Five latest advancements in Tourette’s syndrome research

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 the 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 syndrome. And new research has uncovered further links to brain circuits and Tourette’s. 

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. This year witnessed a prospective treatment on the horizon as well as cannabinoids being tested for central nervous system disorders like Tourette’s. Let us take a look at some recent advancements in Tourette’s syndrome research. 

Emalex’s ecopipam for Tourette syndrome: will this new drug in over 50 years bag approval? 

One of the biggest advancements in Tourette syndrome research this year has been the encouraging phase 3 results of ecopipam to better manage tics in patients. Developed by Emalex Biosciences, ecopipam is a dopamine antagonist, so it blocks the neurotransmitter and hormone dopamine that controls muscle movements in the brain. As tics are associated with an excess of dopamine, curbing its levels reduces both the severity and the frequency of tics.  

The promising phase 3 trial, which predominantly enroled children – 167 children and 49 adults – showed reductions in vocal and motor tics in those people who were given the drug for 12 weeks. Motor tics are body movements like eye blinking or shoulder shrugging whereas vocal tics involve sounds like humming, throat clearing, and repetitive sounds and utterances.  

However, 41.9% of children had their symptoms relapse when the dosage was prolonged to an additional 12 weeks compared to 68.1% of participants on placebo. This was viewed as a 50% loss of the benefit, according to the Yale Global Tic Severity Score, a measure that assesses the severity and frequency of symptoms of tic disorders like Tourette syndrome and obsessive-compulsive disorder in children aged between six and 17. Still, the primary endpoint, which was the time taken for children to relapse on ecopipam was met, ultimately regarded as a win. The most common side effects were drowsiness, insomnia, anxiety, fatigue, and headaches.  

These outcomes strengthen previous phase 2 study results where participants experienced a 30% decline in tic severity in 150 children with Tourette syndrome after 12 weeks back in 2023. Emboldened by the results, the Illinois-based biotech’s plans to submit the medicine for U.S. Food and Drug Administration (FDA) approval this year. If it does hit the market, it would be the first new medicine to treat Tourette syndrome in more than fifty years. 

PDE10A inhibitors: Noema and Eumentis’ candidate to battle it out in the clinic 

Shortly behind Emalex’s ecopipam but also on the radar is a fellow inhibitor drug. The Swiss company Noema Pharma’s gemlapodect, which it dubbed NOE-105, is a PDE10A inhibitor. It targets the enzyme PDE10A. This particular enzyme emerged as a therapeutic target recently as it has been linked to signaling that occurs in the basal ganglia, which is the part of the brain that control muscle movements. The goal is the same as that of ecopipam’s: to decrease the severity and frequency of tics.   

As it pushes through phase 2 studies at the moment, it reaped positive results a year ago when nearly 57% of patients who were treated with gemlapodect showed tic improvement and out of those who were on the target clinical dose range, 87.5% showed improvement. A statistically significant improvement of -7.8 points for all patients, and -12.8 points for patients was measured by the Yale Global Tics Severity Scale Total Tic Score at the target clinical dose. 

Meanwhile, California-based Eumentis Therapeutics has its own PDE10A inhibitor in the clinic as well. Currently in phase 2 studies, EM-221’s investigational new drug (IND) application was cleared by the FDA earlier this year. This was following preclinical trials that suggested that the drug, which is primarily being studied in people with schizophrenia, had an effect in rats with Tourette’s. It reduced tic-like movements and disrupted a phenomenon known as prepulse inhibition – when a weaker stimulus prevents a reaction to a stronger stimulus through a startle reflex – involved in Tourette syndrome.  

It will be a few years until we see which one beats the other and makes it to market first, but it will be interesting to know how things play out with the PDE10A inhibitors racing for approval. 

Research finds link between brain cell connectivity and Tourette’s: what does this mean for drug discovery? 

Currently approved drugs do more to manage symptoms in Tourette syndrome rather than address the root causes that have to do with dopamine production and brain circuits. And this is mainly because the exact cause of Tourette syndrome has not been identified barring the knowledge that they are linked to genetic and environmental factors. However, a new study has uncovered how brain cell changes impact the manifestation of Tourette syndrome. 

The research published in Mayo Clinic earlier this year found that people with Tourette syndrome have around half the number of brain cells that help calm hyperactive movement signals in the brain as people without the condition.    

The scientists began by analyzing more than 43,000 cells in the basal ganglia from brain tissues from people with and without Tourette after they had died. Having investigated how the genes in the cells were working, they looked into how changes in the brain’s gene mechanisms triggered stress and inflammation. This led to the discovery that people with Tourette syndrome had half the number of interneurons, which are nerve cells located in the central nervous system that connect other neurons to form complex circuits, compared to people without the condition.  

The scientists also found a close link between the spiny neurons that make up most of the cells in the basal ganglia and the brain’s immune cells known as the microglia involved in inflammation in Tourette syndrome. 

“We’re seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms,” said Yifan Wang, co-author of the study in a press release.   

With this newfound knowledge, they plan to study how these changes develop in the brain and lead to Tourette’s and what genetic factors play a role in all of it. 

Is deep brain stimulation the answer for people who don’t respond to other treatments? 

Meanwhile, deep brain stimulation (DBS) has paved the way for transformative treatment approaches for Parkinson’s disease. 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. The therapy has been picking up speed as a measure to treat Tourette’s syndrome.  

A recent research paper published in Nature saw that DBS was effective in patients with Tourette syndrome who did not respond well to other treatments. Scientists looked at a process known as thalamo-cortical oscillatory connectivity, which is basically neural activity between the thalamus, which relays sensory and motor signals to the cerebral cortex, and other parts of the brain.  

Employing Medtronic’s Percept PC neurostimulator, they identified a network connecting the different regions in the brain and the thalamus and that functional connectivity strength – the measure of how strongly the brain activity of two or more regions correlates – poorly impacted people with Tourette syndrome. 

Moreover, an earlier trial explored how closed-loop DBS 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. 

As the trial proved the therapy’s efficacy, it was also deemed safe and feasible, although participants faced side effects like headaches and anxiety.  

Wrist device for Tourette’s syndrome brings down tic severity 

Furthermore, to curtail the severity of tics, Neupulse has been regarded as a game-changing device for people with Tourette syndrome.  

It gained popularity after Scottish singer-songwriter Lewis Capaldi tested it out before a gig two years ago. The device was created by Neurotherapeutics, a U.K.-based company that targets neurological disorders, and is a spin-out of University of Nottingham.   

The participants of a study 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 will launch Neupulse in the U.K. in 2026 following a £2.5 million ($3.35 million) investment to propel R&D last year.