Aging is a leading risk factor for a number of debilitating conditions, including heart disease, cancer and Alzheimer's disease, to name a few. This makes the need for anti-aging therapies all the more urgent. Now, Salk Institute researchers have developed a new gene therapy to help reduce the aging process.
The findings, published on February 18, 2019 in the journal Nature Medicine editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeny syndrome, a rare genetic disorder that also affects humans. This treatment provides important insight into the molecular pathways involved in accelerated aging, as well as how to reduce toxic proteins through gene therapy. "" Aging is a complex process in which cells start to lose their functionality, so it is critical for us. to find effective ways to study the molecular drivers of aging, "says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and senior author of the paper. "Progeria is an ideal aging model because it allows us to intervene, refine and test it again quickly." With early onset and fast progression, progeria is one of the most severe forms of a group of degenerative disorders. caused by a mutation in the LMNA gene. Both mice and humans exhibit many signs of aging, including DNA damage, cardiac dysfunction and dramatically shortened life span. The LMNA normally produces two similar proteins inside a cell: laminar A and laminar C. Progeria shifts the production of lamin A to progerin. Progerin is a shortened, toxic form of laminates, which accumulates with age and is exacerbated in those with progression.
" "says co-first author Hsin-Kai Liao, a staff researcher in the Izpisua Belmonte lab. "We reasoned that progeria could be treated by CRISPR / Cas9-targeted disruption of both lamin A and progerin."
An adeno-associated virus (AAV) was injected containing two synthetic guide RNAs and a reporter gene. The guide RNA ushers the Cas9 protein to a specific location on the DNA where it can make a cut to render laminate A and progerin nonfunctional, without disrupting laminate C. The reporter helps researchers track the tissues that were infected with the AAV. Two months after the delivery of the therapy, the mice were stronger and more active, with improved cardiovascular health. They showed degeneration of a major arterial blood vessel and delayed onset of bradycardia (an abnormally slow heart rate) ̵
"Once we improve the efficiency of our viruses to infect a wide range of tissues, we are confident that we will be able to increase life span further, "says Pradeep Reddy, a postdoctoral fellow in the Izpisua Belmonte lab and an author of the paper. physiological health and life span or progeria mice. These results provide a significant new understanding of how scientists may eventually be able to target molecular drivers of aging in humans.
Future efforts will focus on making the therapy more effective and will refine it for human use. Currently, there is no cure for progeria, so are symptoms that are treated as they arise.
"This is the first time that has been applied to treat progeria syndrome," says Izpisua Belmonte, holder of the Roger Guillemin Chair. "It will need some refinements, but it has few negative effects compared to other options available. This is an exciting advancement for the treatment of progeria." Source Source:
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