Spina Bifida

Spina bifida is a congenital birth defect that occurs due to “splitting” of the spinal cord due to failure of proper closure of the neural tube – the embryologic origin of the nervous system. Spina bifida is one form of Neural Tube Defects (NTDs) and it has three ascending degrees of severity according to how much of the spinal cord is left exposed; namely spina bifida occulta, meningocele, and myelomeningocele. Spina bifida can often be diagnosed antenatally – during pregnancy – though treatment options are still limited especially for more severe forms and surgery being the main, and perhaps only, form of treatment (1).

Symptoms of spina bifida depend on the severity/type as well as the spinal cord level it occurs in; where the higher the defect the worse the symptoms. However, most cases occur low within the spinal cord with most neurological symptoms affecting the lower limbs and bladder and bowel functions – though higher lesions are still possible (1).

Children with spina bifida often have impaired movement and sensation below the level of the NTD – causing weakness or paralysis. They might also have urinary (bladder) and/or fecal (bowel) incontinence. Although spina bifida does not affect the brain by itself, it is often associated with other neurological diseases that might affect brain and cognitive development – such as Chiari malformation and hydrocephalus. Such associated disorders might affect normal brain development of children with NTDs, and therefore affect their intelligence, behavior, speech, social development…etc. (1, 2).

90% of spina bifida cases are discovered during an ultrasound before 18 weeks of pregnancy. Diagnosis is commonly done through a blood screening to test for alpha-fetoprotein (AFP) in the mother’s blood. Babies create this AFP protein that commonly reaches the mother’s bloodstream, but if the level of AFP is too high it could be a sign of spina bifida.

To determine the reason for high levels of AFP, a doctor will have an ultrasound done to confirm the reason. If further testing is needed, a doctor can perform an amniocentesis test in which a part of the amniotic fluid surrounding the baby is tested. If that fluid has a high concentration of AFP as well, it could be because the skin that should cover the spinal cord is not there and is causing a leakage of the baby’s spinal fluid.

MRI and CT scans are also possible tools for post-natal diagnosis.

Given that NTDs occur due to congenital nerve degeneration, its treatment options are limited similar to lots of other neurological disorders. Current treatment options for spina bifida include (1, 3):

• Surgery: Currently, early surgery (within 48 hours of birth) is the main treatment option, and even then its only aim is to close the anatomical skin defect present due to spina bifida, in order to prevent the risk of infection (ex. meningitis). However, surgery doesn’t correct the actual neurological deficit present since it has already occurred during pregnancy.

• Fetal Surgical Intervention: Some trials have tested the benefits of intervening and correcting spina bifida during pregnancy – before permanent neurological damage. These trials reported clinical benefits, yet the long-term efficacy and safety of such techniques still need to be studied further before becoming the standard of care due to the high risk of complications to both the mother and the fetus.

• Supportive Treatments: These include treatments aiming to improve the quality of life of people with spina bifida. Some examples include physiotherapy, nutritional therapy, medications to improve bladder and bowel function, social therapy, and surgical correction of associated bone deformities.

To date, there has not been a single study – to our knowledge – that has compared different types of stem cells, concerning safety and efficacy, particularly in patients with NTDs. However, we can summarize different stem cell sources that have been tested in these disorders. Each form of stem cells has its own benefits and drawbacks as will be mentioned. Different stem cell sources that have been tested in different neurological disorders include (3, 6, 10):

• Mesenchymal Stem Cells: These are stem cells obtained from adipose tissues, bone marrow, or umbilical cord tissues – which we actually use at Beike. These cells can be easily produced in larger numbers to accommodate higher number of patients and allow better efficacy, have better response in neurological diseases – including spina bifida – have better differentiation capacity into neurons, and have better anti-cell death effect in case of degenerative conditions like NTDs that affect neurological development– compared to other stem cells. Mesenchymal stem cells can be obtained from different sources including the umbilical cord, bone marrow, and adipose tissue.

• Embryonic Stem Cells: Another type of stem cells includes embryonic stem cells. These cells can also differentiate into photoreceptors; yet they are difficult to obtain and have ethical concerns regarding their sources.

