Author: Wittich, Christoph ; Lang, Alexander ; Padrini, Giacomo ; Floss, Doreen M ; Ettich, Julia ; Moll, Jens M ; Cruz, Patricia Rodrigues ; Köhrer, Karl ; Petzsch, Patrick ; Seibel, Christiane ; Scheller, Jürgen ; Rafii, Puyan

Ciliary neurotrophic factor (CNTF) activates cells via the non-signaling α-receptor CNTF receptor (CNTFR) and the two signaling β-receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). The CNTF derivate, Axokine, was protective against obesity and insulin resistance, but clinical development was halted by the emergence of CNTF antibodies. The chimeric cytokine IC7 used the framework of interleukin (IL-)6 with the LIFR-binding site from CNTF to activate cells via IL-6R:gp130:LIFR complexes. Similar to CNTF/Axokine, IC7 protected mice from obesity and insulin resistance. Here, we developed CNTF-independent chimeras that specifically target the IL-6R:gp130:LIFR complex. In GIL-6 and GIO-6, we transferred the LIFR binding site from LIF or OSM to IL-6, respectively. While GIO-6 signals via gp130:IL-6R:LIFR and gp130:IL-6R:OSMR complexes, GIL-6 selectively activates the IL-6R:gp130:LIFR receptor complex. By re-evaluation of IC7 and CNTF, we discovered the Oncostatin M receptor (OSMR) as an alternative non-canonical high-affinity receptor leading to IL-6R:OSMR:gp130 and CNTFR:OSMR:gp130 receptor complexes, respectively. The discovery of OSMR as an alternative high-affinity receptor for IC7 and CNTF designates GIL-6 as the first truly selective IL-6R:gp130:LIFR cytokine, whereas GIO-6 is a CNTF-free alternative for IC7.

02 Jan 2024·Regenerative Biomaterials

Injectable drug-loaded thermosensitive hydrogel delivery system for protecting retina ganglion cells in traumatic optic neuropathy

Article

Author: Wang, Lei ; Deng, Yudan ; Chen, Hao ; Jiang, Yan ; Ding, Jiangtao ; Li, Lingli ; Wang, Wenwen ; Nan, Kaihui ; Yao, Yili ; Liu, Zhiqiang

AbstractCurrently, generalized therapy for traumatic optic neuropathy (TON) is lacking. Various strategies have been developed to protect and regenerate retinal ganglion cells (RGCs) after TON. Intravitreal injection of supplements has been approved as a promising approach, although serious concerns, such as low delivery efficacy and pain due to frequent injections, remain. In this study, we tested an injectable thermosensitive hydrogel drug delivery system engineered to deliver ciliary neurotrophic factor (CNTF) and triamcinolone acetonide (TA). The results of rheological studies showed that the prepared drug-loaded hydrogel possessed a suitable mechanical modulus of ∼300 Pa, consistent with that of vitreum. The hydrogel exhibited thermosensitive with sustained drug release performance. In vitro co-culture of the CNTF-loaded hydrogel system with primary RGCs also induced significant axon regeneration, with 38.5% increase in neurite length, indicating the regenerative response of the thermosensitive hydrogel drug delivery system. A Sprague-Dawley rat optic nerve crush model was constructed and applied to determine the neuroprotective and regenerative capacities of the system. The results demonstrated that a single intravitreal injection of the drug-loaded hydrogel (PLGA-PEG-PLGA + TA or PLGA-PEG-PLGA + CNTF) significantly increased RGC survival at both 14 and 28 days. The RGC survival rate was 31.05 ± 1.41% for the drug-loaded hydrogel system (the control group was 16.79 ± 1.50%) at Day 28. These findings suggest that the injectable drug-loaded thermosensitive hydrogel delivery system is a promising therapeutic tool for treating optic nerve degeneration.

01 Jan 2023·Poultry Science

Dietary supplementation with astaxanthin alleviates ovarian aging in aged laying hens by enhancing antioxidant capacity and increasing reproductive hormones

