Researchers from Stanford University’s School of Medicine in the United States have announced that they have successfully treated stroke survivors who were paralyzed by the disease, aiding them to walk once again.
According to the researchers, the survivors used in the trial needed a wheelchair for the rest of their lives, as they were medically considered to be paralyzed forever. The trial has been published in the journal Stroke.
With the permission of the survivors, the researchers have achieved what has never been done before in neurosurgery. Stroke, sometimes called brain attack, occurs when the blood supply to part of the brain is blocked, or when a blood vessel in the brain bursts. In either case, parts of the brain become damaged, or die. According to the American Centers for Disease Control and Prevention, stroke kills almost 130,000 people a year in the United States. Stroke is also a leading cause of serious long term disability in the country.
The researchers explained that 18 stroke survivors agreed to allow doctors to drill a hole in their skull and inject stem cells into the damaged part of their brain. It is said the survivors’ strokes had occurred between six months and three years, previously. Researchers have theorized in the past, that brain will no longer regenerate after six months of death. They also said stem cells could not integrate into the brain to become neurons.
But the theory was proved wrong with the new therapy attempt by the Stanford researchers. The trial showed that stem cells secrete powerful chemicals for growth and regeneration, which the brain can use to restore its function.
The therapy is said to have completely turned the adult brain back to an infant brain, rebuilding it, and helping them to walk again. The patients are said to have an average age of 61.
The researchers concluded that the new therapy could also work for other neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s and Lou Gehrig’s disease.
All the patients involved with this groundbreaking trial had suffered what is known as ischemic strokes, where a clot prevents blood getting to the brain. This defect leads to brain cell death. According to the procedure used, the researchers drilled a small hole in the skull above the damaged area so that SB623 stem cells could be injected at several spots around the edge of the injury. The stem cells used in the trial were taken from the bone marrow of two donors.
After the process was completed, the patients were reportedly sent home the following day. It is said some complained of initial headaches, because of the surgical procedure, but after the headache was treated, there were no long-term side effects.
They were monitored with blood tests, clinical evaluations and brain imaging. The researchers said they noticed that the implanted stem cells do not survive very long in the brain, but recovery continued, even after they had vanished. Overall, the researchers revealed that there was 11.4 point improvement on the Fugl-Meyer test, which gauges how well stoke patients can move. The injection was done two years ago, and there has since been no problem with the then patients.
Chair of Neurosurgery at Stanford, Professor Gary Steinberg, who led the trial, was quoted as saying by the Telegraph: “The remarkable recovery we saw in many of these chronic stroke patients was quite surprising. This wasn’t just ‘they couldn’t move their thumb and now they can’. Patients who were in wheelchairs are walking now. Their ability to move around has recovered visibly. That’s unprecedented. The study changes our prior notion that patients can’t recover much more after the first six months following a stroke because the circuits are dead, or irreversibly damaged. In a simple sense, the stem cell transplant turns the adult brain in a neonatal of infant brain which recovers well after a stroke or other injury.” Professor Steinberg is said to have spent 15 years researching stem cells.
The Research Communications Manager at the Stroke Association in the United Kingdom, Dr Shamim Qadir commended the researchers for their initiative, hoping that the second phase of the trial will also be successful.
“There is an urgent need for alternative treatments. This trial adds to a growing body of early clinical evidence suggesting stem cell treatment could promote recover in people months, and even years after having a stroke. This is positive development and brings much needed hope for the many people living with disability. We look forward to the results of the Phase II trial which could tell us much more about this type of stem cell treatment,’ Dr Qadir said.
UNDERSTANDING STEM CELLS
Broadly speaking, stem cells are used to treat disease or repair damaged tissue, to understand disease processes and for drug discovery. They are able to be used for these purposes because they belong to a special group of cells that are capable of differentiation. This means that they can form any of the more than 200 different cell types found in our bodies.
Different kinds of stem cells
Pluripotent stem cells are those that have the ability to form all the cells and tissues in the body (excluding the placenta). They are classified into either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs).
While ESCs are derived from the early embryo, induced pluripotent stem cells are created when adult stem cells are reprogrammed to become like ESCs. By culturing adult cells in the laboratory in the presence of genes which are functional in the early embryo, the adult genes are switched off and the cells’ embryonic genes switched on.
As our bodies develop, cells become more restricted in their capacity to differentiate into other cells types, and are termed multipotent or unipotent. After we are born, adult stem cells replace cells lost through normal wear-and-tear or disease.
Adult stem cells are found throughout our bodies. There are several types. For example, hematopoietic (blood) stem cells are found in the bone marrow. They give rise to red blood cells, white blood cells and platelets. Another example are neural stem cells found in the nervous system. Mesenchymal stem cells are found in fat (adipose) tissue, bone marrow and the umbilical cord.
