Cell and Gene Therapy and ATMPs

Advanced therapy refers to new medical products that use:

  • Gene therapy
  • Cell therapy
  • Tissue engineering.

They can be used to treat diseases or injuries, such as skin in burns victims, Alzheimer’s,

and cancer or muscular dystrophy, and have huge potential for the future of medicine.

Gene Therapy:

The ability to make local modificiations in the human genome has been the objective of Medicine since the knowledge of DNA as the basic unit of heredity. Gene therapy is understood as the capacity for gene improvement by means of the correction of altered (mutated) genes or site-specific modifications that have therapeutic treatment as target. Further on, diffrent strategies are described, which are often used for this purpose.

Currently, gene therapy is an area that exists predominantly in research laboratories, and its application is still experimental. Most trials are conducted in the United States, Europe, and Australia. The approach is broad, with potential treatment of diseases caused by recessive gene disorders (cystic fibrosis, hemophilia, muscular dystrophy, and sickle cell anemia), acquired genetic diseases such as cancer, and certain viral infections, such as AIDS.

Cell Therapy:

Cell therapy (also called cellular therapy or cytotherapy) is therapy in which cellular material is injected, grafted or implanted into a patient; this generally means intact, living cells. For example, T cells capable of fighting cancer cells via cell-mediated immunity may be injected in the course of immunotherapy.

Tissue Engineering:

Body tissues and organs have both structure and function, and therefore, any engineered material must be able to recapitulate the morphology and characteristics of the target tissue and organ. Several methods have been used to combine both structure and function in engineered tissue or organs. Decellularization of tissues and organs and recellularization before transplantation have shown great promise as they remove immunogenic cells whilst maintaining the structure and material composition of the native extracellular matrix.

Advanced Therapy Medicinal Products (ATMPs):

Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer groundbreaking new opportunities for the treatment of disease and injury.

ATMPs can be classified into three main types:

  1. Gene therapy medicines:These contain genes that lead to a therapeutic, prophylactic or diagnostic effect. They work by inserting ‘recombinant’ genes into the body, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases. A recombinant gene is a stretch of DNA that is created in the laboratory, bringing together DNA from different sources;
  2. Somatic-cell therapy medicines:These contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. They can be used to cure, diagnose or prevent diseases.
  3. Tissue-engineered medicines:These contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue;

In addition, some ATMPs may contain one or more medical devices as an integral part of the medicine, which are referred to as combined ATMPs. An example of this is cells embedded in a biodegradable matrix or scaffold.

In recent decades, genes, cells and tissues have been adapted as new therapeutic tools in medicine. In this new approach, known as advanced therapies, each of these therapeutic agents is termed an advanced therapy medicinal product (ATMP).  As in other medicinal products such as drugs, devices and biological agents, products based on genes, cells and tissues are subject to regulatory requirements that vary widely among countries and product types.

Advanced therapy medicinal products (ATMPs), which include gene therapy medicinal products, somatic cell therapy medicinal products and tissue-engineered products, are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. They have therefore been subject to considerable interest and debate. Following the European regulation on ATMPs, a consolidated regulatory framework for these innovative medicines has recently been established. Central to this framework is the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), comprising a multidisciplinary scientific expert committee, representing all EU member states and European Free Trade Association countries, as well as patient and medical associations. In this article, the CAT discusses some of the typical issues raised by developers of ATMPs, and highlights the opportunities for such companies and research groups to approach the EMA and the CAT as a regulatory advisor during development

Development of Advanced Therapies:

The commercial development of advanced therapy medicinal products (ATMPs) represents great opportunity for therapeutic innovation but is beset by many challenges for its developers. Although the ATMP field continues to progress at a rapid pace, evidenced by the increasing number of clinical trials conducted over the past few years, several factors continue to complicate the introduction of ATMPs as a curative treatment for multiple disease types, by blocking their translational pathway from research to the patient. Innovative Medicines Initiative consultation has highlighted the major gaps in ATMP development, with manufacturing, regulatory, and reimbursement issues at the forefront, there remains to be formulated a coherent strategy to address these by bringing the relevant stakeholders to a single forum, whose task it would be to design and execute a delta plan to alleviate the most pressing bottlenecks. This article focuses on two of the most urgent areas in need of attention in ATMP development, namely manufacturing and reimbursement, and promotes the concept of innovation-dedicated research infrastructures to support a multi-sector approach for ensuring the successful development, entry, and ensuing survival of ATMPs in the healthcare market.

Current Challenges in Advanced Therapy Development

The relative dearth of industrial investment in the ATMP space arguably lies behind the manifold bottlenecks in the ATMP space, especially more downstream aspects, such as manufacturing, control, distribution, and the various market-related challenges. The issues are numerous but main issues are distribution, manufacturing, and reimbursement.

Advancements in biomedical sciences are leading to new treatment options for disease with high unmet medical need and create possibilities to improve the quality of life in aging populations. Medicines derived through these advancements include genetic therapy medicinal products (GTMPs), cell-based therapy medicinal products (CTMPs), tissue-engineered products (TEPs), and products integrally combined with medical devices, in Europe known as advanced therapy medicinal products (ATMPs).