New breakthrough using neural stem cells combined with Edaravone (Radicut) and Nerve Growth Factor(NGF) in the treatment of ALS/MND.

ALS (Amyotrophic lateral sclerosis)/MND is a kind of irreversible deadly motor neuron disease(MND). The patient's normal motor neurons will decrease continuously once they get ALS/MND and their movement function will reduce quickly. Past research shows ALS/MND patients can only survive 3-5 years. Until now there has been no cure or very effective treatment method. Even Riluzole, which had been approved by FDA as the only effective medicine that can be used, can only prolong the ALS/MND patient's life by around 3 months and  cannot help the patient get any improvement in the body motor function disturbance.

In the past few years doctors in Wu Medical Center started to use cell replacement technology with neural stem cells to treat the ALS/MND patients. The treatment can increase the normal healthy motor neurons level and at the same time they combined it with Edaravone (Radicut) and Nerve Growth Factor (NGF). Edaravone is a kind of free radical scavenger which improves ALS/MND patient's internal body environment. It helps to protect the patient’s autologous motor neurons and can also help the work of the new motor neurons differentiated from the implanted neural stem cells. NGF can also benefit the survival of implanted neural stem cells and effectively improve the function of new motor neurons, and therefore improve patients' motor function.

The clinical control study showed the treatment effect of a combination of neural stem cells and Edaravone (Radicut), NGF was much better than single use of Edaravone or Riluzole. The results were inspiring. Most patient’s movement ability improved and there was no more decline post treatment. The treatment helped patients reverse the progress of the disease and clearly helped to prolong their life and improve life quality. The new treatment method provided ALS/MND patients with a new chance.

By Drs.Li-Ke Wu, Xiaojuan Wang, Bo Cheng, Susan Chu, Xiaoling Ren and Shuangshuang Liu

Wu Medical Center, Bejing, China

About ALS

Amyotrophic lateral sclerosis (ALS) belonging to a group of disorders known as Motor Neuron Diseases (MND). It is characterized by the gradual degeneration and death of motor neurons. ALS is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles (muscle action we are able to control, such as those in the arms, legs, and face). The incidence of ALS 5-8/100,000. Most of the patients developed the symptoms when their age reached over forty. The patient would begin to present weak symptoms and with their age increasing, the incidence increases as well. Some ALS patients may have symptoms of ALS plus dementia or Parkinson.

The most common symptoms seen in ALS patients are when one of the side fingers has an awkward fine motor, stiff fingers and/or mild weakness of hand and muscles atrophy of hand. Then the disease progresses gradually after the first symptom. The patient will then suffer from weakness in the upper limbs and lower limbs, slurred speech, swallowing difficulty and breathing difficulty. The patient could also present signs of Parkinson's disease and other neurodegenerative diseases. Regardless of the occurring pattern and developmental way of the disease, the disease progressed inexorably. More than half of the patients lost the ability of activity in the three years after the onset of the disease. The patients suffered from respiratory failure and the ability to swallow became difficult 90% of the patients lost motor function completely within 6 years. The patients suffered from respiratory failure and circulatory failure and failure of other various organs.


The disease mainly damages the upper and lower motor neurons, anterior horn of the spinal cord, brainstem motor nuclei and the upper and lower part of the neuron in the cerebral cortex. Generally, the large nerve cells were shown to be damaged early on. After the cells disappeared, they were replaced by astrocytes and microglia cells. So, there were often no abnormal changes in the early MRI's.

ALS Treatment

There is no specific treatment plan for any type of motor neuron disease; there is only a type of supportive treatment. Current progress: With the development of biotechnology, using cell technology to control the ALS disease is developing too. WMC found that:

1. Cells have a good therapeutic reaction to such diseases.

2. ALS has specific characteristics, such as nerve demyelination and gliocyte replaced and proliferative. This provides basis for targeting a location.

3. ALS patients are generally seen to have motor neuron loss of lamina propria, which provides anatomy bracket for stem cell. At the same time, this supports both cells homing differentiation.

WMC believes that drug control and physical training play an important role in cell repair for patients will ALS undergoing treatment.

