Commentary Article: ALS/MND Gene Therapies - Progresses & Limitations - by Wu Medical Center

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 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 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 that it can be repeated when 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.

Authors: Drs. Li-Ke Wu, Xiaojuan Wang, Bo Cheng, Susan Chu, Shuangshuang Liu and Fang Peng