What can stem cells be used for?
Adult stem cells have been used for more than five decades to treat certain blood cancers and genetic or immunological disorders. Known as bone marrow or hematopoietic stem cell transplantation, this procedure replaces the normal stem cells in a patient’s body that have been destroyed by high dose chemotherapy.
Stem cells are also used to replace skin in major burn injuries and to heal chronic wounds. A wide-range of other potential uses are being tested but at this stage are considered to be experimental. These include treatment for heart disease, cerebral palsy, Alzheimer’s and Parkinson’s diseases, diabetes and spinal cord injury.
Adult stem cells are collected on a routine basis in many parts of the world. Current sources include the bone marrow, circulating blood, and cells harvested from umbilical cord blood. Adult stem cells, and in particular those derived from umbilical cord blood, can be stored for future use either in a public or a private cord blood bank.
Pluripotent stem cells are not yet used to treat patients routinely but are being tested in clinical trials for a number of diseases including blindness. At present they are mainly used to understand disease processes and for drug discovery.
Why are stem cells controversial?
More than 90% of the work involving stem cells is not controversial. This includes the therapies that are legitimately administered every day as well as most of the research work being done in many parts of the world.
Nonetheless, there are a few areas in the stem cell field that have become controversial. These include:
- embryonic stem cells, whose preparation is seen to result in the destruction of a potential life. This is because ESCs are derived from a small group of cells in a five day embryo (called the inner cell mass) that under normal circumstances would go on to form an entire living organism;
- reproductive cloning in which a clone or copy of an organism is produced from a single cell removed from that organism; this is the process that produced Dolly the sheep. Reproductive cloning is universally banned in humans; and
- stem cell tourism, where patients pay large amounts for unproven stem cells therapies, contravening ethical norms and safety standards.
STEM CELLS IN THE INTERNATIONAL COMMUNITY
Exploration into the use of stem cells has created a cauldron where scientists and regulators are increasingly pressurised to find ways of fast-tracking promising research into novel therapies.
Many countries are developing guidelines and legislation to balance the provision of stem cell therapies as quickly as possible, while still ensuring the safety and efficacy of treatments.
At the centre of this is the accelerated, or conditional, approval of medicine still under clinical development. This is opposed to medicine already proven to be safe and effective in humans, formally approved by the relevant regulatory authority and legally available for sale to the public.
Although the South African legal systems do not provide for any accelerated or conditional approval, heed should be taken of global developments. This will ensure that legal systems allow local scientific innovation to keep up with global pace setters and that patients are protected.
Stem cells and investigational medicine
The use of investigational medicine, as we know it today, came about in the late 1980s. In an attempt to address lengthy drug development cycles and a growing AIDS epidemic, the US was forced to reconsider its strict guidelines around investigational medicine. It eventually amended them to allow access to investigational medicine under certain conditions.
This developed into the Food and Drug Administration’s (FDA) system of expanded access. This allows patients with serious conditions to receive investigational medicine that has not yet undergone formal product approval.
There are three prescribed categories of people who can get expanded access to investigational medicine:
- intermediate-size patient populations; and
- widespread use under a treatment protocol.
For individual patients, the decision lies with a physician. They need to confirm that the medicine does not pose a greater risk to the patient’s health than the disease itself.
When large numbers of patients are involved, the FDA must still find evidence that it is safe to use. To qualify, the FDA must determine whether the condition is serious or immediately life-threatening, and that there are no alternative satisfactory treatments available. Access to investigational medicine must also not interfere with the necessary clinical trials required to receive formal product approval.
Similar to all other therapeutics that qualify as biological medicine, stem cells must go through lengthy clinical trials to prove their safety and efficacy before they can be approved by the relevant regulatory authority for public use. Before they received the final approval, stem cells remain investigational medicine.
This should not be confused with the countless bogus stem cell treatments often advertised online. Many of these treatments have not:
- undergone clinical trials;
- passed the first phase of these trials; or
- received the go-ahead from authorities to be used as an investigational medicine.
Expanded access is gaining momentum
In many countries, access to stem cell treatments still classified as investigational medicine, is gaining momentum.
In addition to the US’s expanded access guidelines, the Right to Try Act was introduced in July this year. If passed, the bill, which is complementary to similar state laws, will stop the federal government from taking action to stop expanded access of investigational drugs to terminally ill patients. This will severely limit the FDA’s regulatory authority over expanded access in these instances.
