasized the profound impact of these meetings. She noted, “Studying laboratory models of HD doesn’t fully capture the experience, but directly meeting patients has been incredibly insightful for both me and my students,” underscoring the importance of bridging the gap between scientific study and lived experience.
Huntington’s disease is a devastating genetic neurodegenerative disorder. It manifests as severe motor issues, including involuntary jerky movements, muscle stiffness, and speech difficulties. Patients also face significant cognitive impairments, affecting learning and planning, alongside psychiatric struggles such as personality shifts, depression, anxiety, extreme irritability, and unpredictable mood swings. Symptoms usually emerge in adulthood, between 30 and 55 years of age, and steadily worsen over time, ultimately proving fatal.
The root cause of HD is a dominant mutation in the Huntingtin gene. This gene typically produces a vital scaffolding protein involved in neuron development, molecular transport within cells, and gene regulation.
Pavitra Prakash, who completed her PhD at JNCASR researching an HD fruit fly model, explained that this protein normally plays a protective role, but unfortunately, “it turns toxic in its mutant form.”
In its mutated state, the Huntingtin gene contains an excessive number of repeating genetic codes for the amino acid glutamine, known as polyQ repeats. The severity of the disease and the age at which symptoms first appear are directly linked to the quantity of these repeats; typically, more than 35-40 repeats result in Huntington’s disease.
Current estimates suggest that between 20,000 and 40,000 individuals in India are living with Huntington’s disease.
Prashanth Kukkle, a consultant neurologist from Bengaluru’s Parkinson’s Disease and Movement Disorders clinic, clarified, “Without comprehensive epidemiological studies, this figure is our best estimate, derived from our 2021 review. However, it’s possible that over 200,000 people could be at risk.”
Unlocking Secrets with Fruit Flies
Remarkably, a small insect, the fruit fly (Drosophila melanogaster), has provided crucial insights into the mechanisms of Huntington’s disease. For decades, Drosophila has been a staple in genetic research. It became a valuable model for HD in the late 1990s when scientists discovered they could introduce and express specific genes within the insect’s tissues. Since HD is caused by a single gene mutation, researchers could effectively introduce the mutant human Huntingtin gene into fly tissues and closely observe how the disease developed.
This fruit fly model faithfully reproduces all the key features of Huntington’s disease, enabling scientists to study the condition comprehensively at molecular, cellular, behavioral, and systemic levels.
The compound eye of the fruit fly serves as a prime example. Dr. Prakash explained, “Typically, its precisely organized clusters of photoreceptors appear smooth when viewed under a microscope. However, with neurodegeneration, this intricate structure deteriorates, resulting in a ‘rough’ eye appearance.”
The degree of this ‘roughness’ directly correlates with disease progression, proving invaluable for conducting large-scale drug screenings.
Sleep disturbances, another characteristic symptom of HD, are also effectively replicated in fruit flies. Sheeba Vasu’s laboratory, among others, developed a circadian rhythm model by expressing mutant Huntingtin genes in the neurons responsible for regulating daily biological clocks. Much like humans, flies exhibit strong sleep-wake cycles. However, these rhythms disintegrate as neurodegeneration progresses. The speed of this breakdown is directly linked to the number of polyQ repeats: flies with 50 repeats lose their rhythmicity approximately two weeks into adulthood, whereas those with 93 repeats lose it within just two days.
Measuring motor disturbances is also straightforward. Dr. Prakash noted, “For example, we track the time it takes for flies to cover a specific distance. Consistently, flies carrying the defective Huntingtin gene are slower than those with the normal version.”
Leveraging this fly model, researchers Subramaniam Ganesh and Deepashree Sheshadri at IIT-Kanpur discovered that glycogen synthase, an enzyme crucial for producing glycogen, offers a protective effect.
Mr. Ganesh reported that “boosting its levels significantly lessens HD symptoms in fruit flies, enhancing their survival, improving their movement, preserving neuronal integrity, and positively impacting crucial molecular indicators.”
However, researchers emphasize that discoveries in fruit flies represent just the initial stage. Ms. Sheshadri explained, “While the potential for glycogen modulation as a safe and effective treatment is still unconfirmed, the fly model allows us to quickly test activators of glycogen synthase before progressing to more complex mammalian models.”
Dance: A Rhythmic Path to Therapy
Outside the confines of the laboratory, scientists are also investigating complementary approaches to alleviate HD symptoms and enhance quality of life. Several studies have already demonstrated that structured movement, particularly through dance forms such as the Argentine tango, can help patients with Parkinson’s disease recover some motor control.
Emerging research indicates that dance could also benefit Huntington’s disease patients in managing their movement challenges. For instance, a 2013 study in Clinical Rehabilitation explored the impact of the video game ‘Dance Dance Revolution,’ which requires players to mimic on-screen dance steps. After participating in 45-minute sessions twice a week for six weeks, patients demonstrated improved gait and balance compared to a control group who played a handheld video game.
A separate study published in 2019 in the Journal of Huntington’s Disease provided contemporary dance classes at least once a week over five months. Participants in the dance group exhibited improved movement scores, enhanced verbal fluency, and a better mood compared to those receiving only standard care. Notably, patients in this study were eager to continue their dance classes even after the trial concluded.
Though these findings are encouraging, more extensive studies are necessary to definitively confirm if dance therapy can consistently alleviate HD symptoms.
Despite the need for further research, medical professionals are approaching these possibilities with cautious optimism.
Dr. Kukkle stated, “Dance, music therapy, and any form of mind-body relaxation have shown positive outcomes. We advocate for these approaches in managing Huntington’s disease and other movement disorders.”
During the conference, dancer and teacher Daksha Mashruwala introduced Odissi as a potential choreographic therapy specifically for HD patients. Collaborating with a physiotherapist, she developed a program incorporating the controlled movements of Odissi mudras (hand gestures) and the stable chauka (square) stance to help patients counteract their involuntary movements. Additionally, weighted waistbands and anklets can assist in improving trunk mobility, gait, and hand control.
She explained, “Our aim is for Odissi to serve as a complementary therapy to conventional treatment, simultaneously providing patients with an opportunity for social engagement with other learners.” This highlights dance’s dual benefit for both physical improvement and social interaction.
However, even with advancements in science and therapy, patients and their families continue to grapple with profound challenges.
Ms. Sheeba stressed the critical need for a patient registry, explaining, “This registry would facilitate patient enrollment in clinical trials, broaden the network of doctors specializing in HD, and significantly increase awareness about the disease.”
Despite a network of over 200 families connected via a WhatsApp group, formal registration remains low. Significant obstacles, including privacy concerns and the strong social stigma associated with HD, hinder not only the creation of a comprehensive registry but also broader efforts to enhance the daily lives of patients.
This article was written by Sheetal Potdar, who holds a PhD in neuroscience and works as a science writer.