Researchers at the Rare Diseases Network Biomedical Research Center (CIBERER) at the La Fe Health Research Institute (IIS La Fe) in Valencia have discovered that activating the enzyme AMP-activated protein kinase (AMPK), by means of drugs such as metformin, improves symptoms suffered by animal models…
Researchers at the Rare Diseases Network Biomedical Research Center (CIBERER) at the La Fe Health Research Institute (IIS La Fe) in Valencia have discovered that activating the enzyme AMP-activated protein kinase (AMPK), by means of drugs such as metformin, improves the symptoms suffered by animal models of Huntington’s disease (HD).
In addition, it is a study that is being transferred to practice, through the promotion of a clinical trial, using the double-blind and placebo-controlled method, to investigate metformin as a therapeutic agent to treat HD.
The article, published in the journal ‘Mechanisms of Aging and Development’, reiterates the importance of metformin as a potential therapy against Huntington’s disease and AMPK as a highly useful therapeutic target that could be used, in turn, in other pathologies most prevalent neurodegenerative diseases (Parkinson’s or Alzheimer’s) and that present characteristics similar to HD, such as the aggregation of proteins prone to collapse.
Metformin is an oral antidiabetic drug used to curb excess glucose in the blood. For its part, AMPK is an enzyme complex that is activated by energy drops in the cell, but also by alarm signals produced by different types of stress, including mutant huntingtin.
As explained by the article’s coordinator, Rafael Vázquez, “once AMPK is activated, it triggers other signals and activates ‘cleaning routes’ of defective proteins (autophagy and the proteasome system) that should eliminate the mutant huntingtin from the cellular environment.”
It is common for huntingtin to block these ‘cleaning pathways’ in some HD patients and various animal models. However, it has been shown that activating AMPK through drugs such as metformin causes the reactivation of these pathways and, in turn, an improvement in the symptoms suffered by animal models of Huntington’s disease.
Characteristics of Huntington’s Disease
Thus, this rare disease is characterized by a progressive deterioration of motor and cognitive skills, since it causes the neurons of these regions to stop working and, consequently, patients suffering from this pathology manifest chorea (involuntary movements), motor incoordination, psychiatric disorders and cognitive decline.
Despite the fact that, at present, there is no treatment to slow down or cure the disease, and chorea can hardly be treated with antichoreics and psychiatric problems with common antidepressants, the work carried out in animal models of HD and the cross-sectional studies of patients with the disease, suggest that metformin can benefit people suffering from this hereditary pathology as it is a pleiotropic drug that activates many potential targets to treat it and that, in addition, it reaches almost all the organs and tissues of the human body.