Overview

The motor neurone diseases (or motor neuron diseases) (MND) are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. Forms of motor neuron disease include: a) amyotrophic lateral sclerosis (ALS) (sometimes called Lou Gehrig’s disease) b) primary lateral sclerosis (PLS) c) progressive muscular atrophy (PMA) d) bulbar e) pseudobulbar palsy – spastic f) progressive bulbar palsy – spastic and flaccid. Spinal muscular atrophy (SMA) is classified under MND by MeSH, but not by ICD-10. Signs and symptoms: Symptoms usually present themselves between the ages of 50-70, and include progressive weakness, muscle wasting, and muscle fasciculations, spasticity or stiffness in the arms and legs, and overactive tendon reflexes.

Patients may present with symptoms as diverse as a dragging foot, unilateral muscle wasting in the hands, or slurred speech. Neurological examination presents specific signs associated with upper and lower motor neuron degeneration. Signs of upper motor neurone damage include spasticity, brisk reflexes and the Babinski sign. Signs of lower motor neurone damage include weakness and muscle atrophy. Note that every muscle group in the body requires both upper and lower motor neurons to function. The signs described above can occur in any muscle group, including the arms, legs, torso, and bulbar region.

The symptoms described above may resemble a number of other rare diseases, known as “MND Mimic Disorders”. These include, but are not limited to, multifocal motor neuropathy, Kennedy’s disease, hereditary spastic paraplegia, spinal muscular atrophy and monomelic amyotrophy. A small subset of familial MND cases occur in children, such as “juvenile ALS”, Madras syndrome, and individuals who have inherited the ALS2 gene. However, these are not typically referred to as MND, but by their specific names.

Diagnosis: The diagnosis of MND is a clinical one, established by a neurologist on the basis of history and neurological examination. There is no diagnostic test for MND. Investigations such as blood tests, electromyography (EMG), magnetic resonance imaging (MRI), and sometimes genetic testing are useful to rule out other disorders that may mimic MND. However, the diagnosis of MND remains a clinical one. Having excluded other diseases, a relatively rapid progression of symptoms is a strong diagnostic factor.

Although an individual’s progression may sometimes “plateau”, it will not improve. A set of diagnostic criteria called the El Escorial criteria have been defined by the World Federation of Neurologists for use in research, particularly as inclusion/exclusion criteria for clinical trials. Owing to a lack of clinical diagnostic criteria, some neurologists use the El Escorial criteria during the diagnostic process. The “bulbar region” refers to the mouth, face, and throat. It is possible that Transcranial magnetic stimulation can be used to diagnose MND.

Conventional Treatment

1. Oral taking of Vitamins E and B.
2. Intramuscular injection of ATP (100 mg/day), coenzyme A (Co A) and citicoline (250 mg/day).
3. Oral taking of diazepam (2.5–100 mg/day).
4. Trying some drugs such as TRH, interferon, venene or testosterone.
5. Massage or passively moving.
6. Nasal feed for patient with dysphagia to take nutrition and water.
7. Using respirator to help patient with respiratory muscle paralysis.
8. To prevent lung infection.
9. Using traditional Chinese medicine.

Limitations of Conventional Treatment

Currently there is no cure for ALS. The only drug that affects the course of the disease is riluzole. The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months. The lack of effective medications to slow the progression of amyotrophic lateral sclerosis (ALS) does not mean that patients with ALS cannot be medically cared for. Instead, treatment of patients with ALS focuses on the relief of symptoms associated with the disease. This involves a variety of health professionals including neurologists, speech-language pathologists, physical therapists, occupational therapists, dieticians, respiratory therapists, social workers, palliative care specialists, specialist nurses and psychologists.

Stem Cell Treatment

The effects of current medication are not satisfied due to relative short course and high fatality rate of motor neuron disease. However, stem cell and gene therapy have become major means for treatment of motor neuron disease as the rapid development in biotechnology. In theory, stem cells can differentiate into neurons to replace the locally damaged neurons, and generate various neurotrophic factors to protect neurons. The neural stem cell transplantation can improve conditions of the patients to stop disease development so as to prolong patient’s life and improve the life quality. The muscle strength of the right part of the body of some patients can be improved in 3 days after the transplantation. Some patients can turn over freely and stand up in one week after the treatment. Moreover, some patients are able to hold a bowl with the right hand.

