Huntington's disease: modeling the gait disorder and proposing novel treatments.
Huntington's disease is a movement disorder originated from malfunctioning of Basal Ganglia (BG). There are some models for this disease, most of them being conceptual. So, it seems that considering all physiological information and structural specifications to develop a holistic model is needed. We introduce a computational model based on experimental and physiological findings. Parts of the brain known to be involved in Huntington's disease are all considered in our model and most features of the movement disorders have been appeared in the model. This mathematical model has considered the involved parts of the brain in a fairly accurate way, explaining the behavior and mechanism of the disease according to the physiological information. Our model has several advantages. It is able to simulate the normal and Huntington's disease stride time intervals. It shows how the present treatment, i.e. diazepam, is able to ameliorate the gait disorder. In this research we assessed the effects of changing some neurotransmitter levels in order to propose new treatments. Although we showed that gamma amino butyric acid (GABA) blockers reduce Huntington's disease movement disorder, but we discussed that it is unfair to use this route for treatment. We evaluated our model response to increment of GABA, alone and observed that the gait disorder was strengthened. Our novel idea in this regard is resuscitation of BG loop in order to maintain its major physiological functions, and at the same time raising the threshold in order to weaken the internal disturbances. Our last idea about BG treatment is to decrease glutamate. Our model was able to show the effectiveness of this treatment on Huntington's disease disturbances. We propose that experimental studies should be designed in which these two novel methods of treatment will be evaluated. This validation would implement a milestone in treatment of such a debilitating disease at Huntington.
Banaie
Masood
M
Department of Biomedical Engineering, Faculty of Technical Sciences, Shahed University, Iran.
Sarbaz
Yashar
Y
Gharibzadeh
Shahriar
S
Towhidkhah
Farzad
F
D001479:Basal Ganglia / Q000378:metabolism / Q000503:physiopathology; D003198:Computer Simulation; D003975:Diazepam / Q000627:therapeutic use; D018757:GABA Modulators / Q000627:therapeutic use; D005684:Gait; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018757:GABA Modulators; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003975:Diazepam