Although federal laws trump state laws, twelve states have already enacted so-called “right-to try” legislation. This has created enormous legal ambiguity as these state laws are not really enforceable. But, in practice, the fear of violating the FDA’s requirements causes a reluctance to actually use these state laws.
Similarly, the European Medicines Agency has started a public consultation process of revised guidelines to implement accelerated access and conditional marketing authorisation. These are based on less complete clinical data. This will also accelerate patients’ access to medicines and address unmet medical needs.
The guidelines are specifically aimed at innovative medicines and target diseases where no treatment is available. It could provide patients with a major therapeutic advantage over existing treatments.
This public consultation process is hot on the heels of the highly debated Stamina Foundation debacle. This involved an Italian court ruling that unproven stem cell therapy on a three-year-old child with Krabbe disease, an incurable neurological condition, could continue.
The decision was based on the compassionate use of the therapy in patients with severe incurable diseases as a last resort. It also followed an official endorsement by the Italian Government in March 2013. The government decreed that the Stamina Foundation were allowed to continue stem cell therapy on 32 terminally ill patients. Their permission came without proof that the cell-based therapies were manufactured according to Italy’s legal safety standards.
In Japan, the revised Pharmaceutical, Medical Devices and other Therapeutic Products Act came into effect in November 2013. It contains a specific section for regenerative medical products and allows for conditional, time-limited marketing authorisation to be given. The authorisation will only happen if a product’s safety is ensured.
The available clinical trial results should also predict likely efficacy. But the authorised products will still be subject to further safety and efficacy tests between conditional and final approval.
Covering South Africa’s landscape
Stem cell therapy holds the possibility of curing a large number of diseases. However, almost all of these therapies are still in early development and clinical trial stages.
Access to these therapies prior to regulatory approval might not only relieve human suffering, but will also legally enable scientists to test and prove their efficacy via an alternative means (other than in the clinical trial setting).
Although the benefits from the developer’s perspective are apparent, the patient’s safety and best interest must remain top-of-mind. Most importantly, the expectations of potentially vulnerable patients should be managed sensitively and accordingly.
The universal nature of stem cells therapy begs for harmonised international regulation, and South Africa can learn and benefit from current global developments.
STEM CELLS CAN BE MADE FROM HUMAN SKIN THROUGH REPROGRAMMING
Scientists have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body.
While researchers have previously been able to make embryonic stem cells in monkeys and mice, this is the first it has been done with human cells.
The results are published today in the journal Cell.
The research team, from the Oregon Health & Science University and the Oregon National Primate Research Center, used a process called somatic cell nuclear transfer (SCNT), otherwise known as therapeutic cloning.
This involves transplanting the nucleus of one cell, containing an individual’s DNA, into an egg cell that has had its genetic material removed.
The unfertilised egg cell then develops and eventually produces stem cells, which could one day be used to replace cells damaged by injury or illnesses such as Parkinson’s disease, multiple sclerosis and heart disease.
“A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells,” said lead researcher Dr Shoukhrat Mitalipov.
“While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine,” he said.
The research does not involve the use of fertilised embryos, which has been the topic of significant ethical debate since Dolly the sheep was cloned in 1996.
“Our research is directed toward generating stem cells for use in future treatments to combat disease,“ Dr Mitalipov said.
“While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning.”
Associate Professor Andrew Laslett, Research Group Leader, Stem Cells at CSIRO Materials Science & Engineering, said the findings were “big news” for the stem cell research community and the general public.
“Many groups worldwide, including some in Australia, have been attempting this for a long time,” Professor Laslett said, adding that the breakthrough provides an alternative to induced pluripotent stem (iPS) cells, which can lead to unwanted gene mutations.
“Previous non-human studies have shown that SCNT embryonic stem cells are closer to ‘normal’ embryonic stem cells than are iPS cells,” he said.
“Hence, SCNT embryonic stem cells may be a better option than iPS cells for some applications.”
Professor Bernie Tuch, Director of the NSW Stem Cell Network, said the only downside was the technique required availability of good quality human eggs, because “paid egg donation for this purpose is currently not allowed in Australia”.
Professor Tuch is a member of the Research Consortium at Fertility East, which is attempting to produce stem cells from human eggs that are donated without payments. The program is approved by the NHMRC Embryo Licensing Committee.
But Professor Ed Stanley from the Murdoch Childrens Research Institute’s Stem Cell Technology Laboratory disagreed that the paper would have any bearing on the therapeutic use of stem cells.
“Essentially, the paper shows that human eggs can be used to reprogram tissue-derived cells (for example, skin cells or blood cells) so they become like embryonic stem cells. However, people can already do this using other methods that are much more accessible and simpler,” Professor Stanley said.