Infection Cures Infection
In the world today, there are hundreds of diseases that exist and have no cure till date. Out of these, many are instantly terminal. They continue to concern different groups of the population and manifest particular symptoms and effects.
Severe Combined Immunodeficiency, commonly known as SCID, is a group of rare congenital syndromes with little or no immune responses which leads to repeated infections with bacteria, fungi, and viruses. A major defect in T cell development and function is often a distinguishing feature of SCID, with faults in B-lymphocytes as a primary or secondary issue and, in certain genetic forms, even in the development of NK cells.
T lymphocytes are a component of the immune system and originate in the bone marrow from stem cells. They assist in protecting the body against infection and can help combat cancer whereas, B lymphocytes are a type of white blood cells which make antibodies. This defect in the immune system weakens it greatly. Infants with SCID die of weak immunity by age 2 unless they receive the required and prescribed treatment.
The disease is inherited, and the most frequent types are X-linked and ADA deficiency. Symptoms of the diseases range from minute infections to life-threatening illnesses. The infections cannot be treated easily due to the lack of an immune system and medicines often fail to work well. Pneumonia, hepatitis, Chronic Skin Infections, meningitis, repeated ear infections and diarrhoea are some common illnesses that could occur.
There is no standard cure or medicine for SCID however, long term treatment includes bone marrow transplants and gene therapy which have their own success statistics and work differently in different children. While the aforementioned techniques are standard and well known, a recent clinical trial revealed the use of the HIV virus in the treatment of SCID for the alleviation of the immune system.
An infectious diseases, AIDS which is otherwise known to weaken the immune system, is noted curing another immunodeficiency disease. And while that sounds absurd, the clinical trial has indicated various successes along with multiple shortcomings.
What Is The Bubble Boy Syndrome?
Also known as SCID or Severe Combined Immunodeficiency Syndrome, the disease is caused by an abnormality in the IL2RG gene. Affected are born with a hardly effective immune system which indicates that even something as normal as a common cold can be a fatal occurrence. The only way to protect the patients with SCID from infections and fatal conditions is by confining them to a high-tech sterile room
Pre-Existing Scid Treatment Options
About 1 infant in every 50000 live births is diagnosed with SCID and is detected in new-born screening or blood tests. Infants with SCID are not only at high risk of morbidity but also of death in the first two years of life itself. However, with specific treatment plans, a normal life can be expected.
The two most prominent treatment options are as follows:
1. Bone Marrow Transplant: A bone marrow transplant or stem cell transplant is perhaps the most common treatment for SCID. The patient acquires a compatible donor who is typically a sibling and then receives healthy stem cells during the procedure. The newly acquired cells are responsible for reconstructing the immune system of the SCID positive infant.
Children undergoing this treatment are expected to be cured however, unfortunately, statistics show that such a donor is only available in about less than 25% patients with SCID. In the absence of a sibling, physicians may use stem cells from an unrelated donor or a parent. A bone marrow transplant works well only in the early years of life thereby, stressing on the importance of an early diagnosis. This could be potentially dangerous in case it fails to improve immunity as in that case it could result in irreversible organ damage.
2. Gene Therapy: Some of the patient’s bone marrow stem cells are extracted in this procedure and a corrected copy of the gene mutation is introduced into the stem cells of the child’s own bone marrow. Such cells are transplanted into the body of the patient and help stabilise the immune system.
One drawback with gene therapy is that genes which are next to the site of injection might become cancerous after introducing a gene into the DNA of people, as occurred in previous places where people developed leukaemia. Nevertheless, by including “insulator” genes that practically obstruct the activity of the neighbouring genes to keep them from becoming cancerous, the new therapy can successfully prevent this from occurring.
What Is HIV And AIDS?
The Human Immunodeficiency virus or the HIV virus is a virus that attacks and destroys T white blood cells or immune cells called the CD4 cells. They obstruct their function which is to identify body-wide infections and abnormalities in order to prevent them from growing. The HIV not only destabilises the CD4 cells but also uses them to multiply the virus copies. By doing so, it decreases the capacity of the body and reduces immunity to diseases and infections leaving the human body prone to a number of conditions.
In case a person infected with the HIV virus does not receive the required treatment then the immune system continues to ware down while a condition called Acquired Immunodeficiency Syndrome or AIDS is developed. This is an advanced stage of HIV infection.
The ability of the body to battle a variety of infections and related illnesses and cancer types is decreased by late-stage HIV. Available treatment is also sufficiently effective at keeping many diseases at bay. Malignant infections that once posed little or no health complications may pose a serious threat if a person with HIV does not seek treatment. Physicians refer to these diseases as being opportunistic.
