emrusolmin (TEV- '286) News

|||||||||| emrusolmin (TEV- '286) / MODAG, Teva
TOPAS-MSA: Targeting Oligomer Pathology of Alpha-Synuclein - A Study Evaluating the Safety and Efficacy of Emrusolmin in Patients with Multiple System Atrophy (Poster Hall (Exhibit Hall A)) - Aug 9, 2024 - Abstract #MDSCongress2024MDS_Congress_265;

|||||||||| emrusolmin (TEV- '286) / MODAG, Teva
Journal, Metastases: Interfering with aggregated ?-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins. (Pubmed Central) - Jul 1, 2024
We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized ?-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses.

|||||||||| emrusolmin (TEV- '286) / MODAG, Teva
Development of Positron Emission Tomography Agent for Alpha-Synuclein Imaging (Exhibit Hall D - Science Pavilion (Convention Center); Screen 14; In-Person Only) - May 8, 2024 - Abstract #SNMMI2024SNMMI_1165;
A series of novel ligands based on the structure-activity relationship of carbazole, imidazolopyridine and imidazolopyrimidine were designed, and in silico docking studies were performed to obtain binding affinity of novel alpha-synuclein ligands. Based on ADME and in vitro assays, the lead ligand [11C]ASRN37 was radiolabeled and exhbited higher BBB penetration in mice.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal: Molecular docking analysis of ?-Synuclein aggregation with Anle138b. (Pubmed Central) - May 7, 2024
Protein-protein docking showed that Anle138b interferes with ?-synuclein decamer formation. These results highlight the oligomer-directed inhibitory mechanism of Anle138b, without hindering the monomeric forms and provide molecular insights to advance its therapeutic development for Parkinson's and related synucleinopathies.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal: Anti-prion drugs do not improve survival in novel knock-in models of inherited prion disease. (Pubmed Central) - Apr 5, 2024
Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions, as well as anti-prion strategies that are not strain-dependent.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal: Discovery of small molecule benzothiazole and indole derivatives tackling tau 2N4R and ?-synuclein fibrils. (Pubmed Central) - Feb 19, 2024
Here, we rationally designed and synthesized benzothiazole- and indole-based compounds using the structural hybridization strategy between the benzothiazole N744 cyanine dye and the diphenyl pyrazole Anle138b that showed anti-aggregation activity towards 2N4R tau and ?-syn, respectively...Moreover, compound 48 remarkably inhibited ?-syn inclusion and cell confluence using M17D cells. Collectively, compounds 46 and 48 could serve as a basic structure for further optimization to develop clinically active AD and PD disease-modifying agents.

|||||||||| Review, Journal: Insights into the management of Lewy body dementia: a scoping review. (Pubmed Central) - Feb 9, 2024
Together with that, levodopa, antipsychotics, armodafinil, piracetam, and traditional medications like yokukansan were also used, when indicated...Talking about recent advances in the treatment of LBD, various disease-modifying therapies like ambroxol, neflamapimod, irsenontrine, nilotinib, bosutinib, vodobatinib, clenbuterol, terazosin, elayta, fosgonimeton, and anle138b are emerging out...With the different pharmacological and nonpharmacological modalities we have for treatment of LBD, all of them offer symptomatic relief only. Being a degenerative disease, definite cure of the disease can only be possible with regenerative measures.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Anle138b-P1-02: A randomised, double-blinded, placebo-controlled phase 1b study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of the oligomer modulator anle138b () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1422;
P1
Exposures were reached above the minimally effective plasma levels seen in animal models. Efficacy trials in patients with synucleinopathies are planned.