Article

Author: Zhao, Qingyu ; He, Weizhao ; Wang, Hao ; Zhang, Junmin ; Tang, Chaohua

We investigated the effects of astaxanthin supplementation on the egg quality, antioxidant capacity, and ovarian aging of aged laying hens. Six groups of 68-wk-old Hy-line brown laying hens with six replications each, fifteen chickens in each replicate were fed for 12 wk. The control group was fed a basal diet, the positive control group was fed the basal diet supplemented with 100 mg/kg vitamin E, and the experimental groups were fed the basal diet supplemented with 15 mg/kg, 30 mg/kg, 45 mg/kg, or 60 mg/kg astaxanthin (Ax15, Ax30, Ax45, and Ax60, respectively). The results showed that astaxanthin accumulated in the egg yolks and improved egg yolk color (P < 0.01) and Haugh unit (P < 0.05). Compared with the control group, the experimental groups a higher number of follicles in the ovary and a lower rate of atresia (P < 0.01). Astaxanthin increased the expression of nuclear factor e2-related factor 2 (NRF2) in the ovary (P < 0.05), enhanced the antioxidant capacity of aged laying hens (P < 0.05), and reduced cellular apoptosis (P < 0.05). In addition, astaxanthin improved serum reproductive hormone levels (follicle-stimulating hormone, luteinizing hormone, and progesterone) (P < 0.05) with a maximum value observed in Ax60. However, astaxanthin had no effects on estrogen level (P > 0.05). The expression of FSHR and CYP11A1 increased in the follicular granulosa cells (P < 0.05). Therefore, astaxanthin prevented ovarian aging by improving the antioxidant capacity of laying hens and promoting the production of reproductive hormones. The declining reproductive performance of laying hens in the late laying period may be improved with astaxanthin supplementation.

News (Medical) associated with Dapiclermin

08 Nov 2024

·www.businesswire.com

Neurotech Provides Update on BLA for NT-501 as a Treatment for Macular Telangiectasia Type 2 (MacTel)

CUMBERLAND, R.I.--( BUSINESS WIRE )--Neurotech Pharmaceuticals, Inc., an innovator in sustained drug delivery for chronic retinal diseases, today announced that the U.S. Food and Drug Administration (FDA), has extended the Prescription Drug User Fee Act (PDUFA) goal date by three months to allow time required for the FDA to review additional data provided by the Company in response to recent requests from the FDA. The new PDUFA goal date for the biologics license application (BLA) of NT-501 (revakinagene taroretcel) as a treatment for Macular telangiectasia type 2 (MacTel) is March 18, 2025. “We are committed to providing the Agency any information needed to complete the review of the NT-501 BLA,” said Richard Small, Chief Executive Officer. “Neurotech will continue in our effort to bring this important therapy to MacTel patients.” About Macular Telangiectasia (MacTel) Macular Telangiectasia Type 2 (MacTel), or idiopathic juxtafoveal macular telangiectasia type 2, is a rare neurodegenerative disease with characteristic localized retinal degeneration and secondary alterations of the retinal vasculature. 1 MacTel typically affects both eyes and causes a gradual deterioration in central vision. About Encapsulated Cell Therapy (ECT) The ECT platform is a cell-based delivery system designed to provide long-term, sustained delivery of therapeutic proteins for the treatment of chronic retinal diseases. This versatile platform consists of a small, semi-permeable capsule containing proprietary allogeneic retinal pigment epithelium (RPE) cells genetically engineered to produce specific therapeutic proteins for targeted disease treatment. The capsule is surgically inserted into the patient’s vitreous and sutured to the sclera during an outpatient procedure. Once in place, the capsule's semi-permeable membrane allows essential nutrients to enter, while also permitting the therapeutic proteins to exit into the vitreous, providing targeted and continuous treatment. Simultaneously, the membrane protects the encapsulated RPE cells from the host's immune system, ensuring their long-term survival and functionality. About NT-501 Implant NT-501 leverages our ECT platform to deliver CNTF for the treatment of chronic retinal diseases, such as MacTel. CNTF is a potent neuroprotective protein that promotes the survival and maintenance of photoreceptors. This targeted therapy provides sustained delivery of CNTF, aiming to slow retinal degeneration and potentially improve long-term visual outcomes for patients. About Neurotech Pharmaceuticals, Inc. Neurotech Pharmaceuticals, Inc. is a private, clinical stage biotechnology company and an innovator in sustained drug delivery for chronic retinal diseases. The core platform technology, ECT, enables continuous production of therapeutic proteins to the back of the eye. For more information about us, please visit https://www.neurotechpharmaceuticals.com . 1. Charbel Issa P, Gillies MC, Chew EY, Heeren TFC, Bird AC, Peto T, Holz FG, Scholl HPN (2013) Macular Telangiectasia Type 2.