The Link Between HIV and SCID
The link between the two seemingly unrelated diseases lies in the involvement of T cells or immune cells present in the immune system of human beings. Whereas the HIV virus invades T cells and destroys them, the SCID causes a major defect in T cell development and function. Let us explore more about how they are associated for effective treatment of one disease from a virus causing another disease.
Latest Gene Therapy Modification
X-SCID is an inherited disease where the cells essential for guarding against infection cannot be produced by the body: T-cells, B-cells, and natural killer ( NK ) cells. The condition is uncommon, but catastrophic. Kids born with SCID submit to infections without treatment and perish by the age of two. Around 30 percent of all those undertaking a stem cell transplant, the best-available option, die before age 10.
Researchers at the St Jude Children’s Research Hospital and the University of California, San Francisco conducted a clinical trial to better develop the immunity for patient with SCID.
The procedure includes extracting the patient’s own blood stem cells out of their bone marrow and then genetically adjusting them to rectify the SCID-causing genetic mutation.
Small doses of chemotherapy are then administered to patients to build space for new cells in their bone marrow. The stem cells that are mutation-corrected are then transplanted back into the child, making a new source of blood and a strengthened immune system.
The following is the step by step process carried out during the trial which helped cure about 10 children with the bubble boy disease in US.
Scientists develop a gene to correct the DNA in kids with SCID-X1
The HIV virus is modified and inactivated in a way that it can no more infect the patient’s cells. After which it is attached to the new gene.
The DNA is replaced with corrected genes as the inactivated HIV virus is injected into the patient’s body.
The HIV virus then self-destructs and the corrected DNA begins to self-replicate.
The replicated DNA spreads throughout the body and reprograms the immune system to produce healthy levels of T lymphocytes.
The immune system of the infant is thus boosted and the irregularity of the T lymphocytes is eliminated.
Up till now, in seven children, researchers have examined their latest gene therapy, monitoring results for up to 12 months. In a few of the monitored infants, early findings show proof of T-cell, B-cell, and NK cell development, with no adverse side effects. In all blood cell types, exceedingly high levels of the gene were seen, but in other cases, the corrective gene for X-SCID was found in more than 60% of all bone marrow stem cells. So far, all of the handled babies seem to be doing well and better than what other treatment options could possibly do.
“It is very exciting that we observed restoration of all three very important cell types in the immune system,” said lead study author Ewelina Mamcarz, MD, assistant professor in the bone marrow transplant department at St. Jude Children’s Research Hospital.
Conclusion
A potentially life-threatening disease, SCID treated by HIV, the virus that causes AIDS and which has affected more than 35 million people globally. It is, indeed, impossible to imagine that the same technique used by the virus to infect cells which kill thousands across the world could then be used to help children overcome a deadly immunological disorder. However, this has been made possibly by a group of talented researchers at the St Jude Hospital for Children.
The treatment for any disease depends on the specific condition and requirements of the patient. Similarly, for SCID, there are two known types of treatments that exist, being a bone marrow transplant and gene therapy. While both have proven to be effective at different points in time, each has its own drawback. While stem cell transplants are not always possible due to the lack of a perfectly compatible donor and post-operative risks attached, gene therapy could also have several side effects. The latest development in gene therapy which involves the use of inactivated HIV to infiltrate the cells and revamp the immune system has proven to be a safer alternative than the already existing methods. The linkage between the two has been strategically handled to provide a better cure for the fatal disease.
There are various different types of mutations that can cause SCID. The new approach has been designed and used for those with the X-linked SCID however, researchers say and are confident that the approach can be modified to cure not only SCID linked to other genetic mutations but also other genetic disorders.
Claiming the innocent lives of thousands each year, the above discussed gene therapy for Severe Combined Immunodeficiency could prove to be a sigh of relief for parents and extraordinarily beneficial to patients and doctors all across the globe. With increased newborn screening and early cost-effective treatment, awareness and availability, the fatal issue of SCID could be resolved using the fatal Human Immunodeficiency Virus.
Citations
1. Rare Diseases
https://rarediseases.org/rare-diseases/severe-combined-immunodeficiency/
2. Cancer.gov
3. Stanford Children
4. St Jude
https://www.stjude.org/disease/severe-combined-immunodeficiency-scid.html
5. Medical News Today
https://www.medicalnewstoday.com/articles/17131#prevention
6. Blog- California Institute for Regenerative Medicine
7. Eurekalert
https://www.eurekalert.org/pub_releases/2017-12/asoh-bs120917.php
8. Live Science
https://www.livescience.com/65270-bubble-boy-disease-gene-therapy.html