|||||||||| Review, Journal: Lewy Body Dementia: An Overview of Promising Therapeutics. (Pubmed Central) - Aug 12, 2023
Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal, Machine learning: Probing the molecular mechanisms of ?-synuclein inhibitors unveils promising natural candidates through machine-learning QSAR, pharmacophore modeling, and molecular dynamics simulations. (Pubmed Central) - Jul 18, 2023
Finally, molecular dynamics simulations demonstrated the superior stability of LTS0078917 compared to the clinical candidate, Anle138b...Our dynamic analysis of the inhibitor-monomer complex revealed a tendency towards a more compact conformation, potentially reducing the likelihood of adopting an elongated structure that favors the formation and aggregation of pathological oligomers. These findings offer valuable insights for the development of novel ?-synuclein inhibitors derived from natural sources.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Preclinical, Journal: Endogenous Amyloid-formed Ca-permeable Channels in Aged 3xTg AD Mice. (Pubmed Central) - Jun 25, 2023
These spontaneous Ca oscillations are sensitive to extracellular Ca, ZnCl, and the A? channel blocker Anle138b, suggesting that these spontaneous Ca oscillations in aged 3xTg AD mice are mediated by endogenous A?-formed channels.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal: Synthesis and Preliminary Characterization of Putative Anle138b-Centered PROTACs against ?-Synuclein Aggregation. (Pubmed Central) - May 27, 2023
Native and seeded ?Syn aggregation was determined with a new biosensor, and a partial correlation between ?Syn aggregation, cellular dysfunctions, and neuronal survival was obtained. Anle138b-PROTAC 8a was characterized as the most promising ?Syn aggregation inhibitor/degradation inducer, with potential usefulness against synucleinopathies and cancer.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Journal: Anle138b interaction in ?-synuclein aggregates by dynamic nuclear polarization NMR. (Pubmed Central) - May 22, 2023
The small central pyrazole moiety of anle138b is detected in close proximity to the protein backbone and differences in the contacts between fibrils and early intermediates are observed. For intermediate species, the 100 K condition for DNP helps to preserve the aggregation state, while for both fibrils and oligomers, the DNP enhancement is essential to obtain sufficient sensitivity.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Trial completion:  A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b) (clinicaltrials.gov) -  Mar 23, 2023
P1, N=54, Completed,  Sponsor: MODAG GmbH
For intermediate species, the 100 K condition for DNP helps to preserve the aggregation state, while for both fibrils and oligomers, the DNP enhancement is essential to obtain sufficient sensitivity. Active, not recruiting --> Completed

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Trial completion, Trial completion date, Trial primary completion date:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Mar 22, 2023
P1, N=70, Completed,  Sponsor: MODAG GmbH
Active, not recruiting --> Completed Active, not recruiting --> Completed | Trial completion date: Jun 2023 --> Dec 2022 | Trial primary completion date: Jun 2023 --> Nov 2022

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Trial completion date, Trial primary completion date:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Mar 20, 2023
P1, N=72, Active, not recruiting,  Sponsor: MODAG GmbH
Active, not recruiting --> Completed | Trial completion date: Jun 2023 --> Dec 2022 | Trial primary completion date: Jun 2023 --> Nov 2022 Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Jun 2023

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
Preclinical, Journal: Therapeutic Trial of anle138b in Mouse Models of Genetic Prion Disease. (Pubmed Central) - Mar 2, 2023
In the genetic models, however, the animals never reached a clear, measurable point of disease onset. We conclude that not all prion disease animal models are ideally suited to drug efficacy studies, and well-defined, quantitative disease metrics should be a priority.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment closed:  A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b) (clinicaltrials.gov) -  Jan 31, 2023
P1, N=54, Active, not recruiting,  Sponsor: MODAG GmbH
We conclude that not all prion disease animal models are ideally suited to drug efficacy studies, and well-defined, quantitative disease metrics should be a priority. Recruiting --> Active, not recruiting

|||||||||| TEV-56286 / MODAG, Teva
Journal: In Silico Study of the Interactions of Anle138b Isomer, an Inhibitor of Amyloid Aggregation, with Partner Proteins. (Pubmed Central) - Dec 24, 2022
Using flexible and cascaded molecular docking techniques, we aimed to expand our understanding of the molecular architecture of the protein complex between alpha-synuclein, cyclophilin A and the Anle138b isomer ligand. We demonstrated the possibility of intricate complex formation under cellular conditions and revealed that the main interactions that stabilize the complex are hydrophobic and involve hydrogen.

