‘Do the potential benefits of stem cell research outweigh the risks and negative ethical implications associated with it?’
1. INTRODUCTION Stem cell research is currently one of the biggest fields in modern day science. It has numerous benefits currently, and it is only the beginning. The possibilities are endless, but there are many ethical implications associated with it, as well as many risks. Do the potential benefits outweigh these risks and negative ethical implications?
2. OVERVIEW OF STEM CELLS 2.1 DEFINITION OF STEM CELLS
Stem cells are unspecialised cells which are able to become any type of cell in the body. They have the ability to divide and renew themselves for very long periods before they are specialised. The process in which they are changed into a specific type of cell is called differentiation. They can become cells of the heart, bones, muscles, brain, blood, skin, or any other type of cell. There are different types and sources of stem cells, but they all have the ability to develop into different types of cells.
2.2 TYPES OF STEM CELLS
2.2.1 EMBRYONIC STEM CELLS
Embryonic stem cells are cells found in embryos during the blastocyst stage. They are obtained from the eggs of an infertile couple, that are fertilised in vitro, rather than in the woman’s body.
2.2.2 ADULT STEM CELLS
Adult stem cells, also known as somatic stem cells, are found in certain tissue of fully developed humans. They can produce only certain types of cells. In the body they maintain and repair tissue. They can be found in bone marrow. They can also be found in the brain, skin, liver, skeletal muscle and in blood vessels, but in small amounts.
2.2.3 AMNIOTIC STEM CELLS
Amniotic stem cells are found within the amniotic fluid. They are extremely active and can multiply without a food source. They have a limited number of cells into which they can form, but, unlike embryonic stem cells, they are unable to cause tumours.
2.2.4 INDUCED PLURIPOTENT STEMS CELLS
These stem cells are formed by genetically programming adult skin cells to become stem cells. (i)
2.3 HARVESTING OF STEM CELLS
There are different procedures followed to collect and harvest the different types of stem cells from their different sources.
Embryonic stems cells are found in embryos. Specifically, they are obtained from eggs cells from an infertile couple, that have been fertilised in vitro, rather than within the woman’s body. The embryo is in the stage of blastocyst when they are able to produce embryonic stem cells. Usually about 30 stem cells can be taken from the blastocyst.
These cells are then grown in laboratories by a process known as cell culture. The inner cell mass of the cells are removed and placed into a laboratory culture dish that contains a broth or nutrient medium, off which the stem cells will survive. The dish is often coated in mouse embryonic skin cells, known as a feeder layer, which allows the human stem cells to have a sticky surface to which they can attach. They also release nutrients into the medium within the culture dish. The dish is stored at a suitable temperature and humidity level which allows the cells to divide. The cells divide and fill the dish over several days. They are then removed and placed into several new culture dishes. This is repeated numerous times over several months and is known as subculturing. After several months, millions of stem cells can be formed from the first 30. They are then frozen in batches and sent to other laboratories for further experimentation.
Another type of stem cell harvest procedure is the removal of peripheral blood stem cells. Typically, the donor is given large doses of chemotherapy, which causes a lot of white blood cells to die. The bone marrow is then forced to try and replace it. There is not enough space in your bones for all the extra blood, so the bone marrow forces large amounts of stem cells into the blood where they are able to mature. The donor, if they do not require chemotherapy, could be given a white blood cell growth factor known as G-CSF, which has the same effect. If the donor is the same person as the patient, they will use both methods to increase the harvest.
When the stem cells are being harvested, the donor has an IV in both arms. The one extracts blood which contains the stem cells. The stem cells are extracted from the blood, and the blood is returned to the donor through the other IV. This can be used in the treatment of leukaemia. In a study involving around 38000 people, people who received treatment showed an increase survival rate from 48 to 63 percent one year after treatment. (ii)
2.4 HOW STEM CELLS WORK
Stem cells have the ability to become any type of cell in the body. They can be used in treating several types of diseases. Stem cells work by being a source of new cells to replace defective, damaged or diseased cells.
Stem cells are unspecialised cells, which form into specialised cells during a process called differentiation. Internal as well as external signals can cause stem cell differentiation. Internal signals come from within the nucleus, while external signals are caused by things such as contact with chemicals or other cells, as well as the presence of certain things in the environment.