Cell Therapy

20 Jun 2024

·www.biospace.com

Neurotech Pharmaceuticals, Inc. Receives Priority Review of Biologics License Application (BLA) for NT-501 (revakinagene taroretcel) as a Treatment for Macular Telangiectasia Type 2 (MacTel)

- Priority review granted with a PDUFA goal date set for December 17, 2024. CUMBERLAND, R.I.--(BUSINESS WIRE)-- Neurotech Pharmaceuticals, Inc., an innovator in sustained drug delivery for chronic retinal diseases, announces that the U.S. Food and Drug Administration (FDA), has determined that the Biologic License Application (BLA) for NT-501, an investigational encapsulated cell therapy for the treatment of MacTel, is sufficiently complete to permit a substantive review. The application has a prescription drug user fee act (PDUFA) goal date of December 17, 2024. MacTel is a progressive, neurodegenerative disease of the retina that results in the deterioration of central vision, significantly impacting patients' quality of life. NT-501 is an ocular implant designed to deliver sustained therapeutic doses of ciliary neurotrophic factor (CNTF) directly to the retina to slow the progression of the disease. “This is a significant achievement for Neurotech,” said Richard Small, Chief Executive Officer. “I would like to express my gratitude to our employees for reaching this important milestone.” About Macular Telangiectasia (MacTel) MacTel, or idiopathic juxtafoveal macular telangiectasia, is a rare neurodegenerative disease with characteristic localized retinal degeneration with secondary alterations of the retinal vasculature.1 MacTel typically affects both eyes and causes deterioration in central vision impacting patients’ quality of life. About Encapsulated Cell Therapy (ECT) The ECT platform is a cell-based delivery system that was designed to provide long-term, sustained delivery of therapeutic proteins for the treatment of chronic retinal diseases. This versatile platform consists of a small, semi-permeable capsule containing proprietary allogeneic RPE cells genetically engineered to produce specific therapeutic proteins for targeted disease treatment. The capsule is surgically inserted into the patient’s vitreous and sutured to the sclera during an outpatient procedure. Once in place, the capsule's semi-permeable membrane allows essential nutrients to enter, while also permitting the therapeutic proteins to exit into the vitreous, providing targeted and continuous treatment. Simultaneously, the membrane protects the encapsulated RPE cells from the host's immune system, ensuring their long-term survival and functionality. About NT-501 Implant NT-501 leverages our ECT platform to deliver CNTF for the treatment of chronic retinal diseases, such as MacTel. CNTF is a potent neuroprotective protein that promotes the survival and maintenance of photoreceptors. This targeted therapy provides sustained delivery of CNTF, aiming to slow retinal degeneration and potentially improve long-term visual outcomes for patients. About Neurotech Pharmaceuticals, Inc. Neurotech Pharmaceuticals, Inc. is a private, clinical stage biotechnology company and an innovator in sustained drug delivery for chronic retinal diseases. The core platform technology, ECT, enables continuous production of therapeutic proteins to the back of the eye. For more information about us, please visit . 1. Charbel Issa P, Gillies MC, Chew EY, Heeren TFC, Bird AC, Peto T, Holz FG, Scholl HPN (2013) Macular Telangiectasia Type 2.

Cell TherapyPriority Review

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KEGG	Wiki	ATC	Drug Bank
D03647	-	-	DB05344

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 3	-	Regeneron Pharmaceuticals, Inc.	-
Huntington Disease	Phase 3	United States	Regeneron Pharmaceuticals, Inc.	-
Obesity	Phase 3	-	Regeneron Pharmaceuticals, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2007	Not Applicable	-	-	CNTF	gwddyxyqmt(talbhtvmcc) = sflcfwtkfo jtzgjkomct (debfwhinta ) View more	-	01 May 2007
				CNTF+cAMP	gwddyxyqmt(talbhtvmcc) = cgvkcywcpd jtzgjkomct (debfwhinta ) View more
ARVO2005	Not Applicable	-	-	Vehicle	(jyccrzrvcb) = ejqtaqxrej clpzqisahi (bcxrqyoebl )	-	01 May 2005
				BDNF	(jyccrzrvcb) = nfqjzslwfb clpzqisahi (bcxrqyoebl )
ARVO2002	Not Applicable	-	-	Ciliary Neurotrophic Factor (PGK-CNTF)	jnksbcipef(zskjyiespf) = ntllnquwwf luhxqoyume (dyecahsoma ) View more	-	01 Dec 2002
ASGCT2002	Not Applicable	Glaucoma	-	Ciliary Neurotrophic Factor (PGK-CNTF)	agokfafjvh(kayawuaqae) = fshebhnrqx wiymdwbsfv (pnyrghupaa )	-	01 May 2002
				Ciliary Neurotrophic Factor (PGK-lacZ)	agokfafjvh(kayawuaqae) = rfmticiiun wiymdwbsfv (pnyrghupaa )

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