Synosia Therapeutics today announced the start of a proof-of-concept clinical trial to evaluate the efficacy and safety of nitisinone (SYN-118), a potent and selective inhibitor of hydroxyphenylpyruvate dioxygenase (HPPD), as a treatment for Restless Legs Syndrome (RLS), a neurological disorder.

The trial is a randomised, double-blind, placebo-controlled study in patients with moderate to severe symptoms of RLS being conducted in two highly experienced European centres, the Somni Bene Institute for Medical Research and Sleep Medicine in Schwerin, Germany and the University Hospital for Neurology in Innsbruck, Austria. Results will be assessed using objective motor signs such as periodic limb movements and subjective severity ratings scales.

This is Synosia's second proof-of-concept trial using nitisinone, which is already under investigation for the treatment of Parkinson's disease. Nitisinone inhibits the enzyme HPPD from breaking down tyrosine, the precursor of the neurotransmitter dopamine, resulting in persistent elevation of plasma tyrosine. This innovative, first-in-class mode of action is expected to produce stable increases in brain dopamine levels and therefore offers an attractive alternative to current dopaminergic therapies for RLS. Current therapies are limited by the short-half life of available drugs, their dose-limiting side-effects, and the risk of developing "augmentation", a term used when RLS symptoms increase during treatment, which may require change of medication.

Synosia's Chief Executive Officer and President Ian Massey said: "We are encouraged based on our work in Parkinson's disease that nitisinone has the potential to be a once-daily treatment that could treat restless legs syndrome as efficiently as L-dopa or the dopamine agonists, but without the unpleasant side effects such as nausea, the need to uptitrate the dose to avoid dose-limiting intolerability, or the risk of developing augmentation."

Professor Birgit Högl, Coordinating Investigator at the Department of Neurology, Innsbruck Medical University, Austria added: "Nitisinone increases tyrosine concentrations, which has been shown in pre-clinical studies to increase dopamine turnover in the brain. We hope this will turn out to be an innovative treatment strategy for patients with this debilitating condition."

"Most of the recently published large-scale trials use the International RLS Study Group Rating Scale, an instrument with which RLS patients subjectively evaluate the severity of their symptoms," commented Dr Heike Beneš, Coordinating Investigator at The Institute for Medical Research and Sleep Medicine in Germany. "However, this exploratory study will also use a smart, efficient and data-rich approach: it will include sleep laboratory evaluation to assess sleep and periodic limb movements, known to be abnormal in subjects with RLS. Sleep laboratory evaluation has been demonstrated to be predictive of efficacy of medications used to treat RLS."

RLS is one of the most common, yet under-diagnosed, neurological disorders, which in its more severe forms affects an estimated 2.5% of the population in the US and Europe and can cause symptoms that impact on the quality of life of an even broader 6 to 11% of the general population 1,2,3,4,5. A chronic disease, RLS is most frequently diagnosed in patients of middle to older age. Symptoms include the urge to move the legs, usually accompanied by an unpleasant sensation, which worsens during periods of rest or inactivity. RLS can lead to severe sleep disruption and result in daytime sleepiness and a significant impairment of quality of life.

About Nitisinone

Nitisinone was discovered and developed by Syngenta, which has granted licensing rights to Swedish Orphan International (SOI) for orphan indications. SOI markets nitisinone in Europe and the United States for the treatment of hereditary tyrosinemia type 1, under the brand name Orfadin®. The development programme of SOI and Synosia for nitisinone has generated over 5,000 patient-years of clinical and market experience to date. In 2007, Synosia obtained rights from Syngenta to develop and commercialise nitisinone in all non-orphan indications.

About Synosia Therapeutics

Synosia Therapeutics develops and intends to commercialize innovative and clinically differentiated products for unmet medical needs in psychiatry and neurology. The privately-owned company has six clinical-stage compounds in its pipeline, acquired through key partnerships with Novartis, Roche and Syngenta. Synosia's pipeline includes two marketed drugs that will be tested in new indications, extending their reach into neurological and psychiatric diseases with high unmet medical need, including anxiety and Parkinson's Disease. Synosia's headquarters is in Basel, Switzerland.


This communication expressly or implicitly contains certain forward-looking statements concerning Synosia Therapeutics and its business. Such statements involve certain known and unknown risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of Synosia Therapeutics to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements.

Synosia Therapeutics is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.


1. Berger K. And Kurth T. RLS Epidemiology - frequencies, Risk Factors and Methods in population Studies. Movement Disorders (2007):22: S420-S423

2. Hening et al. The REST Study in Primary Care. Sleep Med. (2004):5:237-246.

3. Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest (2006). 130 (5): 1596-604.

4. Allen R. Walters A. et al. Restless legs syndrome prevalence and impact: REST general population study. Arch. Intern. Med. (2005):165(11):1286-92.

5. Wenning GK. Kiechl S. Et al. Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study. (2005) Lancet Neurol 4 (12): 815-20.

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