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Huntington Disease

Author Zhangqi Views Posted at 2015/07/10

Case analysis for Huntington Disease(2015-6-18)

Like Wu, Xiaojuan Wang, Bo Cheng, Susan Chu,
Wu Medical Center

The patient was a 43 years old man. He presented with progressive choreic movements of whole body and cognitive abnormality for 10 years. He was diagnosed with Huntington Disease. He had involuntary movement and choreic movements without a cause for 10 years ago. He always hits the people around. He was diagnosed with Huntington Disease after gene test, untreated. The disease got worse. He had choreic movements of limbs, trunk, face and head, accompanied with balance disturbance, dysphagia, dysarthria, and inarticulate of speech. In recent 2 years, he had cognitive dysfunction, hypomnesis, slow in calculation and had intermittence insanity, irritability and aggressive behavior. He could only take care of himself sometimes. His diet was good. He depends on pills to sleep. His urination and defecation were normal. His body type was normal. His three family members died due to this disorder. His was alert and good spirit. His reaction was not good. His memory, calculation and orientation abilities decreased. His head, neck, shoulders and limbs had choreic movements. The muscle tension and muscle power of four limbs were normal. The pathological sign of lower limbs was positive. The finger-nose test, finger-to-finger test and rapid rotation test could not to be done. His lower limbs’ heel-knee test were done clumsy and rough. The rombergs sign was positive. He was diagnosed as Huntington Disease.

Treatment target: Improve the environment in vivo, and to protect cell membranes from being attacked by free radicals and excitatory amino acid. Together with nourishment of the neurons, protecting the normal nerves and regulating the immune to prepare the environment for treatment. 2. Initiate the nerve fixing and regeneration, activate the stem cells in the patient’s body to finish the part of self-repair. 3. During the 3-week treatment, we gave the patient 4 times neural stem cells (NSCs) and 4 times mesenchymal stem cells (MSCs) implantation treatment. This accompanied with medication in order to guarantee the normal cell’s position and function expression. 5. The daily rehabilitation training was incorporated to accelerate the cell differentiation and functional expression.

Treatment results: After the treatment, his emotion was stable. He calm. He could take the drugs. He finished the rehabilitation training. His memory, calculation and balance was better. The choreic movements of his limbs and trunk reduced. He could do the finger-nose test, finger-to-finger test and rapid rotation test. The concordant of lower limbs was better, he could walk better.

Case analysis: Huntington´s Disease (HD) is a kind of genetic-associated degenerative disorder. It is a kind of multiplex brain nerve degenerative disorder. It is autosomal dominant inheritance which causes basal ganglia and pallium degenerative disorder. The clinical symptom: the disorder onset in middle age, Triad: chronic progressive choreic movements, abnormality in behavior and cognitive abnormality. Pathological changes of HD is specificity and selectivity brain nerve degenerative. The most visible changes, initially, are caudate nucleus, dorsal caudate putamen, and later followed by degeneration of cerebrum, thalamus, hypothalamus and globus pallidus, etc. The main symptom is due to severe loss of enkephalin and gamma-aminobutyric acid (GABA ) and the glia cell proliferation. HD is a hereditary disorder. The elements of neuron loss are numerous, the main is variant huntington gene. The gene which contains many proteins copied by amino acids (glutamino). The normal HD protein contains 10 to 25 pieces of glutamino sequences. However, if there are more than 36 pieces of gultamino in HD protein, the shape of the protein will change, and the newly-changed protein will form a huge cluster in the neurons. This will kill the cells in the brain striatum, which will result in a loss of coordination and dementia. The early pathological changes are in caudate nucleus, lenticular nucleus and relational fibers, then it will be in frontal lobe and parie-tal lobes.

Because the nerves decreasing could not be revived, so there is no method of treatment in later stages. Wu Medical Center(WMC) found a new plan to treat this disorder. WMC concluded that nerve replacement was a new efficacious method to treat HD in 15 years’ research. In the research, WMC found that when the patient’s neurons in the striatum become less, loss in the medullated fibers, and the replacement of these cells by fibrous astrocyte. Based on this pathologic changes, the plan to treat this patient including: 1. We could implant stem cells through cerebrospinal fluid circulation. It is closer when the NSCs get to lenticular nucleus and caudate nucleus from the brain cavity wall than from cranium and brain mantle, this could reduce risks. 2. Cell localization method: the basis is, neurons in lenticular nucleus-caudate nucleus is receded and the horizontal cell replaces it. Horizontal cell is a kind of scar-tissue cells, it has no function, but it can turn into epithelioid cell under specified conditions. This characteristic can be used to soften the scar tissue in lenticular nucleus-caudate nucleus area with medicine. During this process, there are multiple cell factors being released, push the implanted stem cells and move to the area around the nidus. Our center have found migration factor and has related it to Fas/FasL. 3. NSCs can differentiate tissues when they get to the location, but it also need to control it with medicine to make them differentiate into small nerve cell, dendrite, acanthi and large pyramidal cell. The best is to differentiate into functional target cell. 4. Treatment results: make the dopamine receptor insensitive, control abnormal movements and avoid getting tardive dyskinesia. The new nerve cells’ secretory function can correct the biochemical irregularity in brain, improve the patient’s behavior, mental and intelligence. The new nerve can remove and stop the HD protein getting together. So the motor function turn better without the side effect of dopamine receptor-blocking agent, such as drowsiness, tardive dyskinesia, etc.

The new treatment plan of WMC makes the HD a manageable disease. NSCs transplant can prolong HD patients’ life and provide some relieve to some degree. This treatment plan can not cure HD forever, but it can prolong a patient’s life. WMC has the advanced NSCs transplanting technology, NSCs and MSCs therapy. The implanted NSCs can significantly increase the number of normal nerve cells and promote nerve repair and differentiation. At the same time, the NSCs can produce growth factors to protect the damaged nerve cells. We observed the visible therapeutic efficacy and the patient’s life have shown some improvement. Stem cell treatment is a new way to treat HD and this brings hope to patients with this disease. Formulate rehabilitation for inpatients based on the patient’s age, incidence time, clinical symptom’s relative, pathological condition and WMC’s treatment data. It’s the new efficacious treatment method of the disease. This new method is a complex treatment and need the newest clinical technology to control. Include: 1.Improve the patient’s clinical symptom and the tissue’s pathological environment. This will contribute to the cells regeneration.2. NSCs located accurately, through diseased region signals induce gradient and get the lesion areas with neurotrophic factor concentration.3. The cells differentiate into targeting cells, so drugs we have can get the target.4. The expressive function of cells: even stem cell differentiates into that cell, it can’t express functionally in pathologic environment. We must use cell control technology to get a good result, get the right point of treatment and research only if we take subtle individual treatment plan. We have treated more than 15 patients and follow-up for 6 months. We found out that the disease was controlled and the motor function was better. That, for these reasons NSCs is a new way to manage the HD.


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