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Biologics Offer New Hope for Complex Diseases

The article discusses how biologics, complex therapeutic agents derived from living organisms such as monoclonal IgG antibodies, offer promising new treatment options for multifactorial chronic diseases like Alzheimer’s, which are difficult to treat with traditional small molecule drugs due to their complex causative factors.

Complex chronic diseases like diabetes, sickle cell anemia, and Alzheimer’s disease are multifactorial conditions, meaning they’re influenced by many factors, such as infectious causes, genetic predispositions, and environmental conditions. This makes them uniquely difficult to treat. For example, Alzheimer’s disease neurodegeneration is thought to be influenced by four intertwined factors: A-beta plaques, tau tangles, small vessel leaks, and TDP-43 hardening. Developing therapeutics to treat conditions like Alzheimer’s, which have complex causative factors, is incredibly challenging.

Biologics for Complex Disease

Complex diseases have been challenging to address with chemically synthesized small molecule drugs. Biologics offer new hope. Biologics are large, complex treatment entities derived from living organisms, such as bacteria, yeast, or mammalian cells. They target specific cells in the body to stimulate or suppress the immune system and are typically administered through injection or infusion. While biologics can be more expensive than traditional drugs due to the complexity of their production processes, they can also offer significant benefits to patients with complex medical conditions. Examples of biologics include cytokines, growth factors, certain vaccines, cell therapies, gene therapies, RNAi, and monoclonal antibodies, which are the focus here.

Example: IgG Antibodies

There are five main classes of antibodies (immunoglobulins, Ig), with IgG being the most prevalent. Although the smallest in size, IgG antibodies account for 80% of total antibodies in serum. They are the main antibody associated with secondary responses that neutralize toxins. IgG antibodies are made of symmetrical heavy and light protein chains shaped like the letter Y, where the base (constant Fc region) interacts with immune-system components and the two arms (variable Fab region) recognize and interact with an antigen.

Distinct regions of specific chromosomes control the creation of proteins that comprise an antibody. In humans, chromosomes 2, 22, and 14 all contribute to the creation of IgG antibodies. The antibody assembly process is incredibly complex, with different building blocks, originating from different gene fragments, coming together in a combinatorial fashion. These different assembly combinations may also have junctional and somatic differences, resulting in a tremendous amount of antibody diversity.

Antibody Analysis

Analyzing the impact of therapeutic antibody candidates’ diversity is an essential part of antibody discovery efforts and, for many teams, a key challenge as well.

For example, B-cell antibody repertoire analysis involves B-cells, which are white blood cells produced in the bone marrow that play a key role in the body’s immune response to infection. They produce antibodies to help attack foreign invaders by binding to and neutralizing harmful proteins (antigens), preventing antigens from entering cells, or marking antigens for destruction by other immune cells. To study B-cell antibodies, researchers must unite, analyze, and re-analyze data from both mass-spectrometry protein analysis (Ig-Seq) and sequence analysis (BCR-Seq) to attain a more complete picture, make the best possible research decisions, and uncover new insights.

While combining and recombining different types of research data and analyses is imperative, it’s also incredibly challenging without a flexible end-to-end R&D platform that helps discovery teams optimize both dataflows and workflows.

Next Steps

Read more about the ways Dotmatics is supporting research composability and multi-dimensional discovery with a comprehensive and advanced biologics R&D solution.