|||||||||| emrusolmin (TEV-56286) / MODAG, Teva
PET IMAGING OF ?SYN AGGREGATES IN A TRANSGENIC MOUSE MODEL OF PARKINSON (ONSITE - HALL G2) - Dec 23, 2022 - Abstract #ADPD2023ADPD_705;
Our autoradiography reveals the binding of anle138b to ?SYN aggregates, confirming its targeted binding. This demonstrates the potential of [11C]MODAG-005 as PET tracer for the future development of therapeutic compounds and to investigate response to therapies.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment closed:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Oct 12, 2022
P1, N=72, Active, not recruiting,  Sponsor: MODAG GmbH
This demonstrates the potential of [11C]MODAG-005 as PET tracer for the future development of therapeutic compounds and to investigate response to therapies. Recruiting --> Active, not recruiting

|||||||||| TEV-56286 / MODAG, Teva
Journal: The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils. (Pubmed Central) - Sep 20, 2022
Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well.

|||||||||| TEV-56286 / MODAG, Teva, Tasigna (nilotinib) / Novartis, Inhibikase
Preclinical, Journal: Removal of proteinase K resistant αSyn species does not correlate with cell survival in a virus vector-based Parkinson's disease mouse model. (Pubmed Central) - Sep 14, 2022
However, the KYP-2047 treatment that was initiated at the time of symptom onset, failed to protect the nigrostriatal dopaminergic neurons. Our results emphasize the importance of whole αSyn aggregation process in the pathology of PD and raise an important question about the forms of αSyn that are reasonable targets for PD drug therapy.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment open:  A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b) (clinicaltrials.gov) -  Sep 14, 2022
P1, N=56, Recruiting,  Sponsor: MODAG GmbH
Our results emphasize the importance of whole αSyn aggregation process in the pathology of PD and raise an important question about the forms of αSyn that are reasonable targets for PD drug therapy. Not yet recruiting --> Recruiting

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
New P1 trial:  A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b) (clinicaltrials.gov) -  Sep 8, 2022
P1, N=56, Not yet recruiting,  Sponsor: MODAG GmbH

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment change, Trial completion date, Trial primary completion date:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Aug 25, 2022
P1, N=72, Recruiting,  Sponsor: MODAG GmbH
Not yet recruiting --> Recruiting N=48 --> 72 | Trial completion date: Jun 2022 --> Dec 2022 | Trial primary completion date: Jun 2022 --> Dec 2022

|||||||||| anle138b / MODAG, Teva
P1 data, PK/PD data, Preclinical, Journal: Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial. (Pubmed Central) - Jun 15, 2022
P1
N=48 --> 72 | Trial completion date: Jun 2022 --> Dec 2022 | Trial primary completion date: Jun 2022 --> Dec 2022 The favourable safety and PK profile of anle138b in doses resulting in exposures above the fully effective plasma level in a mouse Parkinson model warrant further clinical trials in patients with synucleinopathies.

|||||||||| anle138b / MODAG, Teva
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF THE OLIGOMER MODULATOR ANLE138B: A FIRST-IN-HUMAN RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 1 TRIAL () - Mar 9, 2022 - Abstract #ADPD2022ADPD_1721;
P1
Anle138b was safe and well tolerated in doses resulting in exposure levels above those fully effective in a mouse Parkinson model. These findings warrant further clinical trials in patients with synucleinopathies.

|||||||||| anle138b / MODAG, Teva
Preclinical, Journal: Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie-infected mice. (Pubmed Central) - Dec 25, 2021
The results show that alternating regimens containing various combinations of Anle138b, IND24 and IND116135 reduce the incidence of combination drug resistance, but do not significantly increase long-term disease-free survival compared to monotherapy. Furthermore, the alternating regimens induced regional vacuolation profiles resembling those generated by a single component of the alternating regimen, suggesting the emergence of strain dominance.

|||||||||| anle138b / MODAG, Teva
SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF THE OLIGOMER MODULATOR ANLE138B IN PARKINSON´S DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 1B TRIAL (ONSITE: 112) - Dec 17, 2021 - Abstract #ADPD2022ADPD_284;
P1
Conclusions In patients with PD, anle138b was safe and well tolerated in doses resulting in exposures above the putatively effective plasma levels. These findings warrant long-term efficacy trials in patients with synucleinopathies.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment change, Trial completion date, Trial primary completion date:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Oct 26, 2021
P1, N=48, Recruiting,  Sponsor: MODAG GmbH
These findings warrant long-term efficacy trials in patients with synucleinopathies. N=24 --> 48 | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022

|||||||||| anle138b / MODAG
Clinical, Journal: Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance. (Pubmed Central) - Oct 2, 2021
PD03 and Anle138b can selectively target oligomeric α-synuclein, resulting in attenuation of neurodegeneration in the PLP-α-syn mice. Both approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies.

