The Use of Antibody Therapy in Rare Disease Research

In this article, we continue our look into rare disease research. Earlier, we began our examination of the subject (read the article here). In that article, we looked at rare disease in detail and explained how common rare diseases actually are with over 7,000 known diseases. We also explored some of the common origins for known rare diseases and explained how this knowledge helps researchers develop treatments for those conditions using small molecules (click here). We looked at the small molecule platform and its opportunities in the fight against rare disease. Here, we will look at the use of antibody therapy in rare disease research.

What is Antibody Therapy?

Antibody therapy is still a relatively new research technology. This class of research originated in 1986 when the first monoclonal antibody (mAb) received approval for therapeutic treatment of organ allograft rejection and has grown from there. Today, it is the dominant treatment for many conditions, including immune disorders and cancers.

In essence, antibodies impact signal pathways and recruit elements in the body to complete certain tasks, such as delivering a cytotoxin or neutralizing a circulating factor. B lymphocytes make monoclonal antibodies (mAb). These mAb recognize and target specific antigens. Antibodies in modern research can be full-length or focus on engineering antigen-binding fragments called Fab. The latter allows researchers to target particular applications such as the back of the eye and they carry the benefit of faster clearance. The reduction in systemic bioavailability thusly reduces the potential for toxicity. There are also bispecific antibodies (BsAbs). They allow the immune system to have two targets at once. Antibody therapy includes antibody constant regions or Fcs as well. These are fused to a non-antibody protein to create a standalone treatment (Fc-fusion protein) or fused to small molecules to create ADCs.

Clinical Success in Antibody Research

Most of the therapies based on mAB that have approval center on rare diseases within oncology, but there is a potential for this drug development platform to be crucial in targeting disease-linked proteins. For example, there is a mAB called Eculizumab that targets the C5 protein. It was originally used as a treatment for the blood disease Paroxysmal Nocturnal Hemoglobinuria (PNH). However, it also has applications in the kidney condition Atypical Hemolytic-Uremic Syndrome (AHUS) and the neuromuscular disease Myasthenia Gravis (MG). Targeting the C5 protein helps people with each of those conditions. For this reason, it is not unusual to see mAB in umbrella trials.

Strengths and Limitations of the Platform

The major strength of antibody therapy is that it is highly specific. Think of it as the pharmaceutical version of the adage “Aim small, miss small.” Because antibody therapy is so targeted, it reduces the risk of toxicity. This is particularly important in rare disease research and the treatment of those conditions because long-term treatment is frequently required. After all, most rare diseases have no cure per se. Symptom management is the best possible outcome, and that means taking a drug or treatment for a very long time.

That said, there are important limitations to antibody therapy. The relative size of mAbs is quite large and that limits how well the derived therapies can penetrate cells or tissues. As a result, desirable targets like intracellular proteins are virtually off the table. Nanobodies may provide a possibility, but not in all cases. Further, the costs of manufacturing mAb-based treatments can be prohibitive. This drug platform leverages cultures of mammalian cells and they must be purified. Finally, there is the issue of injection. Many mAb treatments are injected and this may result in injection-site issues over time.

Answering the Challenge of Rare Disease Research

Antibody research in rare disease is relatively uncommon but that may change going forward. The ability to identify mAbs is improving all the time. This helps reduce the manufacturing costs associated with antibody-based treatments and makes the process easier overall. In addition, the ability of artificial intelligence to match specific mechanisms using pathway information from large-scale gene sequencing projects may also be beneficial.

Please note, this post is the third in a series of eight articles centered on trends in rare disease research:

  1. Rare Disease Research
  2. Small Molecules
  3. Antibodies
  4. Protein Replacements
  5. Oligonucleotides
  6. Gene Therapy
  7. Drug Repurposing
  8. The Future of Rare Disease Research

For more information on Allucent’s rare disease experience, visit our website.


  • Tambuyzer, E., Vandendriessche, B., Austin, C.P. et al. Publisher Correction: Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov (2020).
  • Institute of Medicine (US) Committee on Accelerating Rare Diseases Research and Orphan Product Development; Field MJ, Boat TF, editors. Rare Diseases and Orphan Products: Accelerating Research and Development. Washington (DC): National Academies Press (US); 2010. 2, Profile of Rare Diseases. Available from:
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