Neurolixis CEO, Adrian Newman-Tancredi, will present a lecture at the Central European Biomedical Congress as part of a session on treatment-resistant depression (details below). His lecture will focus on recent research on serotonergic 'biased agonists' targeting 5-HT1A receptors. In particular, novel compounds have been identified that target cortical 5-HT1A receptors to elicit neuronal responses, such as ERK phosphorylation and BDNF release, which are markers of antidepressant activity. In animal models, such biased agonists elicit antidepressant-like activity similar to that of ketamine, an effective antidepressant which, however, has substantial side-effects.  The new compounds raise the prospect of achieving robust antidepressant efficacy with superior tolerability.

Following the Congress, a manuscript summarizing the session will be published in British Journal of Pharmacology.

4th Central European Biomedical Congress (online): Cracow, Poland
Session 6: Perspectives for therapy of treatment-resistant depression, June 8, 2021

  • S.06-1 : Wiesław J. Cubala
    Medical University of Gdansk, Poland
    New developments in understanding mechanisms of drug resistance in the treatment of depression
  • S.06-2 : Łukasz Święcicki
    Institute of Psychiatry and Neurology, Warsaw, Poland
    Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS
  • S.06-3 : Paul Willner
    Swansea University, Swansea, UK
    Pharmacological and optogenetic studies on mechanisms of resistance to antidepressant drugs in animal models of treatment-resistant depression
  • S.06-4 : Adrian Newman-Tancredi
    Neurolixis, Castres, France
    Cortical 5-HT1A receptor biased agonism – a novel mechanism for effective therapy of treatment-resistant depression

NLX-112, a serotonin 5-HT1A receptor agonist developed by Neurolixis, reversed motor deficits in a transgenic model of Spinocerebellar ataxia3 (SCA3), a rare genetic orphan disease. The team led by Prof. Patricia Maciel, at the University of Minho, Portugal, reported online in the journal, Neurobiology of Disease, that NLX-112 restored motor function in nematode worms that express the same gene mutation as that seen in SCA3 patients.

Prof. Maciel commented: “SCA3, also known as Machado-Joseph disease, is an inherited condition. Symptoms including clumsiness, loss of strength, and tremor in the arms and legs that worsen over time, eventually leading to very severe disability. Our new data suggest that NLX-112 may improve the condition of patients suffering from this debilitating disorder .”

Neurolixis is now collaborating with Prof. Maciel’s team to test NLX-112 in transgenic SCA3 mice. The project, supported by the US Dept. of Defense, will determine whether extended NLX-112 administration attenuates SCA3 symptoms and slows down their development.

Adrian Newman-Tancredi, CEO of Neurolixis commented: “SCA3 is incurable and there is no approved treatment. If the results seen in the transgenic nematode worm model are translated to transgenic SCA3 mice, Neurolixis will seek to develop NLX-112 in clinical trials for SCA3 patients. NLX-112 has previously been tested in over 500 patients for other indications so we know it is safe and well tolerated. ”

NLX-112 is currently undergoing a Phase 2A clinical trial for treatment of L-DOPA-induced dyskinesia in Parkinson’s disease patients and the new SCA3 data suggests that it may also have utility for treatment of additional movement disorders.

See Full publication – Open Access:
Identification of the 5-HT1A serotonin receptor as a novel therapeutic target in a C. elegans model of Machado-Joseph disease.
Pereira-Sousa et al., Neurobiology of Disease, 28 Jan 2021 (Online ahead of print) doi: 10.1016/j.nbd.2021.105278, PMID: 33516872

Leading charities Parkinson’s UK and The Michael J. Fox Foundation for Parkinson’s Research (MJFF) have joined forces with Neurolixis to fund a $2 million Phase 2A trial investigating the clinical effects of NLX-112. The compound has previously shown robust capacity for reducing uncontrolled movements, known as dyskinesia. Dyskinesia is experienced by people with Parkinson's disease who have been treated for several years with levodopa - a standard treatment for Parkinson’s. Between 40 and 50 percent of people with Parkinson’s will experience dyskinesia after just five years of taking levodopa.

NLX-112 works by targeting brain neurons that produce serotonin. These neurons are believed to contribute to the development of dyskinesia by converting levodopa - the main drug taken for Parkinson’s - into dopamine and releasing it in an erratic manner. NLX-112 stabilizes the amount of dopamine these serotonin cells release.

The new study, led by a team at the Karolinska Institute in Sweden, will now assess whether NLX-112 is safe and well-tolerated in people with Parkinson's. The study will also investigate whether NLX-112 can reduce dyskinesia as well as some non-motor symptoms, such as depressed mood and disturbed sleep.

See the full press release.

Neurolixis Inc. is delighted to announce the appointment of Dr. Christopher Jankosky, MD, MPH, as a member of its Advisory Board

Dr. Jankosky' career as a neurologist and occupational medicine expert in the U.S. Navy, together with his work in the FDA have given him a profound understanding of both CNS disorders and regulatory aspects of drug develoment. Dr. Jankosky's broad experience as a corporate medical advisor will provide valuable insights and facilitate the advancement of the Neurolixis programs.

See more information concerning Neurolixis' team here.

Neurolixis Inc. offers a warm welcome to Fabienne Herbrecht, as Director of Clinical Development.
Dr. Herbrecht has gained extensive experience of drug development at a clinical level in several large and medium-sized pharmaceutical companies where she managed development, regulatory and clinical programs on drug candidates. Her expertise will be valuable as Neurolixis moves forward with development of its drug pipeline, notably as concerns targeting Parkinson's disease with the Phase 2A clinical candidate, NLX-112.

