A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Using a Bayesian Adaptive Design to Assess the Efficacy, Safety, Tolerability, and Serum Exposure of Multiple Doses of BG00010 (Neublastin) in Subjects With Painful Lumbar Radiculopathy

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

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

100 Translational Medicine associated with Neublastin

100 Patents (Medical) associated with Neublastin

172

Literatures (Medical) associated with Neublastin

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 ; Shahbaz, Shima ; Sligl, Wendy ; 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.

20 Mar 2024·Zhonghua shao shang yu chuang mian xiu fu za zhi

[Effect and mechanism of human adipose-derived stem cell exosomes on diabetic peripheral neuropathy].

Article

Author: Guan, H ; Xiao, D ; Wang, X J ; Hao, T ; Ji, P ; Jia, Y H ; Zhang, W F ; Tao, K ; Cao, T ; Wang, J

Objective: To investigate the changes of artemin protein expression in diabetic peripheral neuropathy (DPN) and to explore the regulatory effect of human adipose-derived stem cell (ADSC) exosomes on the change of artemin protein expression. Methods: This research was a prospective observational clinical research combined with experimental research. Thirteen DPN patients (9 males and 4 females, aged 32 to 68 years) who were admitted to the First Affiliated Hospital of Air Force Medical University (hereinafter referred to as our hospital) from May 2022 to October 2023 and met the inclusion criteria were selected as DPN group, and 5 non-diabetes patients (4 males and 1 female, aged 29 to 61 years) who were admitted to our hospital in the same period of time and met the inclusion criteria were selected as control group. The toe nerve or sural nerve tissue in the abandoned tissue after debridement or amputation of patients in the two groups was collected. The pathological changes of nerve tissue were observed after hematoxylin-eosin staining; the protein expressions of S100β and artemin in nerve tissue were observed after immunofluorescence staining, and the artemin protein expression was quantified; the protein and mRNA expressions of artemin were detected by Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction, respectively (the sample number in DPN group and control group was 13 and 5, respectively). Twelve male C57BL/6 mice aged 3 to 5 days were collected to isolate Schwann cells, and the cells were divided into conventional culture group cultured routinely, high glucose alone group (cultured with high concentration of glucose solution only), and high glucose+exosome group (cultured with high concentration of glucose solution and extracted human ADSC exosomes). After 24 hours of culture, the cell proliferation activity was detected by cell counting kit 8 (n=6). After 48 hours of culture, the protein expression of artemin was detected by Western blotting (n=3). Results: Compared with those in control group, the neural supporting cells decreased and the inflammatory cells increased in the nerve tissue of patients in DPN group, showing typical manifestations of nerve injury. Immunofluorescence staining showed that compared with those in control group, the nuclei was more, and the protein expression of S100β was lower in nerve tissue of patients in DPN group. The protein expression of artemin in nerve tissue of patients in DPN group was 71±31, which was significantly lower than 1 729±62 in control group (t=76.92, P<0.05). Western blotting detection showed that the protein expression of artemin in nerve tissue of patients in DPN group was 0.74±0.08, which was significantly lower than 0.97±0.06 in control group (t=5.49, P<0.05). The artemin mRNA expression in nerve tissue of patients in DPN group was significantly lower than that in control group (t=7.65, P<0.05). After 24 hours of culture, compared with that in conventional culture group, the proliferation activities of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the proliferation activity of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). After 48 hours of culture, compared with those in conventional culture group, the protein expressions of artemin of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased (P<0.05); compared with that in high glucose alone group, the protein expression of artemin of Schwann cells in high glucose+exosome group was significantly increased (P<0.05). Conclusions: The protein expression of artemin in nerve tissue of DPN patients is lower than that in normal nerve tissue, which may be related to the reduction of proliferation activity of Schwann cells by high glucose. Human ADSC exosomes may improve the proliferation activity of Schwann cells by increasing artemin protein expression, thereby delaying the progression of DPN.

100 Deals associated with Neublastin

External Link

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R&D Status

10 top R&D records.

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

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EASL2021	Not Applicable	Hepatocellular Carcinoma serum ARTN concentration	56	artemin	jssihyuumh(vhgfrzcocu) = idfumhipzx ikxlaljxtg (rzprzydpki )	Negative	23 Jun 2021
				artemin	jssihyuumh(vhgfrzcocu) = uhvefvrrrk ikxlaljxtg (rzprzydpki )
NCT01873404 (SPRINT, Pubmed \| Pain) Manual	Phase 2	Lumbosacral Radiculopathy	176	Neublastin	(hercygnsie): 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) ))	(sxbwddpoey) = Most AEs were mild lkmlmvlheo (xjsszxsfyt ) 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 \| PLoS One) Manual	Phase 1	Sciatica	48	BG00010	(hzylfykdzh) = the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache nmtqpvtijc (pjdzakfzmc )	Positive	11 May 2015
				Placebo

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