|||||||||| anle138b / MODAG, Comtan (entacapone) / Novartis, Orion Corp, trodulamine (MSI-1436) / Novo Biosci
Review, Journal: One ring is sufficient to inhibit α-synuclein aggregation. (Pubmed Central) - Aug 13, 2021
Here, we describe a subset of compounds containing a single aromatic ring, like dopamine, ZPDm, gallic acid, or entacapone, which act as molecular chaperones against α-synuclein aggregation...Moreover, some of these compounds can disentangle mature α-synuclein amyloid fibrils. Their simple structures allow structure-activity relationship analysis to elucidate the role of different functional groups in the inhibition of α-synuclein aggregation and fibril dismantling, making them informative lead scaffolds for the rational development of efficient drugs.

|||||||||| anle138b / MODAG
Journal: Novel furan-2-yl-1H-pyrazoles possess inhibitory activity against α-synuclein aggregation. (Pubmed Central) - Jun 22, 2021
The compounds were found to inhibit α-syn aggregation with efficacy comparable to the promising drug candidate anle138b. The results of this study indicate that compounds 8b, 8l and 9f may qualify as secondary leads for the structure-activity relationship studies aimed to identify the suitable compounds for improving the modulatory activity targeted at α-syn self-assembly related to Parkinson's disease.

|||||||||| [VIRTUAL] Experimental Therapies for Rare Movement Disorders – MSA (Room Vienna) - May 30, 2021 - Abstract #EAN2021EAN_1278;
P1, P2
In this regard, enhancing the clearance of α-synuclein via autophagy (transcription factor EB) or direct proteolysis (neurosin), inhibiting its aggregation (anle 138b and CLR01) or post-translational truncation (belnacasan), as well as active (Affitope PD01A) and passive immunotherapy (CD5-D5) have demonstrated beneficial effects on motor behavior, α-synuclein burden and other neuropathological readouts in transgenic MSA mice...These preclinical results have motivated the conduction of a phase I trial to evaluate the safety and tolerability of repeated administrations of specific active immunotherapy against α-synuclein with Affitope PD01A and PD03A (NCT02270489)...In this regard, a phase I trial to assess the safety and tolerability of anle138b in healthy volunteers is currently ongoing (NCT04208152). Additionally, a small phase II trial with exenatide (NCT04431713), an approved antidiabetic, is ongoing.

|||||||||| anle138b / MODAG
Journal: [C]MODAG-001-towards a PET tracer targeting α-synuclein aggregates. (Pubmed Central) - May 29, 2021
Additionally, a small phase II trial with exenatide (NCT04431713), an approved antidiabetic, is ongoing. MODAG-001 provides a promising lead structure for future compound development as it combines a high affinity and good selectivity in fibril-binding assays with suitable pharmacokinetics and biodistribution properties.

|||||||||| Previfenon (epigallocatechin gallate) / MELISA Institute, anle138b / MODAG
Journal: Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. (Pubmed Central) - Feb 10, 2021
We found that anle138b and fulvic acid decrease aSyn and tau aggregation, that epigallocatechin gallate decreases aSyn aggregation, and that dynasore reduces tau internalization. Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Enrollment open:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Jan 6, 2021
P1, N=24, Recruiting,  Sponsor: MODAG GmbH
Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions. Not yet recruiting --> Recruiting

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
New P1 trial:  A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of anle138b in Parkinson's Disease (clinicaltrials.gov) -  Dec 27, 2020
P1, N=24, Not yet recruiting,  Sponsor: MODAG GmbH

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
Trial completion:  A First-in-Human Study of Single and Multiple Doses of anle138b in Healthy Subjects (clinicaltrials.gov) -  Aug 7, 2020
P1, N=68, Completed,  Sponsor: MODAG GmbH
Not yet recruiting --> Recruiting Recruiting --> Completed

|||||||||| anle138b / MODAG
Clinical, Journal: Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. (Pubmed Central) - Aug 5, 2020
The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD.