Commentary: ALS/MND gene therapies - progresses and limitations

By Drs. Like Wu, Xiaojuan Wang, Bo Cheng, Susan Chu, Shuangshuang Liuand and Fang Peng 

Wu Medical Center, Beijing, China

Amyotrophic Lateral Sclerosis (ALS) belongs to a group of diseases called Motor Neuron Diseases (MND). It is a disease that attacks the upper motor neurons and lower motor neurons, and it will result to bulbar zone (the muscle controlled by medulla oblongata), four limbs, trunk, chest and abdomen’s muscle weakness and atrophy. The patients will have respiratory failure, cardiac failure or even die in 3-5 years due to whole body muscle atrophy. There is more and more relational disease gene locus not only in the familial ALS patients but also in the sporadic ALS patients. All of these show that ALS/MND is a kind of genetic disease. It is relational to 8 “major genes”, and the 21q22.11ALS1 (SOD1: Cu/Zn superoxide dismutase1) gene is the most popular one. Besides, there are 2q33-34ALS2gene (ALSin), ALS3gene, 9q34 ALS4 gene, 15q12-21 ALS5gene, 18q21 ALS6gene, 17q FTDP (Tau gene) and 9q21-22 FTD gene. All the gene mutations make the patients more vulnerable to remove the intoxicants in body especially the glutamic acid, methoxylradical and toxic protein. The motor nerves are degenerated and the final result will be death. There is still no effective regular medical method to treat it, even the drugs that are approved by FDA. Riluzole is not able to improve the patients’ condition or improve their motor function. It can only prolong 3 months life. That is why it is important to advance a new and effective treatment method.

Gene therapy is an ideal way to treat the ALS/MND, because ALS/MND is a kind of genetic disease. The goal of treatment is to replace the abnormal gene with normal cells. Using this treatment method, there are some terms that should be followed:
1. Determinate single gene disease. 2. Only for somatic cell. 3. The relative and operability of target cell. 4. Better effect and lower or no harmfulness. 5. Stable and unique time expression. 6. Experiment on animals. ALS is not monogenic disease and multisite mutation is a limiting factor. The only commonly used method is still viruses’ method. Scientists and doctors are trying to use this relative high-performance supporter to import the treatment of DNA into the patients’ cells. But is it possible for us to reform all the damaged cells effectively and safely if we found the correct virus? We know that the virus is able to get into the damaged cells and transport the useful gene into them successful, but we also know it results also to many kind of safety problems and many patients were dead. The risks are: 1. Virus leads to infection and injury when it does the self-replication, such as cephalitis or myelitis. 2. The rate of tumors was higher. 3. The expression of target was out of control. All of these explain that it is not a good way to treat ALS/MND with gene-therapy.

Is there a more safe and effective way to repair deficiencies of gene? After more than ten years of research and clinical practice, Dr. Wu and his team used stem cells to treat 126 ALS/MND patients with good effect. More than 85% patients recovered their nerve function. 3 months after the treatment, there were still more than 75% patients maintained the good effects. The stem cells treatment is able to prolong the patients’ life and improve their quality of life. In Wu Medical Center(WMC), Dr. Wu implanted normal stem cells into patients’ body. There were different gene mutations at locus in their bodies. Most of them got improvement. They had not only longer movement time in order to stop the paralysis, but also get relief the disease and improve their life quality. This kind of treatment cannot change the abnormal genes in the patients’ body, but under some drugs control, the injected cells with normal genes, mitochondrion and metabolic functions like neural stem cells (NSCs) can differentiate into motor cells and neuroglia cells or other cells. The neuroglia cells are able to protect the motor cells and repair gene products’ deficiencies to some degree. For example: 1. SOD1 defect, there are over free radical damage, the NSCs are able to differentiate into motor neuron, and that can product SOD1 to remove the radicals in the cells, so that the motor neurons autoxidation would be improved. 2. Excitatory amino acids damaged to motor nerves; ALS patients have acceptor defect of glutamate. The cells cannot transfer the excitatory amino acid. Motor neuron differentiates from neural stem cells (MNDNSC) are able to feel the change of capsule acceptor molecular chaperones and excitatory amino acid’s concentration gradient, so that it can help to remove the glutamate. The motor cells are protected better. So the stem cells treatment is much better than Riluzole, which can only prolong 3 months of life of the patients but not improve the motor function.

WMC considers that at the present stage, the only new and effective treatment method for ALS is replacing/fixing the abnormal cells with normal cells. WMC has found this effective treatment methods and it is very safe. The most important in this treatment is thatit can be repeatedwhen there is no enough cells to stop the disease getting worse.The patients can be injected new and normal stem cells to treat the disease.