Stem cells in culture dishes are stimulated to differentiate into differentiated cells by changing the culture broth or medium, as well as the coating of the dish. Genes are also inserted.
The differentiated cells can then be used as they are needed, or used for experimental purposes.
2.5 BENEFITS OF STEM CELLS
2.5.1 USE OF STEM CELLS AT PRESENT
TRANSPLANTING BONE MARROW TO TREAT LEUKAEMIA
HEALING BURNS WITH SKIN GRAFTS
REPLACING DAMAGED CELLS AND TREATING DISEASES
TO STUDY THE DEVELOPMENT OF ORGANISMS AND DISEASES
TESTING NEW MEDICAL TREATMENTS
MAKING INSULIN FOR DIABETICS TO INJECT
2.5.2 USE OF STEM CELLS IN THE FUTURE
TO TREAT THINGS SUCH AS:
2.6 ETHICAL ISSUES SURROUNDING THE USE OF STEM CELLS
There are several ethical issues surrounding the use of stem cells and their research. The biggest issue is the use of an embryo. Although the embryo is fertilised in vitro and come from willing couples, there are still issues regarding the debate of whether the embryo is human or not, and whether it has rights. Some people believe that human life begins at conception, or even before this, so the embryos are human and deserve rights and protection; while others believe that life begins when you are born, when your heart first beats, or a few months after development. Some groups see the use of embryos as a form of abortion. The debate depends on one’s own personal view as to whether the embryo is human or not.
Another ethical issue many people have regards the use and creation of Human-Animal Chimeras. Chimeras are organisms that contain cells or tissues from multiple organisms. Some believe that it is ethically wrong to combine human and animal stem cells to form chimeras. They are separate organisms which should not be combined. Despite these issues, chimeras are important in forming actual therapeutic methods. Law prohibits the breeding of human-animal chimeras.
The debate between preventing and reducing human suffering versus respecting the value of human life is another issue. Stem cells have the ability to cure numerous issues, and have the potential to prevent and treat several other things; but if embryonic stem cells are used, it can be seen as destroying one human life to save another.
There are also several risks involved in stem cell research and use. It is relatively new, so the long term side effects of its use in humans is so far unknown, but they could be horrific. In tests done with rats, 20% that were injected with embryonic stem cells died of some form of tumour. (chem445stemcell, 2011)
3. MY PERSONAL VIEW Stem cell research is one of the most important fields of science in modern times. It is able to, and has the potential to cure numerous diseases, illnesses and problems found in humans. Despite this many people see it as unethical and full of risks. I believe that the potential benefits outweigh the risks and negative ethical implications associated with it.
Stem cells are unspecialised cells which are able to become any type of cell in the body. They have many current uses, and they have the potential for numerous future uses. Scientists and doctors are able to do stem cell transplants from bone marrow to treat leukaemia. Thousands of patients over the globe have successfully received this treatment which has prolonged their lives. Stem cells are also able to heal burns through skin grafts, as well as replace damaged cells and treat diseases. Stem cells allow scientists to study the growth and development patterns of both organisms and diseases, as well as provide new ways of treating the diseases. Another important feature of stem cells is their use in the production of insulin for diabetics. The insulin produced is indistinguishable from human insulin.
It is not only the current uses of stem cells that are important, but also the potential that they have. Scientists are experimenting and finding ways to use stem cells to cure diseases that were once seen as incurable, such as diabetes and Parkinson’s disease. They believe that they can find ways to cure liver failure, heart damage, cancer, brain damage, deafness, blindness, hair loss, missing teeth, and even infertility. Scientist believe that they will be able to use a patient’s own stem cells to grow new organs for transplant, which would be guaranteed to not be rejected. The possibilities are endless.
Despite their potential, stem cells raise many ethical issues, and have many risks that surround them. The use of an embryo is questioned by many people. It is believed by many that human life begins at conception, or even before this. They believe that the use of an embryo is a form of abortion, or an exploitation of their human rights. Others believe that life only begins later in pregnancy, or at birth, so they disagree with this viewpoint. The embryos are donated willingly by couples, and are fertilised in vitro.