|||||||||| memantine / Generic mfg.
Review, Journal: Harnessing ionic mechanisms to achieve disease modification in neurodegenerative disorders. (Pubmed Central) - Jul 22, 2020
In this view, mounting evidence points to ionic mechanisms (IMs) as targets with potential therapeutic efficacy across distinct NDD subtypes. The scope of this review is to present clinical and preclinical evidence supporting the link between disruption of IMs and neuronal death in specific NDDs and to critically revise past and ongoing attempts of harnessing IMs for the development of neuroprotective treatments.

|||||||||| anle138b / MODAG
Journal: Emergence of prions selectively resistant to combination drug therapy. (Pubmed Central) - Jul 22, 2020
Here, we tested the efficacy of combination therapy with two such drugs, IND24 and Anle138b, in scrapie-infected mice...To our knowledge, this is the first report of a pathogen with specific resistance to combination therapy despite being susceptible to monotherapy. Our findings also suggest that combination therapy may be a less effective strategy for treating prions than conventional pathogens.

|||||||||| anle138b / MODAG
Preclinical, Journal: Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau. (Pubmed Central) - Jul 18, 2020
Late-stage oligomer modulation effectively ameliorated tau pathology in hTau mice and rescued metabolic function. Molecular imaging by FDG-PET can serve for monitoring effects of Anle138b treatment.

|||||||||| anle138b / Modag
Journal: Anle138b prevents PrP plaque accumulation in Tg(PrP-A116V) mice but does not mitigate clinical disease. (Pubmed Central) - Feb 22, 2020
They also displayed greater reductions in insoluble and PK-resistant PrP than TgGSS mice. Although these results support an anti-aggregating effect of anle138b, the discordance in clinical efficacy noted between the two prion disease models tested underscores the pathophysiological differences between them and highlights the need to consider differences in susceptibilities among prion subtypes when assessing potential therapies for prion diseases.

|||||||||| anle138b / Modag
Modulation of aggregating proteins studied by NMR and beyond in neuro- and cellular degeneration (203B, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_10437;
Prevention of formation of these toxic oligomers by small molecules, specifically anle138b, observed in vitro and in vivo (3) using ultracentrifugation or superresolution imaging (4), specifically anle138b, leads to neuroprotection and restoration of functionality of the neurons in all mentioned diseases, specifically in PD (3,4), MSA (5), AD based on tau (6) or Abeta42 overexpression (7) and T2DM (8). Biophysical characterization of anle138b with target proteins will be discussed (6,9) in solution and in membranes with NMR spectroscopy.

|||||||||| anle138b / Modag
[VIRTUAL] THE DIPHENYL-PYRAZOLE ANLE138B INHIBITS TOXIC AMYLOID-BETA AND TAU CHANNELS IN MITOCHONDRIAL MEMBRANES (EXHIBITION HALL) - Jan 6, 2020 - Abstract #AATADPD2020AAT_ADPD_764;
Again, anle138b was shown to reduce the pore-like ionic currents across the lipid bilayer membranes. Conclusions Anle138b is a small-molecule compound that protects mitochondria from insult by amyloid-beta and tau aggregates, potentially by preventing formation of, or blocking ionic flux through, the amyloid channels.

|||||||||| anle138b / Modag
Preclinical, Journal: Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. (Pubmed Central) - Jan 4, 2020
Conclusions Anle138b is a small-molecule compound that protects mitochondria from insult by amyloid-beta and tau aggregates, potentially by preventing formation of, or blocking ionic flux through, the amyloid channels. Anle138b reduces α-synuclein accumulation in PLP-hαSyn mice, leading to neuroprotection, reduction of microglial activation, and preservation of motor function supporting the use of anle138b in a future clinical trial for MSA.

||||||||||  emrusolmin (TEV- '286) / MODAG, Teva
New P1 trial:  A First-in-Human Study of Single and Multiple Doses of anle138b in Healthy Subjects (clinicaltrials.gov) -  Dec 22, 2019
P1, N=92, Recruiting,  Sponsor: MODAG GmbH



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