Premature Aging Drug, Rapamycin, Shows Promise For Progeria Patients As Well As Extending Human Life

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Main Category: Pediatrics / Children's Health
Also Included In: Genetics;  Seniors / Aging;  Cardiovascular / Cardiology
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Nicknamed the "forever young drug", Rapamycin, which was created from a substance found in the soil of Easter Island, has been found to have potential for reversing the effects of premature aging, and could even help extend our lifespans by ten years, researchers reported in Science Translational Medicine.

Rapamycin, also known as Sirolimus, is an immunosuppressant medication used to prevent rejection after organ transplantations. It is commonly used after kidney transplants. It is a macrolide antibiotic and was first discovered in Rapa Nui, Easter Island, hence its name. It is a product of the bacterium Streptomyces hygroscopicus. It was originally developed as an antifungal agent. However, as soon as its immunosuppressive and cell growth inhibiting (antiproliferative) properties were discovered, scientists focused on those two areas instead. In laboratory experiments, it has been shown to extend the lifespans of mice. Experts believe it may also be useful for treating certain cancers.

In this latest study, Rapamycin was used on children with HGPS (Hutchinson-Gilford Progeria Syndrome), a devastating genetic condition in which the child ages quickly and reaches old-age by the time they are 12 years old. The accelerated aging is caused by an accumulation in every cell in the body of a protein called Progerin.

The scientists explained that Rapamycin got rid of the progerin in the cells, leaving them healthy.

HGPS is a very rare disease. According to the NIH (National Institutes of Health), approximately 100 cases have been documented over the last 100 years.

Co-author and NIH Director Dr. Francis Collins, said:

"We found it pretty exciting that this drug has such a profoundly positive effect on cell cultures. The ability to understand the molecular basis [of diseases] and develop targeted therapies makes this a very exciting time to be a physician."

The researchers concluded in an Abstract in the journal:

"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."

Progeria affects children, who age much faster than they should. There are different forms of Progeria; Hutchinson-Gilford Progeria Syndrome (HGPS) is the most common. The condition was first described in an academic journal in 1886 by Dr. Jonathan Hutchinson (England), and then in 1897 by Dr. Hastings Gilford (England).

It is estimated that between 1 newborn in every 4 to 8 million has Progeria. Both sexes have the same risk. Progeria rates appear to be the same all over the world, regardless of race, geographical location, or ethnic group.

Babies with Progeria are born looking healthy. At the age of about 10 to 24 months they start showing signs of accelerated aging, which may include: Aging skinFailure to growGeneralized atherosclerosisHair lossJoint stiffnessLoss of body fatHip dislocationStrokePatients with Progeria die between 8 and 21 years of age (average 13 years). Virtually all patients die from heart disease. Patients commonly have cardiovascular problems, such as angina, stroke, hypertension (high blood pressure), enlarged heart, and heart failure - all of them are conditions associated with aging.

Experts have always said that any breakthrough in Progeria treatment would probably have results which would also benefit adults with diseases associated with aging.

Specialists say that it is unlikely that Progeria is an inherited disease. It is probably due to a rare genetic change which happens randomly. Non-twin siblings of a child with Progeria have the same risk of developing the condition as any other child outside the family. However, in approximately 1 in every 100 cases of HGPS, the syndrome may be passed down to the next generation.

"Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells"
K. Cao, J. J. Graziotto, C. D. Blair, J. R. Mazzulli, M. R. Erdos, D. Krainc, F. S. Collins
Sci. Transl. Med. 3, 89ra58 (2011).

Written by Christian Nordqvist
Copyright: Medical News Today
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Treatment Approach To Human Usher Syndrome

Main Category: Eye Health / Blindness
Also Included In: Genetics
Article Date: 02 Jul 2011 - 0:00 PDT window.fbAsyncInit = function() { FB.init({ appId: 'aa16a4bf93f23f07eb33109d5f1134d3', status: true, cookie: true, xfbml: true, channelUrl: 'http://www.medicalnewstoday.com/scripts/facebooklike.html'}); }; (function() { var e = document.createElement('script'); e.async = true; e.src = document.location.protocol + '//connect.facebook.net/en_US/all.js'; document.getElementById('fb-root').appendChild(e); }()); email to a friend   printer friendly   opinions  

New treatment approach shall soon be ready for use in Usher syndrome patients / Publication in "Human Gene Therapy".

Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day life. While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease.

In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options. Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA base, resulting in premature termination of protein synthesis.

The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal "Human Gene Therapy". The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.

"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.

Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.

Sources: Universität Mainz, AlphaGalileo Foundation.

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Treatment Approach To Human Usher Syndrome

Main Category: Eye Health / Blindness
Also Included In: Genetics
Article Date: 02 Jul 2011 - 0:00 PDT window.fbAsyncInit = function() { FB.init({ appId: 'aa16a4bf93f23f07eb33109d5f1134d3', status: true, cookie: true, xfbml: true, channelUrl: 'http://www.medicalnewstoday.com/scripts/facebooklike.html'}); }; (function() { var e = document.createElement('script'); e.async = true; e.src = document.location.protocol + '//connect.facebook.net/en_US/all.js'; document.getElementById('fb-root').appendChild(e); }()); email to a friend   printer friendly   opinions  

New treatment approach shall soon be ready for use in Usher syndrome patients / Publication in "Human Gene Therapy".

Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day life. While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease.

In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options. Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA base, resulting in premature termination of protein synthesis.

The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal "Human Gene Therapy". The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.

"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.

Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.

Sources: Universität Mainz, AlphaGalileo Foundation.

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Privacy Policy | Terms and Conditions

MediLexicon International Ltd
Bexhill-on-Sea, UK
MediLexicon International Ltd © 2004-2011 All rights reserved.

View the original article here

Read More ..