Another issue that people have is that human tissue is combined with animal tissue to form chimeras. They are separate organisms and should not be combined to create new creatures. Additional, there is an ethical issue raised on the debate between preventing and reducing human suffering versus respecting the value of human life. Stem cells have the ability to cure numerous issues, and have the potential to prevent and treat several other things; but if embryonic stem cells are used, it can be seen as destroying one human life to save another. Some of the risks involved in stem cell research and use include that it is relatively new, so the long term side effects of its use in humans is so far unknown, but they could be horrific. In tests done with rats, 20% that were injected with embryonic stem cells died of some form of tumour.
There are numerous ethical issues raised through stem cell research, but the potential that it has in curing and preventing diseases and issues in humans greatly outweighs them. Scientists must continue researching stem cells, and finding exciting ways in which they can be used.
4. EVALUATION AS TO WHAT INFLUENCED MY DECISION I visited numerous sources with different viewpoints to allow myself to make an informed decision as to where I stand regarding stem cell research.
Regarding the use of embryonic stem cells, I believe that human life begins at conception, but the fact that the couples who donate the embryos are sterile and already have children, and that the embryos are fertilised in vitro, influenced me to believe that the use of embryonic stem cells is acceptable. In 2005, guidelines regarding the use of embryonic stem cells were laid. They urge scientists to work ethically, responsibly and sensitive in their work. They are not laws, yet they still lay the basis on which most laboratories work.
There is more than one source of stem cells, so not all stem cell related topics are surrounded by numerous ethical issues. The numerous benefits and the potential that stem cells have also influenced my decision into supporting the study and research of stem cells.
Stem cell research has the potential to save thousands of lives, and through research scientists will be able to discover and test the ways in which they can be used.
5. CONCLUSION Although there are many ethical issues surrounding the use of them cells, the potential benefits of their research greatly outweighs these issues. They have the potential to save the lives of those who thought they were unsaveable, as well as treat the untreatable. Through the right research and funding, the possibilities regarding stem cell research are endless.
6. BIBLIOGRAPHY AND REFERENCES REFERENCES
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Institute, R. P. (2013, May 28). Significantly improved survival rates for stem cell transplant recipients. Retrieved from ScienceDaily: http://www.sciencedaily.com/releases/2013/05/130528180857.htm [05-03-2014]
chem445stemcell. (2011). Risks and Disadvantages of Stem Cell Research. Retrieved from Stem Cell Research: http://chem445stemcell.webs.com/risksanddisadvantages.htm [10-03-2014]
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Wikipedia contributors. Stem cell therapy. Wikipedia, The Free Encyclopedia. 27 February 2014, Available at: http://en.wikipedia.org/w/index.php?title=Stem_cell_therapy
Neurodegenerative Diseases: Systems, Causes and Treatments
Compare the symptoms, causes and available or future treatments for Motor Neuron Disease, Spinal Muscular Atrophy and Myasthenia Gravis.
Neurodegenerative diseases are hereditary (inherited) and sporadic (acquired during a person’s life) conditions caused by progressive nervous system dysfunction (http://ec.europa.eu/health/major_chronic_diseases/diseases/brain_neurological/index_en.htm). Motor neuron disease and Spinal Muscular Atrophy (shrink) are neurodegenerative conditions that arise due to motor neurons dysfunction and Myasthenia Gravis is an autoimmune neurodegenerative disorder. Motor neuron disease is caused by damage to motor neurons; Spinal muscular atrophy is due to deterioration of the motor neurons connecting the brain and spinal cord; Myasthenia gravis is an autoimmune condition that arises due to the damage or blocking of muscle receptors by antibodies accidently produced by the immune system. All three disorders result in weakness, making there diagnosis very hard, because weakness is a very common symptom of many conditions. However, possibilities are ruled out depending on the age of the person affected. If someone exhibiting muscle weakness is 1 year old, it is more likely that the person has SMA than the MG or MND, because SMA generally affects children ranging from less than six months to around the age of three, whereas MND is common in teenagers and young adults, and MG normally affects middle aged adults.
