Animal Gene Therapy Shows Promising Results For Progeria
Progeria is a disease that causes premature aging in children. The cause of this illness is unknown but it is estimated that there are more and more children who are born with this congenital illness year after year. It is however known, that progeria is a rare genetic defect; it is characterized by accelerated aging as evidenced by hair loss, joint pains, cardiovascular problems and skin that is thin, fragile and hairless as compared to an elderly adult.
In 2003, a team under Nicolas Levy discovered a gene therapy that is a promising cure for progeria. In 2008, clinical trials with 12 children were started all in the effort of slowing down the characteristic aging effect of progeria. Up to this day, scientists and researchers under Levy are looking into new efforts in countering the effects of the genetic disorder. Collaboration by Levy’s team with the Annachiara De Sandre-Giovannoli at Inserm/Universite de la Mediterranee and also from a team led by Carlos Lopez-Otin at the University of Oviedo have succeeded in making a model that can imitate the effects of progeria in humans. With this developed model, animals like mice can be treated with the progeria gene therapy to check for promising results. This research was published in the Science Translational Magazine last October 26, 2011.
Levy and his team has been working on progeria since 2003 when they have identified a possible cause through the involvement of the nuclear protein coding LMNA gene, lamin A/C. This genetic mutation apparently causes the production of truncated protein which accumulates in the nuclei of cells and thus creates a toxic effect of cell aging and deformation as evidenced in children with progeria. In the year 2008, clinical trials which involved 12 children diagnosed with progeria. Two existing molecules were combined for the treatment namely statins which are prescribed for the treatment and prevention of atherosclerosis and cardiovascular illness and a molecule of aminobisphosphonates prescribed mainly for the treatment of osteoporosis and some forms of cancer. Together, these molecules are meant to reduce the toxicity of progeria ultimately limiting the progress of the disease.
An animal model came to a form of mice which were introduced with a gene mutation equivalent that of progeria in humans. These were produced under the supervision of Bernard Malissen with the use of the IBISA platform from the Marseille-Luminy Center of Immunology. And thus, with the appropriate animal model found, the research study finally began with the mice having progeria compared to characteristics found in humans. The mice model were seen to have growth defects weight loss, bone deformation and various cardiovascular and metabolic abnormalities as typical of a child with the genetic disorder. When the mutation-targeted treatment in place, these were the results seen:
☀After the treatment, the mice showed a high significant increase in life span; from the average 155 days to a maximum 190 days.
☀Research was seen as promising with a retarded development of progeria.
☀Therapeutic trials that involved children will truly be safe and possibly with other pharmacological molecules to treat this genetic disorder.
The teams of Levy and Lopez-Otin are sure to collaborate to translate the clinical results of this study to make trials with children possible. Along with treatment using human models, new and alternative administration channels are also being considered for antisense oligonucleotides which can also be a promising treatment for other genetic illnesses. With a promising gene therapy for this congenital abnormality there will surely be more and more children with progeria who will have renewed hope for a concrete treatment in the future.