Science Pool

Gene Therapy: The Future of Medicine

Curing paraplegia

In January 2021, researchers from Ruhr-Universität Bochum made headlines after publishing in Nature Communications that they had succeeded for the first time in enabling formerly paralyzed mice to walk. They had accomplished the feat by using gene therapy to transfer the gene for hyper-interleukin-6, a so-called designer cytokine, which does not occur in nature, to the brain of the animals. The gene was packed into Adeno-Associated Viruses (AAV) and the vector injected into the brain, where motoneurons and associated motion-related nerve cells started to produce this growth factor.

“Thus, gene therapy treatment of only a few cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” said Dietmar Fischer, Professor at the Department for Cell Physiology at Ruhr-Universität Bochum and lead author of the study. “Ultimately, this enabled the previously paralyzed animals to start walking after two to three weeks. This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia.”

The development of gene therapy

This breakthrough, which might end paraplegia in injured humans, is just one of many successes accomplished with gene therapy. The approach has come a long way. Its basic concept – modifying human genes by introducing genetic material – was first proposed in 1972. After premature first attempts in the 1980s failed, the science greatly improved and in 2003 China took the lead by approving Gendicine, a recombinant Ad-p53 gene therapy for the treatment of head and neck squamous cell carcinoma (HNSCC)—a cancer that accounts for about 10% of the 2.5 million annual new cancer patients in China.

It took another 9 years until the EU followed with the approval of Glybera, a treatment for patients who cannot produce enough of an enzyme that is crucial for breaking down fat, and in 2017 the first gene therapies were approved in the U.S.: Luxturna to treat RPE65 mutation-induced blindness and Kymriah, a therapy for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses genetically engineered T cells of the affected patients. Since then, further gene therapies have been approved, e.g. Zolgensma and Patisiran, and hundreds of clinical trials are under way to test gene therapy as a treatment for genetic disorders, cancer, and HIV/AIDS.

The gene therapy market was valued at approx. $ 500 m in 2018 but is expected to reach > $ 5 bn by 2025 with an impressive CAGR of about 34%.

How does gene therapy work?

Gene therapies can work through several mechanisms, the replacement of a disease-causing gene with a healthy copy, inactivation of a disease-causing gene that is not functioning properly and the introduction of a new or modified gene into the body to help treat a disease. The latter approach was used in the study to heal paraplegic mice.

There are various methods for administering gene therapeutics. The most common approaches are the use of viral vectors (mostly AAVs and lentiviruses) to transfer the genes directly to the patient, or the modification of patient-derived cells in the lab with subsequent transfer of the modified cells back into the patient. Most approaches use performing gene insertions in vivo and ex vivo, respectively, but non-viral delivery systems are also being used.

Evotec´s gene therapy strategy

Evotec entered the gene therapy space in 2020 by establishing an alliance with Takeda, adding a team of 20 specialists by creating Evotec GT in Austria, where Takeda’s gene therapy operation GTCA (Gene Therapy Center Austria) is located.

Evotec GT is now an integral part of Evotec’s integrated drug discovery platform. Its services include

  • the design of state-of-the-art viral AAV vectors,
  • the generation of AAV material for research and non-clinical studies, 
  • in vitroand in vivo proof of concept studies for target validation including screening of drug candidates, as well as
  • the design, execution and interpretation of non-clinical gene therapy studies.

The services cover both in vivo and ex vivo gene therapy approaches. With this new unit, Evotec is now able to find the best potential drug candidate agnostic of modality for any given biology.