See more information concerning Neurolixis' management team here.


A drug discovery program run by Neurolixis in collaboration with researchers at Jagiellonian University (Krakow, Poland) has identified the first selective serotonin 5 HT1A receptor 'biased agonists' targeting beta-arrestin activation. Serotonin (5-hydroxytryptamine, 5-HT) is a key brain neurotransmitter that acts by activating neuronal receptors such as 5-HT1A. Neurolixis has developed a platform of novel compounds, known as ‘biased agonists’ that preferentially target specific intracellular signaling cascades via 5-HT1A receptors. The new study, reported in the Journal of Medicinal Chemistry, describes novel biased agonists that very selectively and potently activate beta-arrestin, a signaling mechanism at 5-HT1A receptors that is different to that targeted by previous Neurolixis biased agonists that target ERK1/2 phosphorylation. Notably, the beta-arrestin biased agonists exhibited distinct effects in rodent behavioral tests, likely reflecting specific neuronal signaling properties. The discovery may to lead to a new generation of molecules that differentially modulate this important neuronal receptor.

Adrian Newman-Tancredi CEO of Neurolixis commented, “We are excited that our drug discovery program has generated innovative compounds that could be relevant for treatment of central nervous system disorders such as depression or chronic pain.”

See the full publication (open access):
Discovery of novel pERK1/2- or β-Arrestin-Preferring 5-HT1A Receptor Biased Agonists: Diversified Therapeutic-Like vs. Side Effects Profile.
Sniecikowska et al., J Med Chem. 2020 Sep 4. doi: 10.1021/acs.jmedchem.0c00814. PMID: 32883072


A new publication on NLX-112 further highlights its potential utility for treatment of dyskinesia (uncontrolled movements), a disturbing side effect of L-DOPA therapy in Parkinson's disease. NLX-112 was tested in parkinsonian macaques, a primate species that is highly predictive of response in human Parkinson's disease patients. When the macaques received NLX-112, their dyskinesia symptoms were  strongly reduced, confirming a previous study carried out in parkinsonian marmosets. Notably, NLX-112 did not interfere with the therapeutic movement facilitation produced by L-DOPA. Taken together, these results provide compelling support for testing NLX-112 in  Parkinson's disease patients. Safe and efficacious treatment of dyskinesia constitutes a clear medical need and NLX-112 could significantly improve the quality of life of Parkinson's disease patients. 

Full publication:  Depoortère et al. Parkinsonism and Related Disorders, vol. 78, p151-157, 2020

The Craig H. Nielsen Foundation, a private institution dedicated to supporting scientific research and improve the quality of life of those affected spinal cord injury, has awarded a $ 641,000 grant to investigate the capacity of NLX-112, a clinical-phase compound developed by Neurolixis, to restore bladder function in rodent models of spinal cord injury. Experiments will be carried out by a research team at Cleveland Clinic, Ohio, led Dr. Yu-Shang Lee.

Dr Lee commented “There are about 17,700 new cases of spinal cord injury in the US each year and over 250,000 new cases worldwide. Many complications arise from such injury, including lower urinary tract dysfunction with bladder over activity and poor voiding efficiency. These complications have significant negative impact on the quality of life of patients and there is a high medical need for effective treatments.”

Adrian Newman-Tancredi, PhD, DSc, CEO of Neurolixis, commented: “Previous studies conducted by Neurolixis have shown that NLX-112 has pronounced influence on spinal cord responses, including expression of biological markers and analgesic activity. These data suggest that NLX-112 has a mechanism of action that can attenuate spinal cord injury-induced urinary tract dysfunction.”

In addition to testing the effects of NLX-112, Dr. Lee will also investigate potential synergy of NLX-112 in combination with exercise training. If successful, such treatment strategies could be translated into a clinical setting by testing NLX-112 in patients with spinal cord injury.

See the full description of the Craig Nielsen Foundation grant here.


Neurolixis offers a warm welcome to Mark S. Kleven, PhD, as Director of Operations.

Dr. Kleven has gained extensive experience in several biotech and pharmaceutical companies where he managed in vivo pharmacology programs, prepared FDA-compliant regulatory documents and interacted with funding agencies including NIH and Dept of Defense. His project management expertise will be valuable as Neurolixis increases the scope of its programs in both the EU and the USA by developing clinical candidates targeting Parkinson's disease and Rett syndrome and also in characterizing development candidates from its proprietary drug discovery program.

See more information concerning Neurolixis' management team here.

A new study on NLX-112 tested its effects in marmosets with Parkinson’s-like symptoms. The marmosets had developed the side effect of dyskinesia in response to L-DOPA treatment, in a similar way to many people with Parkinson’s. The results showed that NLX-112 successfully reduced dyskinesia and, crucially, did not significantly reduce the effectiveness of L-DOPA, which many other similar drugs do. When NLX-112 was used on its own (without L-DOPA), it again improved movement problems. These promising results suggest that NLX-112 has potential as a future treatment for not only reducing dyskinesia, but also for improving the movement symptoms of Parkinson’s.

Adrian Newman-Tancredi, CEO of Neurolixis commented, “We are excited that NLX-112 has shown such positive results. If the striking preclinical data are reproduced in clinical trials, NLX-112 could significantly alleviate the troubling dyskinesia that prevent many Parkinson’s patients from performing routine daily tasks, thereby improving their quality of life.”

Full Press Release: Promising drug could treat Parkinson's
Full publication:  Neuropharmacology Vol. 167, 1 May 2020

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