Motor neurone disease is a unique condition of unknown aetiology that occurs when motor neurons (specialist nerve cells in the brain and spinal cord that relay signals from the brain to the muscles) become damaged and ultimately stop working (http://www.nhs.uk/conditions/Motor-neurone-disease/Pages/Introduction.aspx). This causes the muscles that the damage nerves supply to gradually lose strength, usually with wasting of muscles. It is unclear exactly what causes motor neurons to stop working, but, there is not thought to be a link with factors like lifestyle, race and diet. In a small number of cases (about 5%), there is a family history of either motor neuron disease or a related condition known as frontotemporal dementia. However, there is no single test to diagnose MND and diagnosis is solely based on the opinion of a neurologist, on the basis of the symptoms observed and a physical examination. In some cases a specialised test is needed to rule out other possible conditions.
Symptoms of motor neurone disease begin gradually over a period of weeks and months, generally only on one side of the body at the beginning, and gradually get worse with time. Symptoms normally include having clumsy fingers or weaker grip (early signs of weakness). Other symptoms include: wasting of muscles, muscle cramps, hardships with swallowing and communication, excess saliva (difficulties swallowing saliva), and coughing after swallowing. After sometime, a person with motor neuron disease may find themselves unable to move. In a small number of cases (10-15%), motor neuron disease is associated with a type of dementia called frontotemporal dementia that can affect behaviour and personality.
The main types of motor neuron disease are: amyotrophic lateral sclerosis (ALS) (accounts for 60-70% of all cases), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) (http://www.patient.co.uk/health/Motor-Neurone-Disease).
Spinal muscular atrophy (SMA) is an autosomal (a chromosome that is not allosome) recessive genetic disease that causes muscle weakness and progressive loss of movement (http://www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/). Around 1 out of every 40 people are genetic carriers of the disease (they carry the mutated gene but do not actually have SMA) (http://www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/). Gene mutation is a permanent alteration in the DNA sequence that makes up a gene (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/genemutation). Gene mutation occurs in two different ways: they are either inherited from parents (known as hereditary mutation) or they are acquired at some time during a person’s life (known as acquired mutation). Hereditary mutations happen when mutations are present in both the egg and sperm cells. A person that has inherited this type of mutation has it present in virtually every cell in their body, throughout their lifetime. Acquired mutations occur in individual cells at some time during a person’s lifetime. These changes can occur due to environmental factors like ultraviolet (UV) light from the sun, chemicals, and radiation, or if a mistake is made whilst DNA copies itself during cell division (mitosis and meiosis). Acquired mutations are only inherited if they occur in sex cells. According to the National Genome Institute, almost all diseases have some kind of genetic factor. These disorders can be cause by multiple gene mutations, a mutation in a single gene, combined gene mutation and environmental factors, or by chromosome damage or mutation. Gene mutation has been identified as the cause of numerous disorders including spinal muscular atrophy (SMA), haemophilia, Tay-Sachs, sickle cell, anaemia, cystic fibrosis and some cancers (http://biology.about.com/od/basicgenetics/ss/gene-mutation.htm).
The term SMA is used mainly for the most common form spinal muscular atrophy, which is caused by a genetic problem where one copy of the genetic error (mutation in autosomes) is inherited from each parent. SMA is classified into four different categories, from Type I – IV. The classification of SMA depends on the age at which symptoms of the disease arise and the severity of the symptoms. Symptoms of SMA normally include problems with breathing, eating, moving and swallowing; floppy arms and legs (In children with either Type I or II SMA); twitching of the muscles in the arms, legs or tongue. Type I SMA is the most severe, it develops in babies under six months old. Type II is less severe that Type I SMA, it affects babies between the ages 6 to 18 months. Type III and Type IV are the mildest types of SMA. Type III normally affects children around 3 years old. Type IV affects adults. In the most severe cases of SMA (Types I and II), fatal respiratory problems usually develop during childhood. In mild cases such as Types III and IV SMA, life expectancy is normally unaffected (http://www.nhs.uk/conditions/Spinal-muscular-atrophy/Pages/Introduction.aspx).
Spinal muscular atrophy is caused by the deletion of the survival motor neuron gene 1 (SMN1) (http://www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/). In healthy people SMN1 produces a protein known as the survival motor neuron (SMN) protein. In a person with mutated genes, the supply of this protein is absent or is significantly decreased. This results in the deterioration of the nerve cells (motor neurons) connecting the brain and spinal cord to the body’s muscles, therefore causing muscle weakness and gradual loss of movement, because the SMN protein is critical to the survival and health of motor neurons. Spinal muscular atrophy affects 1 in 6000 to 1 in 10000 people.