Clinical Study of Stem Cells Transplantation for the Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Like Wu , Xiaojuan Wang , Bo Cheng, Susan Chu, Shuangshuang Liu , Fang Peng , Xiang Wang and Shengjie Liu

Wu Medical Center (3-10-2016)

ALS (Amyotrophic Lateral Sclerosis) is also known as MND (Motor Neuron Disease), is a kind of motor neuron degeneration (upper and lower motor neurons) caused by a gene mutation which leads to the gradual diffused muscle weakness and atrophy including the bulbar area (mainly indicates the muscles controlling the respiratory function, swallowing and speech pronunciation), four limbs, trunk, chest and abdomen, and finally leads to respiratory and circulatory failure. ALS is a kind of deadly disease which progresses very quickly, the patient’s body condition will decline at a fast rate, and because the motor neurons affected by the disease and those neurons can not be regenerated again, the current medical method cannot provide an effective treatment for ALS, though we had targeted a therapeutic drug, Riluzole, which was approved by the FDA for ALS clinical treatment. Riluzole cannot prevent the quick progress of ALS, it only can help patients prolong their lives for roughly 3-6 months, according to research. The stem cell therapy is a kind of new technology that can supply ALS patients new motor neurons which carry normal healthy genes after implantation, improve the healthy motor neurons, and slow down/block the further progress of ALS.

From Jan, 2013 to June, 2016, there were 68 ALS diagnosed patients at Wu Medical Center(WMC). The patients were administered three neural stem cell transplants and three mesenchymal stem cell transplants within 2-3 weeks besides the general internal medicine treatment. Doctors had evaluated the patients’ functional changes with ALSFRS before and after the treatment, and monitored the patients’ side effects during the treatment period and their treatment compliance. From the results we could see the patients’ ALSFRS scale increase 5.5 after the treatment, and differences were statistically significant. The side effects during the stem cell treatment period were minimal, there were only 2 cases with a slight fever, 1 case had a headache, while the symptoms were totally controlled after proper medications were given. There was no damage to the organs. The adherence to the medication was better and there were no bad responses reported. The clinical treatment data had fully demonstrated the safety and effectiveness of the combination of the two kinds of stem cells used for the ALS treatment.

Wu Medical Center offered a proposal based on recent years of treatment experience and combined with the specific basic scientific research, the stem cells can be  controlled in vivo artificially more effectively, and doctors can  guide the stem cells to differentiate into the targeted cells according to the actual clinical treatment requirements. In terms of ALS therapy, ALS is a kind of motor neuron system degenerative change caused by gene mutation, the number of neurons decrease gradually, and the patient’s weakness and muscle atrophy worsens day by day, eventually leading to complete paraplegia, even affecting the respiratory system and respiratory failure will eventually occur. Once the CNS(central nervous system) motor neurons are damaged, they cannot regenerative, and while neurological doctors cannot find an effective method for treatment of this condition, doctors at Wu Medical Center have applied stem cells for ALS treatment, increasing the number of motor neurons, enhancing the motor neuron system’s resistance to the pathogenetic factors, repairing the nerve damage, helping patients to recover and improve the muscles’ function, improve the patient’s quality of life and prolong their survival.

To make stem cells work efficiently after implantation, the doctors must be familiar with the cells’ characteristics, use complicated medical technology to regulate and monitor the cells’ growth and work in vivo, use the proper mediation for assistance and use physical rehabilitation training designed according to the instructions of the clinical index. The strict clinical cells regulations will guarantee the real effectiveness of the stem cell treatment, while from past experience, the pure stem cell implantation without cell control treatment could not achieve ideal treatment outcomes, since the existence of the pathology environment, neither the patient’s own motor neurons nor the implanted stem cells (or the neural precursor cells) did not allow the stem cells to survive.

Currently Wu Medical Center has achieved some good progress for ALS treatment, such as doctors discovering that the ALS/MND patient’s abnormal protein accumulation is related to prion protein degeneration, and based on this knowledge, there is an option to treat and improve the motor neurons’ anti-disease fighting ability. For example: motor neurons have prion proteins which are a kind of functional protein. When prion protein gene mutation occurs, there will be a faulty transformation from α-helix to β-pleated sheets, leading to heterodimer formation and a gradual accumulation of abnormal proteins. This can affect neighboring motor neurons via the axon nerves’ conduction and the motor neurons will start the programmed cell necrosis. Wu Medical Center doctors use implanted neural precursor cells which have healthy genes to build internuncial neurons among the genetically mutated nerve cells. They can provide molecular chaperones, and change the methionine into valine, correct the faulty β-pleated sheet transformations, allowing normal nucleoprotein to be produced to heal the nerve cells. The therapy can help patients restore their motor neuron functioning, improve the capability of disease resistance, and provide a new effective method to deal with ALS. However, this therapy requires a series of clinical monitoring and control processes toward the cells in-vivo in order to achieve effective treatment outcome.


Related Information:

Case Analysis for ALS
ALS Patient Stories

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