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Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs

SIT161: A highly innovative approach to fight simultaneously the main underlying mechanisms in neurodegenerative diseases 
recognized by the scientific community

As the Western population ages, NDDs are becoming one of the most important epidemics of the 21st century and are supposed to double over the next 10-20 years. More than ever before, NDDs become a hot topic for pharmaceutical drug development.  
Despite the efforts of science and the tremendous amounts of money spent in NDD drug development, the FDA and EMA have only approved a few medical drugs in this field over the last decades, none of which can stop the progression of the diseases, but only manage the symptoms with a quite negative benefit/risk ratio. 
Patients frequently ask “Why does research take so long?”, “Why is progress so slow?” and “Why don’t we have effective therapies for these devastating diseases?”
Finally, increasing scientific data shows that the traditional NDD treatment approach was not adapted to the complex etiology and pathogenesis of neurodegenerative disease: 
The "one target one drug" approach of traditional drug conception, that has worked for decades in the successful development of pharmaceuticals, was unable to give satisfying answers to fight the complex mechanisms that cause NDDs. In addition to the "one target one drug" approach, the focused target areas, especially in AD with the “amyloid hypothesis",  are questioned today.    
It has been shown that various neurodegenerative diseases and even psychiatric disorders have a large extent of similarity in terms of neurological dysfunction and pathogenesis. 
Increasing scientific data suggest that to fight NDDs with efficacy, the combination of several main underlying mechanisms responsible in the complex pathogenesis of NDDs have to be taken into account.
This leads to the conclusion that there is an urgent need for the development of non-toxic molecules with neuroprotective disease-modifying action, capable to treat and prevent a combination of these underlying mechanisms simultaneously. 

Why the approach of SIT161 is different? 
Unique biopharmaceutical neuroprotective and neurorestorative effects  combined with  receptor selectivity and potency

Neurodegenerative diseases represent a large group of neurological disorders with heterogeneous clinical and pathological expressions, but, more and more studies demonstrate that NDDs have indeed a large extent of similarity in terms of neurological dysfunction and pathogenesis that have to be taken into account in order to fight NDDs with efficacy. 
As NDDs are chronic diseases, the developed molecules need to demonstrate an exceptional safety profile allowing long-term treatments. 
Our patented molecule targets simultaneously the main underlying mechanisms of NDDs and demonstrated significant efficacy in the treatment & the prevention of NDDs.
In neurodegenerative diseases, SIT 161 blocks UPR (unfolded protein response), neuroinflammation, ROS effects, apoptosis and maintain neuronal survival eliciting synaptogenesis and neurogenesis. 
In ALS models, SIT161 not only prevents protection of motoneurons, but it enhances cell survival. 
In AD models, SIT161 allowed to treat and prevent learning and memory deficits but also favors synergistic effect when used in combination with donepezil, ibuprofen or atorvastatin with dosage lowered by 3-4x. 
SIT161 showed a significant protective effect in other models among others in PD. 

SIT161: Its perfect safety profile

The compound has already been examined by regulatory bodies FDA and EMA and is approved for clinical studies in Europe and the US. 
It demonstrated a perfect safety profile in 1000+ subjects in various clinical trials including a Ph.2 clinical study in major depression without major side effect. 
The treatment of NDDs need very safe compounds for long-term medications and SIT161has demonstrated its safety profile for such a use. 


Next Steps towards SIT161 NDD clinical trials

Based on the promising pre-clinical data, SigmaThera targets to start clinical trials ALS and AD in 2020 while preparing CTA and performing additional pre-clinical data in 2019. 

Interested in licensing or investment?  

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References: 
  • Millan MJ, Agid Y, Brune M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ. et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11(2):141–168. doi: 10.1038/nrd3628. 
  • Kihoon Cha et al. Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data. BMC Med Inform Decis Mak. 2015; 15(Suppl 1): S7.
  • Cummings et al.; licensee BioMed Central Ltd. 2014: Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer's Research & Therapy 2014
  • Nino Goguadze, Elene Zhuravliova, Didier Morin, Davit Mikeladze, Tangui Maurice. Sigma-1 Receptor Agonists Induce Oxidative Stress inMitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress. Neurotoxicity Research. January 2019, Volume 35, Issue 1, pp 1–18
  • J. Wang et al. Sigma 1 receptor regulates the oxidative stress response in primary retinal Müller glial cells via NRF2 signaling and system  xc , the Na+ -independent glutamate–cystine exchanger. Free Radical Biology and Medicine 86 (2015) 25–36.
  • Tsung-Ping Su et al. Sigma-1 Receptor as a Pluripotent Modulator in the Living System. Trends Pharmacol Sci. 2016 April ; 37(4): 262–278. doi:10.1016/j.tips.2016.01.003
  • T. Hayashi* and T.-P. Su. The Sigma Receptor: Evolution of the Concept in Neuropsychopharmacology. Current Neuropharmacology, 2005, 3, 267-280
  • Weng et al. Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases. Journal of Biomedical Science (2017)
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