Possible new drug for children with progeria
Hutchinson-Gilford Progeria Syndrome. HGPS is a childhood disorder caused by mutations in one of the major architectural proteins of the cell nucleus. In HGPS patients the cell nucleus has dramatically aberrant morphology (bottom, right) rather than the uniform shape typically found in healthy individuals (top, right). Image: PLoS Biology Vol. 3/11/2005, e395 (via Wikipedia)
(Medical Xpress) -- A new study published in the journal Science Translational Medicine shows that rapamycin and its derivative everolimus, which is currently used to treat cancer and transplant rejections, may work to reverse the aging effects seen in children with Hutchinson-Gilford progeria syndrome, better known as simply progeria.
Progeria is a rare and fatal genetic disease that affects children and causes rapid aging. It is caused by a defect that affects the processing of the protein lamin A which is responsible for shaping a cells nucleus. The cells instead produce a large amount of progerin, or an abnormal form of lamin A, which causes a disruption to the cells. A buildup of this progerin in the body affects the normal development of tissues in the body. The disease is usually fatal by age 12.
Led by Francis S. Collins, the director of the National Institutes of Health, a team of researchers looked at everolimus and its effects on the mutant protein progerin. Progerin is a protein that is found in everyone as they age, not just in children with progeria. Their original research showed that everolimus was able reduce progerin in healthy individuals and showed the ability to prolong cell life.
The research shows that the everolimus seems to boost the cells internal recycling system to eliminate the progerin as much as 50 percent. The researchers believe that these findings provide enough data to begin clinical trials on children with progeria. In the laboratory, the drug was administered to cells from progeria patients and the progerin protein in the cells disappeared.
In November of 2010, the FDA approved Afinitor, a brand-name everolimus tablet, for the treatment of benign brain tumors. The approval was based on a trial conducted at the Cincinnati Childrens Hospital Medical Center, so the drug has been tested on children before. The hope is they can get quick approval to begin a clinical trial on children with progeria.
This is not the first drug being tested on children with progeria, though the other three drugs currently in trial work in a different way. They are cancer-fighting drugs called farnesyltransferase inhibitors that may work to prevent the production of progerin. It is the hope of Collins that together these two drugs could provide a significant treatment for children with progeria.
More information: Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells, Sci Transl Med 29 June 2011:
Vol. 3, Issue 89, p. 89ra58. DOI:10.1126/scitranslmed.3002346
Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.
© 2010 PhysOrg.com
- The rare aging disease, Progeria, linked to aging in the general population Sep 07, 2010 | not rated yet | 0
- New insight into 'accelerated aging' disease Sep 13, 2010 | not rated yet | 0
- Stem cells study provides clues to aging Mar 05, 2008 | not rated yet | 0
- Adult stem cell changes underlie rare genetic disease associated with accelerated aging Mar 02, 2008 | not rated yet | 0
- Researchers find new clues about aging Jun 13, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
Diseases, Conditions, Syndromes 1 hour ago | not rated yet | 0
(HealthDay)—Few randomized clinical trials have been done to assess clinical prediction rules for patients with lower back pain, and the trials that have been done are of low quality and do not provide ...
Diseases, Conditions, Syndromes 23 hours ago | not rated yet | 0 |
A new, highly sensitive blood test that quickly detects even the lowest levels of malaria parasites in the body could make a dramatic difference in efforts to tackle the disease in the UK and across the world, according to ...
Diseases, Conditions, Syndromes May 17, 2013 | not rated yet | 0
(AP)—The World Health Organization says a yellow fever booster vaccination given 10 years after the initial shot isn't necessary.
Diseases, Conditions, Syndromes May 17, 2013 | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
4 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
1 hour ago | not rated yet | 0
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
12 hours ago | 5 / 5 (1) | 0
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
3 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
13 hours ago | 5 / 5 (1) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
21 hours ago | 3.7 / 5 (3) | 0 |