The Huntington’s Disease Society of India (HDSI) hosted its second annual meeting at NIMHANS, Bengaluru, in August this year, bringing together patients, caregivers, researchers, and clinicians working on Huntington’s disease (HD).
“Working on laboratory models of HD doesn’t give the full picture, but meeting patients has been eye-opening for me and my students,” Sheeba Vasu, professor of neuroscience at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru, said, highlighting the benefits of connecting scientists and patients.
HD is a genetic, neurodegenerative disease that causes motor deficits like jerky uncontrolled movements, rigidity, and speech problems; cognitive difficulties in learning and planning; and psychiatric challenges like personality changes, depression, anxiety, irritability, and frequent mood changes. The symptoms typically appear in adults aged 30-55 years and worsen progressively, eventually leading to death.
The disease is caused by a dominant mutation in a gene called Huntingtin which normally codes for a scaffolding protein with roles in neuronal development, cellular transport of molecules, and gene regulation.
“It also has a protective role, which becomes toxic in its mutant form,” Pavitra Prakash, who obtained her PhD working on a fruit-fly model of HD from JNCASR, said.
In the mutant version, the gene carries excessive repeats of the genetic code for the amino acid glutamine (Q), called polyQ repeats. The severity and age at which symptoms appear depend on the number of these repeats, with more than 35-40 leading to HD.
In India, the number of people suffering from HD is estimated between 20,000-40,000.
“In the absence of epidemiological studies, this is the best estimate based on our 2021 review, although more than two lakh people may be at risk,” said Prashanth Kukkle, a consultant neurologist at the Parkinson’s Disease and Movement Disorders clinic, Bengaluru.
Insights from fruit flies
Many valuable insights into HD mechanisms have come from an unlikely source: the fruit fly (Drosophila melanogaster). A workhorse in genetics for decades, Drosophila became a model for HD in the late 1990s when scientists found they could express any gene of interest in specific tissues in the insect. Because HD is caused by a single gene, researchers could express the mutant form of human Huntingtin in fly tissues and track disease progression.
The Drosophila model captures all the hallmarks of the disease, allowing scientists to study HD at the molecular, cellular, behavioural, and systemic levels.
The fly compound eye is an excellent example. “Normally, its neatly arranged clusters of photoreceptors appear smooth under a microscope. With neurodegeneration, this structure breaks down, producing a ‘rough’ eye,” Dr. Prakash said.
The severity of this roughness mirrors disease progression, making it useful for large-scale drug screens.
Sleep disturbance, another hallmark of HD, is also modeled well in flies. Sheeba Vasu’s lab and others developed a circadian model by expressing mutant Huntingtin genes in neurons that regulate daily rhythms. Like humans, flies show robust sleep-wake cycles, but these rhythms collapse with neurodegeneration. The timing of this breakdown depends on the number of polyQ repeats: with 50 repeats, flies lose rhythmicity about two weeks into adulthood; with 93, they lose it within two days.
Motor disturbances can also be measured easily. “For instance, we measure the time taken to cover a certain distance. Invariably, flies with the defective copy of Huntingtin are slower than those that express the normal copy,” Dr. Prakash said.
Using this system, Subramaniam Ganesh and Deepashree Sheshadri at IIT-Kanpur showed that glycogen synthase, an enzyme that produces glycogen, plays a protective role.
“Increasing [its levels] significantly alleviates HD phenotypes in fruit flies, improving survival, locomotion, neuronal integrity, and key molecular markers,” said Mr. Ganesh.
Still, researchers stress that findings in flies are only the first step. “The potential of glycogen modulation as a safe, effective treatment remains unproven, but the fly model lets us rapidly test [glycogen synthase’s] activators before moving to mammalian models,” Ms. Sheshadri said.
Dance as therapy
Beyond the laboratory, however, researchers are exploring more ways to ease symptoms and improve quality of life. Multiple studies have shown that structured movement through dance forms like the Argentine tango have helped patients with Parkinson’s disease regain some motor control.
Two studies suggest dance may help HD patients manage movement disturbances. A 2013 study published in Clinical Rehabilitation tested the video game ‘Dance Dance Revolution’, where players match dance steps to on-screen prompts. After six weeks of 45-minute sessions twice a week, patients showed better gait and balance compared to when they played a hand-held video game.
Another study in 2019 in Journal of Huntington’s Disease offered contemporary dance classes at least once a week for five months. Participants who attended dance classes showed better movement scores, verbal fluency, and mood than those receiving standard care. Patients in this study even expressed a desire to continue dancing after the trial ended.
While these results are promising, larger studies are required to confirm whether dance therapy can reliably reduce HD symptoms.
Nevertheless, doctors are cautiously optimistic.
“Dance, music therapies, and any type of relaxation of mind and body have good responses. We encourage this for management of HD and other movement disorders,” Dr. Kukkle said.
At the conference, dancer and teacher Daksha Mashruwala proposed Odissi as a choreographic therapy for HD patients. With guidance from a physiotherapist, she has designed a programme that uses controlled movements of Odissi mudras and the stable chauka stance to help patients counter uncontrolled movements. Weighted waistbands and anklets can aid trunk mobility, gait, and hand control.
“Our goal is for Odissi to complement conventional treatment, while also offering patients a way to engage socially with other learners,” she said, pointing to the potential of dance not just for motor benefits but also for social interactions.
Yet even as science and therapy advance, patients and their families face deeper challenges.
“What we need is a patient registry, which will help patients enroll in clinical trials, expand doctor networks, and raise awareness about HD,” Ms. Sheeba said.
But despite more than 200 families linked through a WhatsApp group, few have committed to formal registration. Concerns over anonymity and the heavy social stigma surrounding HD remain major barriers — not only to building a registry but to improving patients’ everyday lives.
Sheetal Potdar has a PhD in neuroscience and works as a science writer.
