Indication

Complement-Related Diseases

The complement system historically has been recognized as a component of immune defense against foreign invaders (e.g. bacteria, viruses, and fungi) by opsonization and cytolysis. Recent studies showed that its versatile functions extend far beyond the elimination of microbes. The complement has verified as a surveillance system to discriminate healthy and altered host cells (e.g. apoptotic and necrotic cells and their fragments), because of the capacity to recognize and dispel the damaged "self" components.

By sending "danger" signals and orchestrating immune responses, complement system contributes substantially to homeostasis, but it may damage healthy host cells and tissues if not properly controlled. With a major functional linkage with other systems, including coagulation, adaptive immunity, Fc receptors, TLRs, and noninflammatory disposal mechanisms, the intricate complement network requires rigorous regulation to maintain appropriate homeostasis. Excessive or insufficient activation will break the delicate balance between complement activation and regulation, leading a variety of disease, including:

Classification of Complement Deficiencies

The complement system consists of more than 30 proteins and regulators that play a key role in innate immunity by mediating processes such as conditioning, pathogen lysis, and inflammation. Nearly 50% of all complement proteins serve as regulators or inhibitors in the amplification cascade, so any absence or suboptimal function of the proteins gives rise to severe clinical disease.

Based on the pathway of complement activation, complement deficiencies can broadly be categorized into the following three groups.

Complement deficiencies can broadly be broadly categorized as primary or secondary based on their origin and underlying mechanisms.

• Primary complement deficiencies arise from genetic mutations that disrupt the synthesis, structure, or function of complement components or regulatory proteins. These deficiencies are often hereditary and can lead to recurrent infections, immune complex diseases, or autoimmune conditions.
• Secondary complement deficiencies occur as a result of acquired conditions or diseases that lead to the depletion, consumption, or functional inhibition of complement components. These deficiencies are not caused by genetic mutations but by pathological processes that impact complement system functionality.

Clinical studies reveal that excessive activation of complement system causes massive accumulation of complement components in the serum of rheumatoid arthritis (RA). In addition, age-related macular degeneration (AMD) and coagulation disorders are related to the excessive accumulation of complement.

Fig. 1 Illustration of complement system related CNS diseases.^{1, 2}

Targeting Complement Pathways for Drug Discovery

By targeting complement pathways, developing biologics to modulate complement activity, and harnessing the power of gene therapy, researchers and biopharmaceutical companies are opening new avenues for treating these complex diseases. At Creative Biolabs, we are dedicated to complement systems research, providing cutting-edge solutions to advance complement therapies.

Based on our experienced team of experts and well-established complement platform, Creative Biolabs provides a great variety of therapeutic antibodies, inhibitors, soluble complement regulators, as well as customized services to help our customers develop novel drugs for complement-related diseases.

• Alternative therapies - This therapy involves the use of purified or recombinant complement proteins to restore function, such as C1-INH concentrates, plasma-derived C3 or C5 proteins.
• Complement inhibitors - Targeted inhibitors are effective in cases of complement overactivation or dysregulation. The future of complement component inhibitor development promises to provide more targeted and effective treatments for a wide range of diseases.
• Small molecule modulators - Small molecules targeting complement activation pathways are being developed to modulate complement activity in a tissue-specific or pathway-selective manner. These approaches are particularly useful for chronic diseases associated with complement, such as AMD and Alzheimer's disease.
• Gene therapy - Gene therapy holds the promise of addressing genetic defects in complement components.

Related Products

Our comprehensive complement platform offers a great number of complement-related products in a rapid and cost-effective manner. If you are interested, please feel free to contact us for more details.

Resources

Complement Testing Services

Complement Therapeutics Services Brochure

Podcast

References

1. Shinjyo, Noriko, Wataru Kagaya, and Marcela Pekna. "Interaction between the complement system and infectious agents–a potential mechanistic link to neurodegeneration and dementia." Frontiers in Cellular Neuroscience 15 (2021): 710390.
2. under Open Access license CC BY 4.0, without modification.

• Autoimmune Disease
• Nephropathy
• Osteology
• Genetic Disease
• Infection
• Neurology
• Inflammatory Disease
• Ophthalmology
• Cardiovascular Disease