Five recent advances in Tourette’s syndrome research

Named after the 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 the exact cause is unknown, research suggests a link between the dysregulating effects of brain chemicals such as dopamine and serotonin and Tourette’s syndrome.

Although it’s considered a genetic condition, Tourette’s syndrome is affected by environmental factors — such as low birth weight and pregnancy complications — as well.

While current treatments include medication that blocks dopamine, and behavioral therapies such as habit reversal therapy (HRT) – in which children and adolescents are trained to monitor their tics, and become aware of and deal with urges for tics – there is a need for more therapeutic approaches. wide . As we observe Tourette Awareness Month from May 15 to June 15, let’s take a look at some of the latest advances in Tourette’s syndrome research.

Tourette’s can only be diagnosed – once other conditions have been ruled out through scans such as an MRI – if you have had multiple tics over the course of a year. But now, a potentially transformative diagnostic tool can diagnose disease in a day.

A study led by Kevin Black, a professor of psychiatry at Washington University School of Medicine in the US, documented the occurrence of tics in 78 children over 1000 minutes over two sessions – one year apart from each other. Black then sought 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 can even follow patterns – the timing of Tourette’s tics is measured using a tool for measuring chaos, called the fractal dimension.

According to Black’s data from the study, although the collected data appears to be part of a chaotic system, tic data deviates from a chaotic system, where fractal dimension values ​​are calculated. The numbers were validated when they observed that as the tic score went up, the fractal dimension had gone down, making the two factors inversely related to one another.

However upon further investigation, this could prove constructive for clinicians who will be able to measure the duration of tics in even perhaps first time patients, and determine Tourette’s as the cause. As a result, treatment measures can be implemented more quickly, not only for patients who will be diagnosed with Tourette’s, but also for other people who can eliminate the cause of their tics that have Tourette’s origin.

Wrist devices decrease the severity of tics

Some people who have been diagnosed with Tourette’s syndrome experience moderate to severe tics. In the US, it is about 44% of the total reported cases. To reduce severity, a recent clinical trial found that a device designed to help manage Tourette’s symptoms reduced the frequency of tics.

The Neupulse device, which gained popularity after Scottish singer-songwriter Lewis Capaldi tested it before a gig, is made by Neurotherapeutics Ltd, a UK-based company targeting nervous disorders, and is a spin-out of the University of Nottingham.

Study participants had to wear the device at home at the same time every day for 15 minutes, for a month. By sending electrical pulses to decrease the number of tics, the electrical tape was able to reduce the severity of the tics by 35%, and 59% of the 121 participants saw their tics decrease by at least 25% compared to baseline.

The Neupulse mechanism builds on previous studies investigating the effect of repetitive electrical stimulation circuits to the median nerve – which aids movement of the forearms, wrists, hands and fingers – to induce rhythmic electrical activity in the brain. It was found that the frequency and intensity of these tics decreased, and even ended urges for people with Tourette’s.

With the success of the prototype, the company is looking to develop a product to make it commercially available for people with Tourette’s syndrome.

The new drug is seeing promising results in a phase 2b trial

The studied drug candidate has proven its efficacy for the treatment of Tourette’s syndrome in a study conducted by US-based Emalex Biosciences.

Trial results published in journals Pediatrics demonstrated that the ecopipam candidate was able to significantly reduce tic scores – a 30% reduction from baseline – in participants after 12 weeks. The randomized, placebo-controlled Phase 2b trial enrolled subjects between the ages of six and 18 years with a baseline Yale Global Tic Severity Score (YGTSS) — a tool commonly used to measure the severity of tic symptoms — of or greater than 20 (total tic score).

As super-sensitivity of one of the dopamine receptors – a neurotransmitter in the central nervous system (CNS) – D1 can be attributed to Tourette’s, ecopipam works by blocking dopamine in D1 to target symptoms.

While participants did not experience any side effects from ecopipam, the most common ones were headache, insomnia, fatigue and drowsiness – a state of sleepiness associated with sleep disturbances.

To advance in phase 3 clinical trials, as well as for potential commercialization of drug candidates, the company secured $250 million in a series D funding round last year.

Closed-loop brain stimulation has shown encouraging results as a Tourette therapy

Deep brain stimulation (DBS) has paved the way for transformative treatment approaches for Parkinson’s disease. In addition, the therapy has gained pace as a treatment for Tourette’s syndrome. And recent trials have shown that closed-loop brain stimulation may be effective in treating the disease.

That Study conducted by neurologists at the University of Florida in the US showed a reduction of at least 40% in YGTSS scores at six months after receiving treatment. The trial looked at four participants with Tourette’s syndrome over the age of 21.

DBS involves implanting electrodes in specific areas of the brain where electrical impulses are produced and then regulated – by a pacemaker-like device – to modulate communication in the brain. But unlike traditional methods, closed-loop DBS benefits from symptomatic delivery of impulses, thereby reducing the amount of energy required, and as a result, potentially minimizing side effects.

As the trial proved the efficacy of the therapy, it was also deemed safe and feasible, although participants faced side effects such as headaches and anxiety.

A new cannabinoid-based drug will soon begin clinical trials

Biofarma Israel Scisparc Ltd. has successfully completed production of its drug candidate SCI-110 and will soon begin clinical trials for the treatment of Tourette’s syndrome, starting March 2023.

SCI-110 contains dronabinol – a synthetic form of tetrahydrocannabinol (THC) – which was approved by the FDA to treat anorexia due to HIV/AIDS and chemotherapy side effects such as nausea and vomiting, nearly three decades ago. Now, growing research suggests the compound may even target the tic symptoms in Tourette’s patients.

The drug candidate implements a mechanism that stimulates cannabinoid receptors in the CNS to increase THC uptake into the system. Therapy is administered at lower doses, implying less side effects after ingestion.

An upcoming phase 2b randomized placebo-controlled study will examine the candidate’s efficacy, safety, and tolerability for daily dosing in participants aged between 18 and 65 years. Assessing changes in tic severity according to YGTSS at 12 and 26 weeks, the company will also measure adverse reactions to the drug.

Going forward, the company will work closely with the FDA on regulatory pathways to accelerate potential commercialization.

New technologies related to Tourette’s research:

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