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Named after French neurologist Georges Gilles de la Tourette, who first described the disorder in 1885, Tourette’s syndrome is estimated to affect one in 10 to 1000 people worldwide. A neurological condition, the disorder causes involuntary movements and sounds, commonly known as tics. Although its exact cause isn’t known, research points to a link between the effect of the dysregulation of brain chemicals like dopamine and serotonin and Tourette’s syndrome. Despite it being regarded as a genetic condition, Tourette’s syndrome is influenced by environmental factors - like low birth weight and pregnancy complications - as well. While current treatments include medication that blocks dopamine, and behavioral therapy like habit reversal therapy (HRT) - where children and teens are trained to monitor their tics, and become aware of and overcome the urge to tic - there is a need for wider therapeutic approaches. As we observe Tourette’s Awareness Month from May 15 to June 15, let us take a look at some recent advancements in Tourette’s syndrome research. New diagnostic tool bolsters Tourette’s syndrome research Tourette’s can only be diagnosed - once other conditions are ruled out through scans like MRIs - if you’ve had several tics for a year. But now, a potentially transformative diagnosis tool could be able to diagnose the disease in a day. A study, which was led by Kevin Black, a professor of psychiatry at Washington University School of Medicine in the U.S., documented the occurrence of tics in 78 children for 1000 minutes over two sessions - a year apart from each other. Black then sought out the expertise of Rajan Chakrabarty, an aerosol scientist who specializes in the study of chaos and patterns in complex environmental systems. Based on the understanding that chaos is not random - and in fact, it could even follow a pattern - the timing of Tourette’s tics was measured using a means to quantify chaos, called fractal dimension. According to Black’s data from the study, although the data gathered seemed like it was part of a chaotic system, tic data strayed from the chaotic system, through which the fractal dimension value was calculated. The figures were validated when they observed that when the tic score went up, the fractal dimension had fallen, making the two factors inversely related to each other. Yet to be investigated further, this could prove constructive for a doctor who will be able to measure the duration of the tics in a patient who might even be visiting for the first time, and determine Tourette’s as the cause of it. As a result, treatment measures could be implemented sooner, not only for patients who will be diagnosed with Tourette’s, but also for others who will be able to eliminate the cause of their tics as stemming from Tourette’s. Wrist device brings down tic severity Some people who have been diagnosed with Tourette’s syndrome experience moderate to severe tics. In the U.S., that’s about 44% of the total reported cases. To curtail the severity, a recent clinical trial has found that a device designed to aid in managing Tourette’s symptoms reduces the frequency of tics. The device Neupulse, which has gained popularity after Scottish singer-songwriter Lewis Capaldi tested it out before a gig, was created by Neurotherapeutics Ltd, a U.K.-based company that targets neurological disorders, and is a spin-out of University of Nottingham. The participants of the research had to wear the device at home at the same time every day for 15 minutes, for the duration of a month. By delivering electrical pulses in order to lower the number of tics, the electric band was successful in bringing about a reduction in tic severity by 35%, and 59% out of 121 participants saw their tics brought down by at least 25% compared to baseline. The mechanism of Neupulse is based on an earlier study that investigated the effect of repetitive trains of electrical stimulation to the median nerve - which helps in the movement of the forearm, wrist, hand and fingers - to elicit rhythmic electrical activity in the brain. It was discovered that this decreased tic frequency and intensity, and even put an end to the urge-to-tic for people with Tourette’s. With the success of the prototype, the company is looking to develop the product for it to be made commercially available to people with Tourette’s syndrome. New drug sees promising outcome in phase 2b trials for Tourette’s syndrome An investigational drug candidate has proven its efficacy for the treatment of Tourette’s syndrome in a research conducted by the U.S.-based Emalex Biosciences. Results of the trial which were published in the journal Pediatrics demonstrated that the candidate ecopipam was able to significantly bring down the tic score - a 30% reduction from baseline - in participants after 12 weeks. The randomized, placebo-controlled phase 2b trial enrolled subjects aged between six and 18 with a baseline Yale Global Tic Severity Score (YGTSS) - a commonly used tool to quantify the severity of tic symptoms - of or more than 20 (total tic score). As the super-sensitivity of one of the receptors of dopamine - a neurotransmitter in the central nervous system (CNS) - D1 may be associated with Tourette’s, ecopipam works by blocking dopamine at D1 in order to target symptoms. While participants did not experience adverse effects to ecopipam, the most frequent ones were headache, insomnia, fatigue and somnolence - a state of drowsiness associated with sleeping disorders. To advance in phase 3 clinical trials, as well as for the potential commercialization of the drug candidate, the company secured $250 million in a series D funding round last year. Closed-loop deep brain stimulation shows encouraging results as Tourette’s therapy Deep brain stimulation (DBS) has paved the way for transformative treatment approaches for Parkinson’s disease. Moreover, the therapy has been picking up speed as a measure to treat Tourette’s syndrome. And a recent trial suggests that closed-loop deep brain stimulation might be effective in tackling the disease. The study carried out by neuroscientists at the University of Florida in the U.S. demonstrated a reduction of at least 40% in the YGTSS score at six months after receiving the treatment. The trial observed four participants with Tourette’s syndrome above the age of 21. DBS involves the implantation of electrodes in certain regions of the brain where electrical impulses are produced and then regulated - by a pacemaker-like device - to modulate communication in the brain. But unlike the traditional method, closed-loop DBS benefits from delivering impulses according to when symptoms are present, thus cutting down on the amount of energy required, and as a result, could potentially minimize side effects. As the trial proved the therapy’s efficacy, it was also deemed safe and feasible, although participants faced side effects like headaches and anxiety. New cannabinoid-based drug to begin clinical trials soon The Israeli-based biopharma Scisparc Ltd. has successfully completed the production of its drug candidate SCI-110 and will soon begin clinical trials for the treatment of Tourette’s syndrome, as of March 2023. SCI-110 contains dronabinol - a synthetic form of tetrahydrocannabinol (THC) - which was approved by the FDA to treat HIV/AIDs-induced anorexia and side effects to chemotherapy such as nausea and vomiting, nearly three decades ago. Now, growing research suggests that the compound could even target tic symptoms in Tourette’s patients. The drug candidate applies a mechanism where it stimulates the cannabinoid receptors in the CNS to improve the uptake of THC into the system. The therapy is set at a low dosage, implying lesser side effects upon ingestion. The upcoming phase 2b randomized, placebo-controlled study will examine the efficacy, safety and tolerability of the candidate for daily dosage in participants aged between 18 and 65. Assessing the tic severity change according to YGTSS at week 12 and 26, the company will also measure any adverse reactions to the drug. Looking ahead, the company will work with the FDA for a regulatory pathway to expedite potential commercialization.

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Five latest advancements in Tourette’s syndrome research

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