• Adult Pluripotent Stem Cells: These are another source that can be produced in large numbers; yet their differentiation abilities are once again limited.

• Neural Stem Cells: These are another type that has particular benefits in neurological diseases through the production of neurotrophic factors; though their differentiation is also limited

After carefully reviewing all of the benefits and risks of each type, we have decided to use mesenchymal umbilical cord-based stem cells as our main source since they have been the most extensively studied type in neurological conditions, including NTDs, with the least reported side effects (5, 6, 8). This is in addition to also using umbilical cord blood cells (hematopoietic cells) concurrently to provide additional benefits from using two types of stem cells; with each contributing to neuro-regeneration through different complementary mechanisms.

In addition to the source of stem cells, there are also multiple routes of stem cell administration. Most clinical trials testing stem cell therapy in spina bifida use either one of two routes; which are (8, 9):

• Intravenous (Into the blood)

• Intrathecal (Into the CSF surrounding the brain through lumbar puncture)

At Beike, we use combined intravenous and intrathecal routes concomitantly to achieve the best results with the least possible side effects.

At Beike, we use umbilical cord stem cells for spina bifida, both umbilical cord-related mesenchymal/tissue and blood/hematopoietic cell samples donated from healthy mothers after normal birth. As previously mentioned, this concomitant administration of both types of stem cells, mesenchymal and hematopoietic stem cells, provides better results.

There is no specific timing for stem cell treatment; but like many other neurological conditions and based on the trials testing stem cell therapy on infants of different ages (8, 9), we generally recommend seeking stem cell therapy early after diagnosis – i.e. during infancy. This is because the earlier the stem cell intervention, the easier it is to prevent further damage of the neurons and to be able to restore normal brain and spinal cord functioning before permanent damage takes place. We still need to report that clinical benefit is not 100% guaranteed as is the case with any intervention, and consulting our specialists prior to undergoing the procedure is of utmost importance in order to gain more insight on the procedure and the estimated possibility of treatment success for your individual case.

Of course, no treatment is without complications, and stem cell therapy is the same. However, despite its novelty, stem cell therapy has limited side effects, if used properly, with comparable general side effects to those experienced with regular blood transfusion or foreign organ transplantation (ex. allergic reactions, cell rejection, or fever). Additionally, in studies specifically studying stem cell therapy in patients with spina bifida, no significant side effects were reported and none were life-threatening or had life-long consequences (8, 9). They were also easily managed medically at the time of their occurrence.

Factors that might affect your response to stem cell therapy for Spina Bifida include:-

• Dose/Number of stem cells: The higher the dose of stem cells – within limits of course – the better the response. At Beike Technology, we administer an optimum dose of around 120-400 Million Cells (depending on the person’s weight and age) for people with NTDs.

• Route/Method of administration: Studies have shown that combining intrathecal injection (through lumbar puncture directly within the brain’s CSF) with the traditional intravenous route provides better response than administering intravenous injections alone (which causes stem cells to go to other organs than the brain before reaching the brain). Therefore, at Beike Technology, we use both intravenous and intrathecal routes concomitantly in order to obtain the maximal efficacy; while ensuring the least possible side effects or toxicity.

• Type of Stem Cells used: Mesenchymal stem cells have the best-proven efficacy in spina bifida – compared to other types of stem cells – which is why we use umbilical cord tissue mesenchymal cells at Beike as the main source of stem cells. Also, believing that each type of stem cells has its own primary benefit, we have decided to additionally extract and use umbilical cord blood stem cells (hematopoietic stem cells) concomitantly to achieve better results in patients with spina bifida.

• Timing of stem cell transplantation: Early intervention is crucial for people with NTDs – prior to reaching the end of the time window needed for adequate brain development. Therefore, we recommend early intervention soon after birth and diagnosis.

• Follow-up Time: Significant benefits from stem cell therapy in patients with NTDs begin appearing around 3 to 6 months after stem cell therapy, and most people reach their full potential around 6 to 12 months after treatment. At Beike Technology, even after discharge, we provide you with a full follow-up program beginning as early as one month and up to one year after transplantation. You have complete access to our professional team even after you leave our center.