Myasthenia gravis is a unique long-term autoimmune condition which affects the nerves and muscles, resulting in the muscles becoming weak. An autoimmune condition is caused by the immune system mistakenly attacking and destroying healthy body tissue. Ordinarily, the immune systems white blood cells protect the body from harmful substances, known as antigens. For examples: viruses, bacteria, toxins, etc. antibodies are produced as a counter measure by the immune system that destroy the antigens. In people with autoimmune disorder, the immune system has difficulty distinguishing between antigens and healthy body tissue. Due to this an immune system response that kills healthy body tissue is produced. The cause of the immune system no longer being able to distinguish between antigens and healthy body tissue is unknown at present. A theory suggests that drugs or microorganisms (like bacteria or viruses) may trigger some of these changes. In myasthenia gravis, the immune system accidentally produces antibodies (proteins) that damage or block muscle receptor cells. This stops muscles contracting because the antibodies prevent messages being past from the nerve endings to the muscles. However, it is not understood why the immune system of some people produce antibodies that attack the muscle receptor cells.
Symptoms of myasthenia gravis generally include impaired eye movement and weakness of muscles that are voluntarily controlled, therefore affecting functions such as facial expressions, eye and eye lid movement, chewing, talking and swallowing, and weakness of neck and limbs. However since weakness is a common symptom in many different diseases and conditions, diagnosis of myasthenia gravis is normally delayed or missed. Myasthenia gravis is diagnosed through Blood tests, Genetic tests and Electromyogram. In the U.S about 20 in 100,000 people are diagnosed with myasthenia gravis.
Presently there is no known cure for MND, SMA, OR MG, however there are treatments that can be initiated with aims to ease symptoms to help the person feel more comfortable and have a better quality of life, and compensate for the gradual loss of bodily functions like mobility, communication, breathing and swallowing. For example, for MND, muscle relaxants can help reduce muscle stiffness; medicines such as phenytoin can treat muscle cramps; a breathing mask can help reduce shortness of breath. Right now, the only available treatment for MND that affects the progression of the disease is Riluzole, however it doesn’t stop the progression of motor neuron disease, but only slows it down by a few months (http://www.nhs.uk/conditions/Motor-neurone-disease/Pages/Introduction.aspx). With SMA, depending on the severity, treatment could involve: exercise, to prevent joint stiffness and improve range of movement and flexibility; assistive equipment such as motorised wheelchairs and walking frames if someone with SMA has difficulty moving; nutrition advice and feeding tubes; bracing and surgery to treat scoliosis (curvature of the spine) (http://www.nhs.uk/Conditions/Spinal-muscular-atrophy/Pages/Treatment.aspx). For patients with MG, medication such as pyridostigmine and neostigmine (less common), can prevent the breakdown of acetylcholine, an important chemical that assists the muscles in contracting (http://www.nhs.uk/Conditions/Myasthenia-gravis/Pages/Treatment.aspx). If pyridostigmine is ineffective, steroid tablets can be used to lessen the symptoms. Doctors also often prescribe azathioprine, methotrexate or mycophenolate, to suppress the immune system. Muscle strength can be improved by controlling the production of abnormal antibodies through the use immunosuppressants. In some cases of MG, surgery to remove the thymus gland (a thymectomy) may be recommended. The thymus gland is part of the immune system and is found underneath the breast bone, it is sometimes abnormal in people with MG. In numerous cases, treatment of MG substantially improves muscle weakness allowing a person with the condition to lead a comparatively normal life. Some people may experience permanent or temporally periods where symptoms stop and treatment is no longer needed. Permanent remissions occur in about a third of the people who have a thymectomy (http://www.nhs.uk/Conditions/Myasthenia-gravis/Pages/Treatment.aspx).
