Delving into the Latest Updates on Neublastin with Synapse

Overview

Basic Info

Drug Type

Protein drugs

Synonyms

ARTN, Artemin, Enovin

+ [1]

Target

GDNF

Action

stimulants

Mechanism

GDNF stimulants(Glial cell line-derived neurotrophic factors stimulants)

Therapeutic Areas

Nervous System DiseasesSkin and Musculoskeletal DiseasesOther Diseases

Active Indication-

Inactive Indication

Intervertebral Disc DiseaseLumbar RadiculopathyNeuralgia+ [1]

Originator Organization

NsGene A/S

Active Organization-

Inactive Organization

NsGene A/S

Biogen, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 29872

The primary objective of the study is to assess the efficacy of Intravenous (IV) BG00010 (Neublastin) in improving pain in painful lumbar radiculopathy participants when administered 3 times per week for 1 week.
The secondary objectives of this study in this study population are as follows: To explore the duration of the effect of BG00010 in improving pain; To explore the dose response curve on pain reduction; To assess the safety and tolerability of BG00010; To assess the serum exposure to BG00010.

Start Date01 Jun 2013

Sponsor / Collaborator

Biogen, Inc.

NL-OMON40320

/ CompletedNot Applicable

Study of Safety, Tolerability, and Pharmacokinetics of BG00010 (Neublastin) Intravenous and Subcutaneous Single Ascending Doses in Healthy Volunteers, and Subcutaneous Multiple Ascending Doses in Subjects with Painful Lumbar Radiculopathy - SC and IV doses SAD/MAD study BG00010

Start Date15 Apr 2013

Sponsor / Collaborator

Biogen, Inc.

NCT01842126

/ CompletedPhase 1

Study of Safety, Tolerability, and Pharmacokinetics of BG00010 (Neublastin) Intravenous and Subcutaneous Single Ascending Doses in Healthy Volunteers, and Subcutaneous Multiple Ascending Doses in Subjects With Painful Lumbar Radiculopathy

The primary objective of the study is to evaluate the safety and tolerability of a range of single intravenous (IV) and subcutaneous (SC) doses of BG00010 in healthy volunteers, and a range of multiple SC doses of BG00010 in participants with painful lumbar radiculopathy. Secondary objectives of this study are to determine the single IV and SC dose pharmacokinetics (PK) profile of BG00010 in healthy volunteers including assessment of bioavailability by comparing SC exposure to IV exposure in each participant, to determine the multiple SC dose PK profiles of BG00010 in participants with painful lumbar radiculopathy, to assess the single IV and SC dose immunogenicity of BG00010 in healthy volunteers, to assess the multiple SC dose immunogenicity of BG00010 in participants with painful lumbar radiculopathy, and to assess the potential of BG00010 to reduce pain following multiple SC administrations in participants with painful lumbar radiculopathy.

Start Date01 Apr 2013

Sponsor / Collaborator

Biogen, Inc.

100 Clinical Results associated with Neublastin

Login to view more data

100 Translational Medicine associated with Neublastin

Login to view more data

100 Patents (Medical) associated with Neublastin

Login to view more data

182

Literatures (Medical) associated with Neublastin

01 Nov 2024·Cephalalgia

The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8

Article

Author: Yang, Chenyu ; McKemy, David D. ; Chen, Xunyang ; Alam, Sanaa ; Wei, Chao

Background Migraine has a strong genetic foundation, including both monogenic and polygenic types. The former are rare, with most migraine considered polygenic, supported by genome-wide association studies (GWAS) identifying numerous genetic variants linked with migraine risk. Surprisingly, some of the most common mutations are associated with transient receptor potential melastatin 8 (TRPM8), a non-selective cation channel that is the primary sensor of cold temperatures in cutaneous primary afferents of the somatosensory system. However, it is unlikely that the temperature sensitivity of TRPM8 is relevant in migraine-related tissues, such as the meninges, suggesting other activation mechanisms underly its role in migraine pathogenesis. Thus, to define the basis of the channel's involvement, we reasoned that cellular processes that increase cold sensitivity in the skin, such as the neurotrophic factor artemin, via its receptor glial cell-line derived neurotrophic factor family receptor alpha-3 (GFRα3), also mediate TRPM8-associated migraine-like pain in the meninges. Methods To investigate the role of artemin and GFRα3 in preclinical rodent migraine models, we infused nitroglycerin acutely and chronically, and measured changes in periorbital and hind paw mechanical sensitivity in male and female mice lacking GFRα3, after neutralization of free artemin with specific monoclonal antibodies, or by systemic treatment with a TRPM8-specific antagonist. Further, in mice lacking GFRα3 we tested the effects of supradural infusions of a mix of inflammatory mediators, as well as tested if dura stimulation with artemin or a TRPM8-specific agonist induce migraine-related pain in mice. Results We find that mechanical allodynia induced by systemic nitroglycerin, or supradural infusion of inflammatory mediators, involves GFRα3. In addition, neutralization of circulating artemin reduces the nitroglycerin phenotype, demonstrating the importance of this neurotrophic pathway in headaches. Further, we show TRPM8 expression in the meninges, and that direct supradural infusion of either a TRPM8-specific agonist or artemin itself produces mechanical allodynia, with the latter dependent on TRPM8 and ameliorated by concurrent treatment with sumatriptan. Conclusions These results indicate that neuroinflammatory events in the meninges can produce migraine-like pain in mice via artemin and GFRα3, likely acting upstream of TRPM8, providing a novel pathway that may contribute to headaches or migraine pathogenesis.

