Ciliary neurotrophic factor encodes Human CNTF gene and is a polypeptide hormone and neurotrophic factor whose actions have mainly been studied in the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neural populations including astrocytes. It is a hypothalamic neuropeptide that is a potent survival factor for neurons and oligodendrocytes.
>99% by SDS-Page and HPLC analysis
<0.001 EU per 1 μg of the peptide by the LAL method
Ciliary neurotrophic factor
Investigated for use/treatment in eye disorders/infections, macular degeneration, and retinal disorders (unspecified).
Examples of Clinical Use:
NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, The product directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT).
Mechanism of action:
NT-501 is an intraocular, cell containing polymer implant designed to provide the continuous, long-term release of the therapeutic protein, Ciliary Neurotrophic Factor (CNTF), directly into the back of the eye by means of the Company's proprietary Encapsulated Cell Technology (ECT).
1. Introduction to Ciliary neurotrophic factor (CNTF)
Ciliary neurotrophic factor (CNTF) is a protein that belongs to the neurotrophic factor family. It plays a crucial role in the development, function, and protection of various types of nerve cells in the body. CNTF was initially discovered for its ability to promote the survival of ciliary ganglion neurons, hence its name.
Human CNTF is produced by a variety of cell types including glial cells, astrocytes, and certain immune cells. It exerts its biological effects by binding to the CNTF receptor complex, which consists of the CNTF receptor alpha (CNTFRα) and the leukemia inhibitory factor receptor beta (LIFRβ). The binding of CNTF to this receptor complex triggers a signaling cascade that leads to the activation of various intracellular pathways promoting cell survival, differentiation, and maintenance.
CNTF is known to have broad effects on the nervous system. It has been shown to promote the survival and differentiation of motor neurons, which are responsible for controlling muscle movement. This has led to investigations into the potential therapeutic use of CNTF in treating motor neuron disorders such as amyotrophic lateral sclerosis (ALS).
In addition to motor neurons, CNTF also affects other types of neurons including sensory neurons, sympathetic neurons, and interneurons. It plays a role in the development and maintenance of these neurons and has been shown to have therapeutic potential in neurodegenerative conditions and nerve injuries.
Furthermore, CNTF has been studied for its potential role in weight regulation and metabolism. Studies have shown that it can increase energy expenditure and decrease appetite, making it a potential target for combating obesity.
Despite its therapeutic potential, the clinical application of CNTF has faced challenges, including difficulties in delivering the protein to the desired sites in the body and limited understanding of its complex mechanisms of action. Nevertheless, researchers continue to explore the possibilities of CNTF for the treatment of various neurological disorders and metabolic diseases.
2. Composition and structure of Ciliary neurotrophic factor
The human CNTF protein is composed of 200 amino acids and has a molecular weight of approximately 22 kDa. It is a glycosylated protein, meaning it contains carbohydrate side chains that are attached to specific amino acid residues.
The structure of human CNTF consists of four alpha helices arranged in a bundle configuration. These helices are connected by loops and turns, creating a compact globular structure. The tertiary structure of CNTF is stabilized by disulfide bonds between specific cysteine residues.
Human CNTF is secreted as a soluble protein and can be found in various tissues and bodily fluids. It can bind to its receptor complex, which consists of CNTFRα and LIFRβ, leading to the activation of downstream signaling pathways.
The glycosylation of CNTF is essential for its stability, solubility, and biological activity. It has been shown that the removal of the carbohydrate side chains can impair the ability of CNTF to bind to its receptors and induce signaling.
3. Clinical application of Ciliary neurotrophic factor
Ciliary neurotrophic factor (CNTF) has shown promising potential in various clinical applications. Here are some examples:
Neurodegenerative diseases: CNTF has been studied for its neuroprotective and neuroregenerative properties, making it a potential therapeutic tool for neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease. In animal models, CNTF administration has demonstrated the ability to preserve and regenerate neurons, promote neurite outgrowth, and improve motor function. Clinical trials investigating the use of CNTF in ALS have shown mixed results, but research in this area continues.
Retinal diseases: CNTF has shown promise as a therapeutic agent for retinal disorders, including retinitis pigmentosa and macular degeneration. It has the ability to rescue photoreceptor cells from degeneration, improve retinal function, and enhance visual acuity. Clinical trials exploring the use of CNTF implants, delivered directly to the eye, have shown encouraging results with improvements in visual function observed in some patients.
Obesity and metabolic disorders: CNTF has been investigated as a potential treatment option for obesity and metabolic disorders due to its ability to regulate energy balance and promote weight loss. Clinical trials testing CNTF as a subcutaneous injection or an intranasal spray have shown reduced body weight and improved insulin sensitivity. Further studies are needed to determine the long-term effectiveness and safety of CNTF in this context.
Nerve injury and repair: CNTF has been studied for its potential in nerve injury and repair. It has been shown to promote the survival and regeneration of damaged nerves, improve motor function, and reduce pain in animal models. Clinical trials exploring the use of CNTF in peripheral nerve injury and spinal cord injury are ongoing, with promising preliminary results.
While CNTF holds promise for various clinical applications, more research is needed to better understand its mechanisms of action, optimal dosages, and potential side effects. Further clinical trials are necessary to determine its safety and efficacy in humans.
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