Currently, the hope of many is that stem cells of extraneural or neural origin might be modified in vitro (i.e. transforming skin cells into induced pluripotent stem cell (iPS)) (http://www.eurostemcell.org/factsheet/motor-neurone-disease-how-could-stem-cells-help) to differentiate into motor neurons that would migrate to sites of motor neuron loss and restore the motor pathways lost in MND by forming functional connections (Boulis, 2011). The most promising cells so far that can be used for stem treatment of MND are spinal cord stem cells, which are able to produce both motor neurons and a cell call glia. Many of the proteins known as growth factors that contribute to motor neurons development are secreted by glia. There is also a possibility that non-neuronal cells such as glia can be used to prevent further damage to motor neurons and encourage repair through the production of the working version of the protein SOD1, which in some types of MND doesn’t function properly (http://www.eurostemcell.org/factsheet/motor-neurone-disease-how-could-stem-cells-help). Stem cell therapy also has to the potential to be used as a possible cure for SMA, MG and other neurological conditions.
Gene therapy uses genes to prevent or treat a disease by introducing genetic material in cells to compensate for abnormal genes or to make a beneficial protein (MacKenzie, 2010). Gene therapy was found to be well suited as a future treatment for SMA by the Kaspar group: who described a self-complementary (sc) AAV9 vector that crosses the blood-brain barriers after systemic administration; because of scAAV9’s remarkable efficiency in central nervous system (CNS) gene transfer, after intravenous delivery in mice and other larger animals. Using this as a base, the Kaspar group along with Arthur burgees, detail the most successful rescue reported yet in a mouse model of severe SMA. This was achieved by injecting scAAV9 that is carrying SMN1, into the facial vein of mice pups on their day of birth (MacKenzie, 2010). The approach of injecting scAAV9 into mice pups, resulted in the transduction of 40% of motor neurons, and an extension of the lifespan of the mice from 2 weeks to more than 250 days, combined with almost normalised neuromuscular electrophysiology and normal motor function (MacKenzie, 2010).
This preliminary data obtained in the gene therapy rescue of SMA in the mouse model, reported by the Kaspar group and Arthur Burghes (a pioneer of SMA), suggests that the same approach could be used in primates. The authors investigated systemic injection of scAAV9-GFP in a cynomolgus monkey (1 day of age). After four weeks, the magnitude of GFP in spinal motor neurons recorded was similar to that shown by the mice (MacKenzie, 2010), boding well for possible application to humans. This news, along with recent encouraging reports of AAV gene therapy of retinal disease, supports the further rehabilitation of gene therapy as a credible therapeutic alternative for neurological diseases, including MG, SMA and MND.
The stage seems set: with seemingly untreatable disorders of unknown pathogenesis; an unknown presymptomatic way of diagnosis; and, the small possibility of a cure through gene therapy and stem cell therapy, which are by far the best hopes, not only for MND, SMA and MG, but also for other neurological diseases. However, gene therapy and stem cell therapy are subject to a lot of public disagreement. For gene therapy this is due to fact that, gene therapy targeted at germ cells (egg and sperm cells), (known as germline gene therapy) could be pass on to next generations. Whilst it spares a family and their future generations from a specific genetic disorder, there’s a possibility it could affect the development of a fetus in unexpected ways or have yet unknown long-term side effects (http://ghr.nlm.nih.gov/handbook/therapy/ethics). Because the people who are going to be affected are not yet born, they are unable to choose whether to have the treatment, resulting in big debates one whether germline gene therapy should be used. Other ethical concerns involve negative impacts on what society thinks is “normal”, and discrimination toward those with the “undesirable traits” that arise from using gene therapy as a form “modification” for unwanted traits or to make “genetic improvements”. The idea of stem cell therapy is also controversial. Whilst it can used for the treatment of many diseases including neurological ones, there are ethical problems involving how it is obtained. For example, stem cells obtained from the embryo, because the embryo is viewed as a potential person. Due to this, taking stem cells from an embryo is considered to be murder, however, it’s argued that, an early embryo that hasn’t be implanted into the uterus doesn’t have properties we associate with being a person, and therefore can and should be used for the benefit of patients (who are persons).
Nicholas M. Boulis. (2011). Gene Therapy for Motor Neuron Disease.Gene Vector Design and Application to Treat Nervous System Disorders. 33 (3), p41-49
Alex MacKenzie. (2010). A severe inherited neuromuscular disease is corrected in mice by intravenous gene delivery.Gene therapy for spinal muscular atrophy. 28 (3), 235-237