Memantine – Potent Treatment For Huntington’s Disease

Researchers from the Burnham Institute for Medical Research, Burnham, the University of British Columbia’s Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have discovered that normally occurring synaptic activity in the nerve cells – i.e., the electrical activity in the brain that facilitates communication in between the nerve cells, safeguards the brain from the dysfunctional proteins related to Huntington’s disease. On the other hand, unwarranted extrasynaptic activity (anomalous electrical activity in the brain, generally not related to inter-cell communication) augments the misfolded proteins’ lethal outcomes.

Investigators additionally detected that the drug Memantine, that has received approval for treatment of Alzheimer’s disease, ably treated Huntington’s disease in a mouse model by preservation of the normally occurring synaptic activity and repressing uninhibited extrasynaptic activity.

Huntington’s disease is a genetic condition occurring due to a mutation in the huntingtin gene that produces a misfolding and hence dysfunctional or impaired protein. The novel research reveals that normal synaptic receptor activity leads to greater resistance in the nerve cells to the altered proteins. Yet, undue extrasynaptic activity was the major contributing factor to augmented nerve cell fatality. The researchers discovered that small dosages of Memantine reduced extrasynaptic activity without impeding defensive synaptic activity.

Dr. Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience and one of the investigators in the study revealed that chronic neurodegenerative disease such as Huntington’s Disease, Alzheimer’s and Parkinson’s Disease were all linked to protein dysfunction. He explicated that for the foremost time, the researchers have shown that electrical activity has a controlling action on protein folding, and if a drug is available that could alter the electrical activity to the appropriate levels, then one could safeguard against misfolding. Additionally, this corroborates that apposite electrical activity is defensive that supports the premise of ‘either using it or losing it’ of brain activity at the molecular level. For instance, this discovery could clarify why epidemiologists have detected that engaging the brain by doing crossword puzzles and other kinds of games could ward off mental decline in ailments such as Alzheimer’s.

In the new-fangled study, investigators formerly examined nerve cell cultures that had faced transfection with altered Huntingtin protein and detected that lowering undue NMDA-type glutamate receptor activity with Memantine and other contenders safeguarded the nerve cells (glutamate receptors are the key elicitors of excitatory electrical activity in the brain but when in excessive amounts could lead to nerve cell fatality, a process known as excitotoxicity). They additionally detected that normal synaptic activity are shielding. Consequently, treatment involving usage of both the lowered and elevated dosages of Memantine on Huntington’s disease model mouse revealed that lesser dosages prove defensive by jamming pathological extrasynaptic activity whereas elevated Memantine dosages promoted the disease progressing as it additionally hampered the shielding synaptic NMDA receptor activity.

Dr. Hayden stated that since long it has been observed that excitotoxicity is an early indicator of Huntington’s disease. But presently, it has been possible to dissect the means by which this occurs, especially laying focus on NMDA receptors located exterior to the synapse. This method has created new-fangled curative prospects for modulating such receptors with potential safeguarding outcome.

A small-scaled clinical trial employing Memantine for Huntington’s disease has also lately been observed to have positive outcomes. The larger-scaled international clinical trials are presently being considered.

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