A computational model for the Huntington disease

SummaryHuntington’s disease is caused by degeneration or malfunctioning of basal ganglia. Although the exact pathophysiology of this disease is not clear, it seems that abnormal glutamate release is involved in producing movement disorders.Few simulations are done on Huntington’s disease. Since a complex movement disorder is seen in this disease, a mathematical model is needed to analyze it. We designed a computational model based on physiological findings. The model block diagram is proposed. The glutamate abnormality of the disease is considered as an environment noise and is designated as a random number generator in the model. To designate inhibitory and excitatory effect of neurotransmitters on each block, we used Hill functions.We designated the internal behavior of blocks using a closed loop system. Proper transfer functions are assumed for each block in our model. In order to separate normal and diseased conditions, we included noise in all glutamate related blocks and put it dependent to a parameter, g. All nominal quantities used in the model are chosen by try and error.The response of the model is presented for different values of g in health and illness states. In this study, we have designated g = 1 for healthy and g = 10 for illness states. In the healthy state, our model’s output is zero. However, it produces an abrupt movement in Huntington’s disease, like what is seen in chorea. While reducing g from 10 to 3 causes the size of answer to be reduced, putting the g below 3 will cause cessation of jerky movement.Some of our model’s response properties, as the period between each two abrupt movements, size of movement and the shape of movement curve are completely stochastic, being another significant similarity between our model and the real conditions.According to all similarities between the model and Huntington’s disease, any change in the model parameters can resemble real changes. We evaluated some parameters, as substance P and GABA levels, in the basal ganglia model and showed that increasing these variables are able to ameliorate the patient’s symptoms. We suggest that prescribing drugs such as gabapentin could improve the symptoms. Surely, clinical trials are needed to validate this suggestion.