01 Aug 2024·Journal of Investigative Dermatology

The EGR1–Artemin Axis in Keratinocytes Enhances the Innervation of Epidermal Sensory Neurons during Skin Inflammation Induced by House Dust Mite Extract from Dermatophagoides farinae

Article

Author: Ou, Sukjin ; Lee, Young Han ; Ahn, Sung Shin ; Yeo, Hyunjin ; Koh, Dongsoo ; Lim, Yoongho ; Shin, Soon Young ; Yun, Sook Jung

Epidermal hyperinnervation is a critical feature of pruritus during skin inflammation. However, the mechanisms underlying epidermal hyperinnervation are unclear. This study investigates the role of the transcription factor EGR1 in epidermal innervation by utilizing wild-type (Egr1^+/+) and Egr1-null (Egr1^‒/‒) mice topically applied Dermatophagoides farinae extract from dust mite. Our findings revealed that Egr1^‒/‒ mice exhibited reduced scratching behaviors and decreased density of epidermal innervation compared with Egr1^+/+ mice. Furthermore, we identified artemin, a neurotrophic factor, as an EGR1 target responsible for Dermatophagoides farinae extract-induced hyperinnervation. It has been demonstrated that Dermatophagoides farinae extract stimulates toll-like receptors in keratinocytes. To elucidate the cellular mechanism, we stimulated keratinocytes with Pam3CSK4, a toll-like receptor 1/2 ligand. Pam3CSK4 triggered a toll-like receptor 1/2-mediated signaling cascade involving IRAK4, IκB kinase, MAPKs, ELK1, EGR1, and artemin, leading to increased neurite outgrowth and neuronal migration. In addition, increased expression of EGR1 and artemin was observed in the skin tissues of patients with atopic dermatitis. These findings highlight the significance of the EGR1-artemin axis in keratinocytes, promoting the process of epidermal innervation and suggesting it as a potential therapeutic target for alleviating itch and pain associated with house dust mite-induced skin inflammation.

01 Jul 2024·Journal of Autoimmunity

Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome

Article

Author: Lam, Grace ; Rosychuk, Rhonda J ; Bozorgmehr, Najmeh ; Redmond, Desiree ; Osman, Mohammed ; Elahi, Shokrollah ; Cohen Tervaert, Jan Willem ; Sligl, Wendy ; Shahbaz, Shima ; Saito, Suguru

A substantial number of patients recovering from acute SARS-CoV-2 infection present serious lingering symptoms, often referred to as long COVID (LC). However, a subset of these patients exhibits the most debilitating symptoms characterized by ongoing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). We specifically identified and studied ME/CFS patients from two independent LC cohorts, at least 12 months post the onset of acute disease, and compared them to the recovered group (R). ME/CFS patients had relatively increased neutrophils and monocytes but reduced lymphocytes. Selective T cell exhaustion with reduced naïve but increased terminal effector T cells was observed in these patients. LC was associated with elevated levels of plasma pro-inflammatory cytokines, chemokines, Galectin-9 (Gal-9), and artemin (ARTN). A defined threshold of Gal-9 and ARTN concentrations had a strong association with LC. The expansion of immunosuppressive CD71⁺ erythroid cells (CECs) was noted. These cells may modulate the immune response and contribute to increased ARTN concentration, which correlated with pain and cognitive impairment. Serology revealed an elevation in a variety of autoantibodies in LC. Intriguingly, we found that the frequency of 2B4⁺CD160⁺ and TIM3⁺CD160⁺ CD8⁺ T cells completely separated LC patients from the R group. Our further analyses using a multiple regression model revealed that the elevated frequency/levels of CD4 terminal effector, ARTN, CEC, Gal-9, CD8 terminal effector, and MCP1 but lower frequency/levels of TGF-β and MAIT cells can distinguish LC from the R group. Our findings provide a new paradigm in the pathogenesis of ME/CFS to identify strategies for its prevention and treatment.

100 Deals associated with Neublastin

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15438

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Intervertebral Disc Disease	Phase 2	United States	Biogen, Inc.	01 Jun 2013
Lumbar Radiculopathy	Phase 2	United States	Biogen, Inc.	01 Jun 2013
Sciatica	Phase 2	United States	Biogen, Inc.	01 Jun 2013
Sciatica	Phase 2	United States	Biogen, Inc.	01 Jun 2013
Neuralgia	Phase 2	Denmark	NsGene A/S	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EASL2021	Not Applicable	Hepatocellular Carcinoma serum ARTN concentration	56	artemin (High ARTN)	(mcpucwcicx) = zdghztctre xfqrafyibp (rnyjdjzjwm )	Negative	23 Jun 2021
				artemin (Low ARTN)	(mcpucwcicx) = vtwyenrzdc xfqrafyibp (rnyjdjzjwm )
NCT01873404 (SPRINT, Pubmed \| Pain Physician) Manual	Phase 2	Lumbosacral Radiculopathy	176	Neublastin	(jfikykstvi): difference = -0.75 (95% CI, -1.59 to 0.08) View more	Positive	01 Sep 2017
				Placebo
NCT01405833 (Pubmed \| Br J Clin Pharmacol) Manual	Phase 1	Sciatica	28	BG00010 (In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ))	(xiaxeyhjpf) = Most AEs were mild tptpihdhsi (imygploqhe ) View more	Positive	01 Jul 2016
				BG00010 (in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ).)
NCT00961766 (Pubmed \| J Biol Chem \| PLoS One) Manual	Phase 1	Sciatica	48	BG00010	(gvvirgnedd) = the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache wmyijotuvj (aypwtrdyup )	Positive	11 May 2015
				Placebo

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

login

or

view full example data

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

Understand key drug designations in just a few clicks with Synapse.

login

or

view full example data

Understand key drug designations in just a few clicks with Synapse.

Neublastin

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation