Dr. Like Wu, Dr. Xiaojuan Wang
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.
The diagnosis for this patient is ALS (amyotrophic lateral sclerosis).
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 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.