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Case Analysis : Case Analysis for Amyotrophic Lateral Sclerosis

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, Shengjie Liu

Wu Medical Center(2016-3-10)

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.

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Patient Stories:

Case Analysis : Stem Cell Therapy for Amyotrophic lateral sclerosis

by Drs.Like Wu, Xiaojuan Wang and Bo Cheng

Introduction:

MND/ALS
The motor neuron diseases (MND) are a group of neurological disorders that selectively affect motor neurons. MND includes the following five kinds of clinical types: Both upper and lower motor neuron damage result in amyotrophic lateral sclerosis. The diseases resulted from lower motor neuron damage include progressive spinal muscular atrophy (PSMA) and progressive bulbar palsy (PBP). Upper motor neuron damaged mainly results in primary lateral sclerosis, PLS. ALS the most typical and common type. All over the world, ALS is considered to be synonymous of MND. It is also called Lou Gehrig's disease in the USA.

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.

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. Wu Stem Cell Medical Center (WSCMC) 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.

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


Case Analysis

Paul Xu, Xiaojuan Wang and Like Wu

Patient is a 63 year old male, he was presented as having progressive weakness of his 4 limbs, and continual weight loss for more than 2 years, the patient has had swallowing difficulties for about 3 months. He had to come to our hospital for further treatment. About 2 years ago, the patient had weakness in his arms without any inducement and he had difficulties lifting his arms, his hands could not hold any heavy things, the fingers were rigid, stretching the fingers was difficult, accompanied by marasmus and muscular atrophy, the most severe part was his hands. 3 months later, the patient had weakness of his lower limbs, it was difficult for him to walk, and he had great difficulty walking upstairs. Patient's legs got to be noticeably thinner. In the local hospital, after the neural system examination and EMG test, the patient was diagnosed with ALS. He had taken oral medications such as Riluzole and different kinds of Vitamins, while his condition turned out to be more serious, the patient had weakness throughout his body, he could not walk more than 30 meters, and in the past 3 months, the patient had disturbances in his swallowing and he had choked occasionally, he had to prolong his eating time, if the patient was overtired, he had difficulty breathing.

Patient was healthy before with no family history of this type of disease.

Admission PE:
All vital signs are stable; the patient is peaked, alert, with a low and weak voice, with mild slurring of his speech. The eyeballs can move freely. The masticatory muscles are very weak, and the bilateral soft plates are too weak to live life as normal. The Pharyngeal reflex is normal. He had bilateral atrophy of his tongue muscles, with tremors. His sensory system is normal by examination. He has muscular atrophy in his deltoid muscles, bicipital muscles of the arms, thenar muscles and interosseous muscles. The muscle force of his upper limbs is 3 degrees. Patient had mild muscular atrophy of his lower limbs, muscle force is 4 degrees, and the patient also had mild muscular atrophy of his shoulders, back and chest. There is muscle fibrillation of his upper limbs, with fasciculation. Bilateral biceps reflex (+), triceps reflex (+), patellar jerking of both sides are overly active. Bilateral Babinski signs are positive. Other laboratory tests are normal.

EMG: there are abnormal neurogenic muscular electrophysiological changes of the 4 limbs and sternocleidomastoids. The sensory nerves conduction velocity is normal.

The diagnosis for this patient is ALS (amyotrophic lateral sclerosis).

Treatment plan:
Medications to improve the patient's bodily internal environment and control the anti toxic effects of EAA (excitatory amino acid) and strengthen the neuro-protection function.

Autologous stem cells activation treatment and start the self repairing of neural system damage.

4 instances of neural stem cells implantation by lumbar puncture, a comprehensive medication used to help the proliferation and differentiation of those stem cells, together with professional rehabilitation training to accelerate the stem cell's differentiation and recovery of the bodily functions.

Treatment results:
After 5 weeks of systemic treatment, the patient's movement ability has shown obvious improvements: he can speak much more clearly, his swallowing difficulty and choking have been greatly alleviated, and his difficulty with his breathing has disappeared. His muscular atrophy has improved; the muscular volume has greatly increased. Patient has regained about 3kg of weight and his muscles are much stronger than before. After treatment, the patient could lift his arms much easier, and his hands could hold things much more flexibly. He can now walk much longer distances than before.

Case analysis:
ALS is a kind of deadly neural degeneration disease which can damage a patient’s upper and lower motor neurons. Ten percent of the cases are heredofamilial, and ninety percent are sporadic cases. In general, patients suffering from ALS are middle aged, the disease can develop gradually, and there is a progressive weakness of the 4 limbs, muscular atrophy, difficulty swallowing, and breathing, and eventually the patient will die from respiratory failure or circulatory collapse. The average course of the disease is about 3-5 years. Currently, all of the general neurological treatment has proven to be useless except Riluzole (a kind of anti ALS medication).