Indications of Stem Cell Treatment

Scientists are not sure why motor neurons start to lose function. They believe several inter-related factors cause MND, including: excess glutamate; cell metabolism transport disturbances; unusual protein aggregates in motor neurons; lack of antioxidant production; abnormal mitochondria of motor neurons; inadequate neurotrophic factors; and problems with glia cells that support neurons.

Advantages of Stem Cell Treatment

Stem Cell Therapy Perspectives in Treating Motor Neuron Diseases: The majority of adult stem cells used for the treatment of ALS and SMA are autologous; only one stem-cell-based product is allotransplant. Patients’ own bone marrow was the source of adult stem cells in four products, patients’ own skin in one product, fetal spinal cord tissue in one product, and embryonic stem cells in one product. Motor neurons were differentiated for use in two products. Possible positive therapeutic effects of motor neuron cell-based products for the treatment of both ALS and SMA may be expected. When evaluating results of products in this pipeline, it is important to remember that the alternative for patients is death, and any positive result will have enormous significance.

In a study, NSCs from mice in which a green marker protein was expressed only in nerve cells known as motor neurons (the cells that are defective in SMA) were transplanted into the fluid bathing the spinal cord of mice with an SMA-like disease. The transplanted cells developed into a small number of motor neurons and the treated mice showed improved muscular function and increased lifespan, when compared with untreated mice. Further analysis indicated that the major effect of NSC transplantation was that the transplanted cells improved the survival and function of the motor neurons already in the mice.

Stem Cells, may be pluripotent or multipotent, are important for living organisms for many reasons. Pluripotent stem cells can give rise to any type of cell in the body except those needed to support and develop a fetus in the womb. Stem cells that can give rise only to a small number of different cell types are called multipotent.

Neural Stem Cells (NSCs) are capable of self-renewal and differentiation into neurons. When transplanted into the damaged site of the brain, NSCs are able to differentiate into corresponding neural cells at the focus, and produce various neurotrophic factors. As a result, the damaged cells will be replaced, the nerve loop will be reconstituted and the degeneration of nerves or semi-apoptotic cells will be inhibited.

The advantages of the stem cells transplantation are followed:

• Relatively safe compared with most of the conventional treatments
• No immunological rejection, since stem cells have very low immunity
• Not affected by the blood-brain barrier, because stem cells are directly injected into the damaged tissues.

Advantages of Fetal Stem Cell Treatment

In the World Stem Cell Therapy Center, the stem cells used for most of our therapies are the Fetal Stem Cells (FSCs). FSCs treatment has a number of advantages compared with the transplantation of any other types of stem cells, i.e. adult, cord blood and animal stem cells.

1. Avoid the histocompatibility problems

   Histocompatibility has always been regarded as a stumbling-block of transplantology, causing rejection of transplanted organs, bone marrow and cord blood stem cells, etc., thus requiring additional special methods aimed at suppression of the recipient’s immune system. With fetal stem cell transplantation, it is possible to avoid any side effects related to histocompatibility and ensure engraftment and proliferation of the administered cells, as well as their functioning in the body for many months and even years without immunosuppression.

2. Ensure both target and systemic effects

   In addition to targeted cell effects predicted and described by researchers, fetal stem cell transplantation can exert powerful systemic effects related to psychoemotional sphere, physical activity, immune system, homeostasis and functioning of internal organs, achieved via regulatory systems of the recipient’s body. Each type of stem cells produces certain specific tissues. Human regulatory systems, controlling the transplanted cells, guide the development and specialization of those cells in compliance with body needs, thereby ensuring precise specialization of clinical effects. Only natural tissues are used without any genetic engineering or cloning process for the cell cultures. The effects of the FSCs treatments are significantly different from most other medicinal treatments. Within 1–2 months after transplantation, early clinical effects of FSCs transplantation can be observed. The long-term effects of the FSCs treatments can be 6–8 months and even 2–3 years. In some cases, the engraftment will stay for lifetime.