Stem cell transplant trial for early MS sufferers yields promising results
Multiple sclerosis (MS) is caused by the destruction of the Schwann cells, which form the fatty myelin sheath surrounding nerves, by the cells of the immune system. This autoimmune disease affects about 85,000 people in the UK and a million people worldwide, making it the most common disabling neurological disorder currently affecting young adults.
In MS the white cells of a person’s immune system wrongfully attack and destroy normal cells of the body. They are able to cross the protective blood-brain barrier, and attack the protective fatty sheaths of the brain's neurons. The destruction of the fat layers causes incorrect transmission of nerve impulses between neurons, which manifest as physical symptoms of fatigue, muscle weakness and spasms, difficulties with eyesight, speech, and swallowing, and depression. Sufferers usually begin by entering a relapsing-remitting phase of 10-15 years, during which they experience periods of symptoms followed by apparent recovery. However, as the disease progresses into the secondary and primary phase, the individual experiences worsening symptoms with no remission. Currently, there is no cure.
Experimental autoimmune encephalitis
To develop treatments for MS, researchers use experimental autoimmune encephalomyelitis (EAE) mice, first described 50 years ago as a highly important model of inflammatory CNS autoimmune disease. Using this model, researchers can produce acute, chronic, and relapsing-remitting EAE models to trial MS treatment. The model also study of the disease‘s nature . Like other autoimmune diseases, it is thought that MS can be induced by a viral infection. This theory has been supported by animal studies, and makes the EAE model especially suitable as the condition caused by a virus. Revealing the cause of the disease may help us to understand its transmission and early development, as well as improving the efficacy of treatment.
Stem cells and transplants
An emerging potential treatment is to actually remove these ‘self-reactive’ lymphocytes, and replace them with lymphocytes developed from the patient’s own stem cells. In effect, this is a recalibration of the person’s immune system which removes the abnormal aspects and transplants their own immune cells back into the body. Because the replenishing white cells are developed from the patient’s own stem cells, they do not induce the usual problems of rejection .
In a study published in the Lancet, researchers recruited 21 sufferers in the relapsing-remitting phase of MS who had not responded to traditional treatment. They used a low-intensity treatment to remove the patients’ self-reactive white cells. New white cells were developed from stem cells taken from the patient’s bone marrow, and transplanted back into the body. After an average period of 3 years, 81% of patients showed improvement of physical disabilities, and 100% showed disease stabilisation.
The use of HSCT (Hematopoietic stem cell transplantation) to treat autoimmune disorders was first considered following observations of autoimmune disease remission when bone marrow tissue was destroyed during cancer therapy. As researchers found that bone marrow transplants could induce either resistance or susceptibility to autoimmune diseases , and realised that the bone marrow cells were key to the development of such diseases. However, the destruction of bone marrow was an aggressive treatment regime which severely depleted the patient’s immune system. Using the animal model, researchers were able to conclude that bone marrow transplants were a viable treatment for MS, but that severe depletion of lymphocytes also raised the mortality risk . These results led to the development of less aggressive conditioning regimes which would be safer for human patients.
Comparing animal and human study results has revealed that human autoimmune diseases are caused by multiple underlying factors. Animal models have shown genetic factors to be strongly influential, whereas in humans, it is suggested that environmental factors may be key to the development of the disease. Researchers are also using animal models to further investigate whether the source of the HSCT should be the individual concerned, or a donor.
Future research will focus on assessing the latest breakthrough treatment further in a larger, randomized study of 100 human volunteers, and the intensity of the immunosuppression required to reduce risks of secondary infections. Professor Richard Burt, the leader of the study, said this treatment was not a cure, but a way of "changing the natural history of the disease", while Dr Doug Brown, Research Manager at the MS Society, hailed the results as ‘encouraging’ and said- “Stem cells are showing more and more potential in the treatment of MS and the challenge we now face is proving their effectiveness in trials involving large numbers of people.”.
[1.] Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 2009; published online January 30.
[2.] Burt RK, Traynor AE. Hematopoietic stem cell transplantation: a new therapy for autoimmune disease. Oncologist. 1999;4(1):77-83
[3.] Sykes M, Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature. 2005 Jun 2;435(7042):620-7. Review.
[4.] MS Society, 2009. Stem cell therapy may halt and even reverse disability in people with relapsing remitting MS. (Research News) [Online] (Updated 30 Jan 09). Available at: http://www.mssociety.org.uk/research/news_in_research/research_news/stem_cell_trial.html
Animation explaining treatment of MS using stem cells: http://www.sumanasinc.com/webcontent/animations/content/nmss_stemcells.htmlGeneral information about stem cells and areas of researchhttp://www.explorestemcells.co.uk/
[Originally published at http://www.animalresearch.info/es/avances-medicos/23/multiple-sclerosis/#drugs]