Riluzole is known as an antagonist of GluR (glutamic acid receptor), yet it has remarkable effects in regards to prolonging a patient's life, while the Riluzole can neither repair the damaged neurons nor help the proliferation of the neural system, so that it cannot alleviate the patient's symptoms of weakness, or improve the patient's overall quality of life. Most patients cannot endure taking it for a very long period, and discontinue using it.

Up until now, the ideal therapy for ALS was to help the regeneration of neurons: it is well-known that neurons cannot regenerate after injury, but stem cells have great potential to differentiate and proliferate, if we can use those neural stem cells to repair the motor neuron injury, that will block the development of the disease, and help the patient regain more mobility, improve their quality of life and ultimately prolong the patient’s life.

For those ALS patients, the stem cell treatment is not only simply implanting stem cells, the most important factor is to make those implanted stem cells survive and express normal functions in the patient's body. Even after the stem cells implantation, we still need a series of treatments to control and ensure that the stem cells locate properly to the damaged area, medication to help the restoration of the neural scar tissue, rebuild a new neural connection with self neurons allowing them to grow into normal neurons. Only with this comprehensive treatment can the patient fully achieve improvement of the functioning of the neural system. As a patient, suffering from the typical symptoms of ALS, after the successful treatment, can maintain their improved condition for at least 1-2 years. If the patient has any changes in the future, he can come back for another stem cell treatment to reinforce the previous improvements.

Currently, there is still no complete cure for ALS. But, unlike cancer, which is the unlimited/ uncontrolled proliferation of tumor cells, ALS is a kind of motor neuronal damage and loss. To supply some neural stem cells means the slowing down of the development of the disease in a short period, and the patient can regain some of the damage and realize some improvement. We still hope for a new breakthrough in stem cell engineering and stem cell gene engineering, but doctors and researchers still have a long way to go before this is achieved.

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 , Shengjie Liu

Wu Medical Center(2016-3-10)

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.

-------------------------------------------------------------
Patient Stories:

Name : Noor Muhammad Sex : Male Nationality : Pakistani Age : 67Y Diagnosis : 1. Amyotrophic Lateral Sclerosis, ALS 2. Diabetes (type 2) Date of Admission : April 10th, 2017 Treatment hospital/period : Wu Medical Center/20 days Before treatment: 15

Posted at 2017-10-10 by Zhangqi views(0)

Name : Frederick Dane Sex : Male Nationality : Canadian Age : 60Y Diagnosis : Amyotrophic Lateral Sclerosis (ALS) Date of Admission : Feb. 25th, 2017 Treatment hospital/period : Wu Medical Center/14 days Before treatment: The patient tired easily 5

Posted at 2017-09-06 by Zhangqi views(2)

Name : Neil Antony Verner Sex : Male Nationality : British Age : 49Y Diagnosis : Amyotrophic Lateral Sclerosis (ALS) Date of Admission : March 19th, 2017 Treatment hospital/period : Wu Medical Center/14 days Before treatment: Patient had no obvious

Posted at 2017-08-18 by Zhangqi views(6)

Name : Juan Chabla Sex : Male Nationality : American Age : 59Y Diagnosis : 1. Amyotrophic Lateral Sclerosis (ALS) 2. Type 2 diabetes 3. Hypertension level 3 Date of Admission : March 29th, 2017 Treatment hospital/period : Wu Medical Center/15 days B

Posted at 2017-08-18 by Zhangqi views(6)

Name : Zbigniew Borowczyk Sex : Male Nationality : Polish Age : 57Y Diagnosis : Amyotrophic Lateral Sclerosis(ALS) Date of Admission : Feb. 19th, 2017 Treatment hospital/period : Wu Medical Center/14 days Before treatment: In June 2016 the patient

Posted at 2017-08-08 by Zhangqi views(5)

Name : Mr. Karadi Sex : Male Nationality : UAE Age : 55Y Diagnosis : 1. Amyotrophic Lateral Sclerosis (ALS) 2. Type2 diabetes Date of Admission : March 21th, 2017 Treatment hospital/period : Wu Medical Center/16 days Before treatment : The patient f

Posted at 2017-08-08 by Zhangqi views(5)

Name : Fazlur Khan Sex : Male Nationality : American Age : 63Y Diagnosis : 1. Amyotrophic Lateral Sclerosis(ALS) 2. Hypertension 2 degree Date of Admission : June 2nd, 2017 Treatment hospital/period : Wu Medical Center/14 days Before treatment: 1 y

Posted at 2017-08-08 by Zhangqi views(4)

Name : Abdulla Mohamed Hassan A Alameeri Sex : Male Nationality : UAE Age : 59Y Diagnosis : 1. ALS 2. Diabetes (type2) 3. Paroxysmal supraventricular tachycardia Date of Admission : April 21th, 2017 Treatment hospital/period : Wu Medical Center/14day

Posted at 2017-07-20 by Zhangqi views(12)
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