Introduction
Stem cell therapy has proved to be a boon for the medical world. It has made treatment of many diseases a lot easier than it could have been ever imagined. Diseases which were earlier considered untreatable can now be treated with the help of this latest development in the field of Medical Science, known as the stem cell transplant. Many medical researchers believe that stem cell transplant have enormous potential to change the face of disease among the humans and relieve them from their sufferings. There already are a good number of stem cell treatments existing in the medical world. However, they are not so commonly used. The reason for the less utilisation of these therapies could be that they are still under the experimental phases and are not very cost effective. But in future, it has been anticipated by the medical researchers that they will be able to use this technology and treat diseases like cancer, muscular damage, injuries of the spinal cord and many more immunological diseases (ScienceDaily, 2016). In this paper, we will discuss an important disease known as the Severe Combined Immunodeficiency Disease (SCID). We will discuss the role of stem cell therapy in the treatment of this disease. We will try to investigate the developments that have been evident in the treatment of the disease SCID with the help of stem cell therapy. The diagnosis of the disease SCID consists of clinical examinations of the patient. Investigations regarding the total lymphocyte count can be extremely helpful. Lymphocyte count below the normal levels is somewhat indicative of the disease condition. Prenatal screening can prove to be the best form of diagnosis as screening test done at an early stage can help in the early diagnosis and thus, help in managing the disease condition as soon as possible. The treatment procedures usually consist of keeping the child away from germ rich environment and from too much of crowded places. Stem cell therapy is considered as the best form of treatment nowadays, however in earlier times the treatment consisted of injections of Adenosine deaminase. With progress in the Science and Technology, the use of stem cell therapy has proved to be a boon for the patients of this disease. In order to understand the implication of the treatment procedure in this disease, we must have a thorough knowledge of the same.
Severe Combined Immunodeficiency Disease
Severe Combined Immunodeficiency Disease represents a group of very rare, fatal and congenital disorder which is characterized by very little of the complete absence of immune response of the body. A very important defining feature of the disease is known as the “Bubble boy” disease. It is a disease that is characterized by a defect in the special WBCs which are usually responsible for providing defensive response against infections by a virus, bacteria and fungi. In the absence of a normally working immune system the patients of this disease become highly susceptible to recurring infections like chicken pox, pneumonia, and meningitis. Most patients affected with this disease are children who die even before they complete the first year of their lives. However, new treatment options like the bone marrow and stem cell transplantation have been successfully used and have treated many patients with the disease.
All the forms of this disease are inheritable. Almost half of the disease cases are X-linked; it is thus passed on by the mothers to their children. The X- linked disease is a result of a mutation in the interleukin 2 receptor gamma gene. Interleukin 2 receptor is responsible for producing the common gamma chain subunit which is a component of several interleukin receptors. Normally, Interleukin 2 receptor gamma gene leads to activation of an important signalling molecule named as JAK3. Any mutation in the JAK3, which is located on chromosome number 19, can lead to the disease SCID. A defect in the interleukin receptors and interleukin receptor pathways prevent the development of T- Lymphocytes which are responsible for playing a major role in the identification process of the invading agent. They are also responsible for regulating other cells of the immune system.
(Severe Combined Immunodeficiency, 2016)
In some other forms of SICD, there is an absence of an enzyme known as adenosine deaminase. This enzyme is coded for by a gene on the chromosome number 20. This thus ultimately leads to the accumulation of substrate for this enzyme in the cells. the immaturity of the lymphoid cells of the immune system of the body is extremely sensitive to the toxicity developed from these unused substrates. The cells thus fail to reach the level of maturity. The immune mechanism of the affected patients is seriously damaged and is highly lacking in function (Severe combined immunodeficiency, 1998).
Dr. Rebecca Buckley says that the disease which was once considered a fatal one can now be called a case of paediatric emergency. Early diagnosis of the disease is not that common because most of the states do not perform the screening test among the newborns for this disease, hence, it becomes difficult to diagnose the disease at an early stage. The newborn screening heel stick test can help in diagnosing the children with this disease. This test can help in an early diagnosis and timely treatment of the disease. If diagnosed at an early stage, the cost of treatment can be controlled; however, a timely diagnosis will add up to the cost of treatment. Buckley also says that every child who is born with this disease can be treated and cured if the diagnosis is done at a relatively early stage and thus, the disease should be considered as a paediatric emergency rather than a fatal one.
As discussed earlier in the paper, the disease is also known as bubble boy disease. The name has come into existence during the period of 1970 and 80. A boy named David Vetter had X- linked SCID. He lived till the age of 12 years in a plastic bubble which was completely sterilised (Severe Combined Immunodeficiency, 2016). The disease usually manifests itself in a number of infections affecting almost any system or organ of the body. It may include diseases like recurrent infections, fatal pneumonia, infections of the lungs brain and liver. It may also lead to diseases like mumps, rubella, or other fungal infections which may become very difficult to treat. Recurrent diarrhoea resulting in failure to thrive may seem to be a common problem in most of the children with this disease. Some children may even show skin manifestations. Their skin may develop chronic infections with candida leading to thrush.
