A New Potential Treatment for Progeria

The accelerated aging condition Hutchinson-Gilford Progeria Syndrome (HGPS) is not in fact accelerated aging, but only appears that way. It is caused by dysfunctional lamin A, a protein vital to nuclear structure in cells, and this dysfunction leads to all sorts of cellular issues and damage. Malformed lamin A does show up in normal aging in very small amounts, but it is unclear whether or not this is significant in comparison to other causes of aging, and whether it is a primary or secondary effect. Researchers have also managed to extend life in mice by manipulation of lamins, which is intriguing but may not be relevant to either human aging or progeria as the mechanisms of action are not yet fully understood. Still, all told it seems worth keeping an eye on progress in the development of treatments for progeria:

In cells from people with HGPS, the nucleus is marked out because, unlike a normal cell's round nucleus, HGPS cell nuclei are drastically misshapen. Scientists believe this makes the cells more fragile, contributing to HGPS patients' symptoms. Proteins called Lamin A and Lamin C play a vital role in nuclear architecture, acting as 'scaffolding' for the nucleus. In HGPS, however, mutations in the gene that makes these proteins mean they cannot shape the nucleus correctly.

[Researchers] found that one compound - which they were able to improve, yielding a molecule that they have named Remodelin - effectively improved the damaged nuclei, restoring their shape. Further tests revealed that doing so also improved the health of the cells, making them grow and divide more normally. "Most drugs work by binding to something in the cell, so we went fishing. We attached a chemical 'hook' to Remodelin, incubated it with cell extracts, and examined what was attached to it when we reeled it back in." The target they fished out was NAT10, a protein not previously associated with ageing or HPGS. "From our following work, we now know that Remodelin works by inhibiting NAT10, so we have gone from finding a potential drug to identifying its target and mechanism-of-action."

The next stage of the research, which is already underway, is to see if Remodelin works in animal models of the disease; if it does, the researchers will be able to trial the drug in patients.

Link: http://www.cam.ac.uk/research/news/remodelling-damaged-nuclei-could-lead-to-new-treatments-for-accelerated-ageing-disease


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