Dr Ruth Standring-Cox BSc DPhil explains about her link with MND and her research experience, including how research has moved on in the past 40 years.
After successfully negotiating the “paternoster lifts” in the old Biochemistry building at Oxford University I reached the MRC Immunochemistry Unit on the 4th floor. This was 1975 and the start of my three year DPhil research project.
The basics of immunology
I quickly realised that we had only been taught the basics of the immune system during my biochemistry degree. I knew that lymphocytes are white blood cells with important roles in the body’s defence mechanism and there are two primary types, B lymphocytes (B-cells) and T lymphocytes (T-cells), both originating from haematopoietic (blood forming) stem cells in the bone marrow.
An antigen is a substance which the body regards as foreign (e.g. a bacterium or chemical) and triggers an immune response. An antibody is a highly specific Y shaped protein made by B-cells in response to an antigen. Some antibodies destroy antigens directly while others make it easier for white blood cells to destroy the antigen, in the case of a bacterium preventing it from causing disease.
Now, I was thrown into the complex and exciting world of immunology!
Research in our unit and collaborations: antigens and antibodies
In certain circumstances T-cell surface proteins can be antigens. For example, if these T-cell surface proteins are injected into a different species (e.g. rabbits), antibodies will be produced. Our team used antibodies as tools to investigate the structure and function of cell surface antigens on T-cells.
Initially we used polyclonal antibodies. Polyclonal antibodies are simply a number of different antibodies that have been made by several different B-cells, which bind to many different T-cell surface antigens. However, in 1976 my supervisor Alan Williams started a collaboration with César Milstein in Cambridge to use monoclonal antibodies. Monoclonal antibodies are produced from a single clone of B-cells and are specific for only one T-cell surface antigen. Monoclonal antibodies work by binding to the same part (known as an ‘epitope’) on that specific T-cell surface antigen.
Proteins on the surface of human cells and tissues can be seen as antigens when transferred from one human into another. For example, donor red blood cells, typed according to the ABO system, need to be the same blood group as those of the recipient. To minimise the risk of rejection after transplantation the cells (e.g. haematopoietic stem cells) and tissues (e.g. liver) transferred from the donor to the recipient should be matched according to the human leukocyte antigen (HLA) system.
I move on: uses for monoclonal antibodies expand
On completion of my DPhil I moved into research within the pharmaceutical industry working on proteins for use in medical therapies and cell culture systems. During this time period (1978-95) monoclonal antibodies became available as diagnostic tools e.g. for routine use in ABO blood typing, and could be produced on a large commercial scale.
Another important development was their use in the purification of natural products for medical therapies e.g. human leukocyte interferon (this is released in response to pathogens such as bacteria, viruses or parasites).
Genetic engineering radically transformed the process for making monoclonal antibodies and increased the potential for use in medical therapy. Haematopoietic stem cells extracted from the bone marrow (by drilling into the bone) of one sibling had been successfully transplanted into another sibling with a dampened immune system (known as immunodeficiency). Techniques were developed for artificially releasing stem cells from the bone marrow into the blood and harvesting the resultant peripheral blood stem cells (PBSC). Advances in HLA typing improved the chances of success in the transplantation of PBSC from any matched donor to treat patients with, for example, immunodeficiency and various types of leukaemia.
My lab days end: monoclonal antibodies as medical products
In 1995 I hung up my lab coat and started work in regulatory affairs. This involved liaison between companies and regulatory agencies during clinical trials and, once a medicine was proven to be effective and safe, managing the process to obtain an authorisation to market the product. Monoclonal antibodies have now been proven to be effective medical therapies for various conditions, e.g. cancers, autoimmune diseases, and have gained marketing authorisations in the European Union (EU) and worldwide.
Regulation of human PBSC’s, other cells and tissues also evolved. Under the UK Human Tissue Act 2004 and EU Tissues and Cells Directive 2007 all cell banks have to be licensed. During my 5 months (2007-8) working for the Human Tissue Authority I was involved in the inspection of UK cell banks. UK cell banks have to meet the standards for procurement, testing, processing, storage and distribution of cells for human application. Consent from donors must also be obtained and documented.
The present and the future
Here we are in 2014 and I have retired. However, I am still enthusiastic about medical research. In addition to the bone marrow, stem cells can be found in various tissues in adults where they act as a repair system for the body. These are termed adult stem cells.
Cells from adult skin can be reprogrammed to become stem cells and then induced to become any type of cell, including motor neurones. These are termed induced pluripotent stem cells (iPSCs). You can read about the Association’s iPSCs research here.
Any cells or tissues that have been manipulated to change their biological characteristics or have been modified so they can be used to repair, regenerate or replace tissue are regulated as Advanced Therapies by the European Medicines Agency. No medicines based on stem cells have yet received a marketing authorisation in the European Union.
Research and potential therapies for MND are very close to my heart as my mother-in-law died from MND in 1993. I am looking forward to developments in both the diagnosis (aided by the discovery of biomarkers) and possible therapies. However, I know from experience that I must be patient as the road from research to a therapy is both long and rocky.
