Protein-depends Neurological Disease Solutions

Protein-based therapies have been so successful in the clinic that their potential is now recognized as never before. Creative Biolabs is an independent contract services organization focused on neuroscience. Since its inception, it has provided a full range of in vitro and in vivo services to pharmaceutical, biotechnology, and research institutions.

Overview of Protein Therapy

Therapeutic proteins, such as antibodies, constitute the fastest-growing category of drugs used in diverse clinical settings. Among the wide range of biologicals (i.e., protein therapeutic candidates) for the treatment of CNS diseases, neurotrophic factors and recombinant antibodies hold, as protein classes, the greatest promises. Antibody-based therapies have proven efficacious in a variety of diseases. It is established that proteins fundamentally contribute to the maintenance of cellular function and that protein stability is a major mechanism underlying human diseases, such as cancer and neurological diseases. The direct route from the nose to the brain is proving to be a universal strategy for non-invasively delivering many candidates therapeutic proteins to the central nervous system in animal models and provides an exciting opportunity for delivering biological agents to the human brain for the treatment of nervous system and neurodegenerative diseases.

Fig.1 Protein therapy. (Morren, 2021)

Functions of Therapeutic Proteins

• Replacing damaged proteins
• Increasing the efficiency of an existing pathway
• Providing a unique function
• Interfering with an organism or molecule
• Delivering different proteins or compounds

Different Classes of Intranasally Delivered Therapeutic Proteins

The proteins are under investigation for a therapeutic application in CNS diseases, through the intranasal pathway, focusing on neurotrophic factors, neuropeptides, and antibody domains.

• Neurotrophic Factors

Neurotrophic factors have great potential as protein therapies in the central nervous system. In the CNS, mature basal forebrain cholinergic neurons (BFCNs) are dependent on the availability of NGF for their phenotypic maintenance and survival after lesions or CNS insults. Beyond its neurotrophic actions on BFCNs, NGF displays a direct anti-amyloidogenic and anti-neurodegenerative property. For an NGF-based treatment, the goal is to develop a non-invasive delivery system capable of targeting NGF to the target brain region, limiting systemic leakage and access to peripheral sensory nerve endings.

• Other Protein Therapeutics: Insulin, Cytokines, Neuropeptides

Insulin is a protein hormone involved in muscle glucose metabolism, which affects many aspects of neuronal physiology. Peptide activity scanning identified NAP, an active fragment of ADNP, endowed with the same neuroprotective properties as the entire protein. The NAP showed neuroprotective effects against Ab peptide toxicity in both cell culture and neurodegenerative animal models.

• Recombinant Antibodies

Antibody-based therapies have shown high efficacy in a variety of diseases and are considered safer than small chemical molecules because of their high target specificity. Intranasal injection of antibodies or antibody fragments may be an alternative approach to immunotherapy, opening the field of central nervous system therapy to large-scale recombinant antibody biologics.

Fig.2 Schematic view of the different fate and pathways for protein/drug absorption and transport from the nasal cavity to the CNS. (Malerba, 2011)

Creative Biolabs offers well-established and innovative One-Stop-Shop solutions. You can count on our skilled and passionate workforce to find the most suitable path. We can make your protein therapy research project easier. Please feel free to contact us to discuss your need.

References

1. Morren, M.A.; et al. Challenges in Treating Genodermatoses: New Therapies at the Horizon. Frontiers in Pharmacology. 2021, 12.
2. Malerba, F.; et al. Intranasal delivery of therapeutic proteins for neurological diseases. Expert opinion on drug delivery. 2011, 8(10): 1277-1296.