Clinical diagnosis may be done based on the symptoms of the disease as discussed above. However, in some cases, the diagnosis can be done depending on the fact that previously there has been a child in the family suffering from the same disease. The positive family history points towards the certainty of the diagnosis. In some particular States, the screening of the disease is done on every newborn child. The easiest diagnostic test for the disease is counting the peripheral blood lymphocytes of the child. It can be done by two methods; they are complete blood count followed by the manual differential. With the help of this differential, the Healthcare professionals can calculate the exact number of lymphocytes. Usually, there is more than 4000 lymphocytes in a normal newborn blood sample within the first few months of life. Out of these more than half are T- cell. As infants with this disease lack T- cells, they present with much fewer lymphocytes than those with a normal count. On an average, the lymphocyte count of a patient with this disease is 1500 only. If the lymphocyte count is found to be low on repeated tests then the diagnosis becomes almost certain.
The general treatment of the disease begins with love and support of the parents as the disease may prove to be fatal. It is important to nurture the child and give him all the love and support that he may need during the disease phase. The parents may need to be counselled regarding the anxiety and stress that they might be facing because of the extremely devastating situation. Unless a definite treatment like stem cell transplantation has been considered, the Infant with the disease should be kept isolated from children not belonging to their families (Immune Deficiency Foundation, 2016).
As far as the treatment for this disease is concerned the initial line of treatment should begin with keeping the children away from germ rich environments like a crowded marketplace or any day care centre. Being in a crowded place, the children become more vulnerable and get more exposure to life-threatening infections. The best possible treatment for this disease is bone marrow transplantation. Some specialised stem cells are first isolated from the bone marrow of a healthy donor. These are then injected into the patient. These new cells help in the stimulation of the immune system and leads to the production of the required cells. Transplant which is carried out within the first few months of the life is highly successful. The prerequisite for carrying out the transplant is that the tissue must match with that of the patient. Siblings of the patients are the best donors because the cells of the siblings usually have a very similar genetic makeup. Gene therapy can also be considered as an effective treatment option. Gene therapy will compensate for the damaged genes by giving an injection of a healthy copy of the gene into the patient's bone marrow stem cells (Learn.genetics.utah.edu, 2016).
Stem Cell Therapy and SCID
In the past, the treatment for SCID consisted of a series of injections. The patients with SCID were injected with Adenosine Deaminase (ADA) (the enzyme that the patients of SCID were lacking in). This treatment option was not a feasible one. Lifelong injections of ADA were a costly affair. On the other hand, it did not restore the immune levels of the patient back to their normal optimal levels (Bracke, 2014). It was, therefore, important to discover new methods which will not only be feasible but will also prove to be highly effective.
(Induced Pluripotent Stem Cells, 2016)
In the year 2009, Kohn and his team of research experts devised a new method for the treatment of SCID. The blood stem cells of the children affected with the disease were extracted from their bone marrow. It was then genetically modified and the defect was corrected. The reinsertion of the blood stem cells was done with the help of a virus delivery system. The modified stem cell then becomes capable of producing T- lymphocytes. But the efficacy of the virus delivery system was questionable. Various researchers from different parts of the world have proved the efficiency of gene therapy for the treatment of various forms of SCID, they also aimed at verifying the efficacy of the virus delivery system. With the help of gene corrected autologous stem cells, excellent results can be obtained in the treatment of SCID. Two trials have shown the clinical utility of introducing therapeutic gene in hematopoietic cells. Both the trials have been extremely successful. They showed long-lasting restoration of immunity and lymphocyte development was back to normal. However, development of leukaemia appeared to be an adverse reaction in both the trials. In 5 cases reported in the trials, T- cell acute lymphoblastic leukaemia has developed as a direct result of insertional mutagenesis in the retroviral vector, which was used to deliver the therapeutic gene. However, such effects have not been seen in any of the Italian patients with whom the trial was conducted. In one of the German trials using similar technology, a similar adverse effect resulting from insertion mutagenesis has been seen (Mikkers, Pike-Overzet and Staal, 2012).
Transplants are more successful and provide a better result when done at an early stage, possibly within the first few months of life. There are certain conditions when transplants can be more fruitful; the child should not suffer from a major infection until the time of transplant operation; the child should not have shown failure to thrive; and the child should have the type of SCID where he has normal B cell functioning (National Marrow Donor Program (US), 2016).
Both the new forms and the old treatment forms have their own merits and demerits. The older method of injecting ADA was free from any side effects but was not as effective as it should have been or as much as required. Its inefficacy called for a newer and better method to be adopted. The newer method of stem cell transplantation has brought about immense success in the treatment of SCID but has also led to the development of many side effects. The use of vectors has resulted in the development of leukemia in many patients. Therefore, more research s required before stem cell transplantation can be declared as the best method of treatment of SCID. An ideal treatment method should be highly effective and completely free of life threatening side effects.
Conclusion
The disease SCID has affected many children across the globe. The complexity in the symptoms calls for a treatment procedure which enacts at the root cause of the disease, which is, increasing the lymphocyte count of the patient. Initially, injecting the deficient enzyme, ADA was considered an effective treatment method. But it had many shortcomings. The treatment neither brought about any significant increase in the number of lymphocytes, nor did it lower the rate of infections among the patients of SCID. It thus, urged the medical researchers to devise a better method for treating the disease condition. Multiple researches led to the invention of stem cell therapy as a method to treat SCID. Stem cell therapy has proved to be a boon for the treatment of SCID. But it results in the development of serious side effects like leukaemia. It requires further research in order to combat the adverse effects that may appear as side effects of the treatment procedure. If the treatment comes along with a side effect that may prove to be fatal for the patient, then the whole aim of treatment stands futile and the efforts go in vain. Therefore, the stem cell therapy needs to be worked upon in order to remove the resulting side effects. Further developments in the field of science and technology will certainly aid in curing the disease without any side effects in the near future.
References
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