Navigation Links
Treatment Extends Survival in Mouse Model of Spinal Muscular Atrophy

Drug therapy can extend survival and improve movement in a mouse model of spinal muscular atrophy (SMA), new research shows. The study, carried out at the NIH’s National// Institute of Neurological Disorders and Stroke (NINDS), suggests that similar drugs might one day be useful for treating human SMA.

"This study shows that treatment can be effective when started after the disease appears," says Kenneth H. Fischbeck, M.D., of the NINDS, who helped lead the new study. The finding is important because most children with SMA are diagnosed after symptoms of the disease become obvious, he adds.

SMA is the most common severe hereditary neurological disease of childhood, affecting one in every 8,000-10,000 children. Babies with the most common form of the disease, called SMA type I, develop symptoms before birth or in the first few months of life and have severe muscle weakness that makes it difficult for them to breathe, eat, and move. They usually die by age two. Other forms of SMA are not as severe, but still cause significant disability. While some symptoms of SMA can be alleviated, there is currently no treatment that can change the course of the disease.

SMA is caused by mutations in a gene called SMN1. Investigators studying the genetics of SMA have found that there is another gene, called SMN2, on the same chromosome. While the normal form of SMN1 produces a full-length functional protein, most of the protein produced by SMN2 is truncated and unable to function. The relatively small amount of normal SMN protein produced by the SMN2 gene can reduce the severity of the disease. Therefore, investigators are searching for drugs that can increase the amount of normal protein produced by this gene.

The new study, directed by Dr. Fischbeck's colleague Charlotte J. Sumner, M.D., at NINDS, tested a drug called trichostatin A (TSA) that is in a class of drugs called histone deacetylase (HDAC) inhibitors. These drugs increase the a ctivity of certain genes in the body.

Previous studies have shown that HDAC inhibitors can increase the amount of SMN2 expression in cultured cells and that treating pregnant mice with an HDAC inhibitor can increase the survival of their babies with SMA. Preliminary clinical trials are now underway to test several HDAC inhibitors in children who have SMA. However, the drugs in those clinical trials are weak HDAC inhibitors with other biological effects that may limit their usefulness for treating this disease. More importantly, none of the previous studies has demonstrated that HDAC inhibitors can extend survival when delivered after symptoms appeared.

In the new study, the investigators tested TSA, which is a potent HDAC inhibitor, in cells from SMA patients and in a mouse model of SMA. They found that the drug increased the amount of SMN2 gene activity in both the cultured cells and the mouse model.

Next, the researchers gave daily injections of TSA to the SMA mice, starting when the mice were 5 days old. By that time, the mice showed clear symptoms of disease: they were significantly underweight and they had a markedly impaired righting reflex, or ability to get on their feet after being placed on their backs. The treated mice lived 19 percent longer, on average, than mice that did not receive TSA. About three-fourths of the treated mice had improved survival compared to control mice. The other fourth showed no improvement.

The treated mice had less weight loss and better righting reflexes, walking ability, and forelimb grip strength than mice that did not receive TSA. Examination showed that the TSA-treated mice also had larger neurons in the spinal cord, thicker muscle fibers, and more muscle mass than untreated mice.

"This is a proof-of-concept experiment," says Dr. Sumner. "It clearly demonstrates that this treatment can ameliorate the disease in mice." While the results are exciting, there are still no stud ies that have proven the effectiveness of HDAC inhibitors in humans, she cautions.

The investigators are now testing whether treatment with TSA earlier in the disease process will work better than the delayed treatment in this study. They also plan to test other HDAC inhibitors in mice and to study exactly how the drugs influence the disease process. While TSA is expensive to produce and it is not approved for clinical use, similar drugs being developed to treat cancer and other diseases may be useful for treating SMA, Dr. Sumner says.

Source-Bio-Bio Technology
'"/>




Related medicine news :

1. Advances in Treatment of Cataracts
2. Recommendations for Treatment of Blood Pressue
3. Treatment for Menieres disease
4. Treatment for pre-menstrual syndrome is ineffective
5. Better Treatment for obesity
6. Gene Treatment for Heart Disease
7. More People Seeking Treatment for Depression
8. Focused Treatment For Childhood Cancer
9. Inadequate Drug Treatment For Youth
10. FDA Approves New surgery Treatment for Farsightedness
11. Treatment of antibiotics ineffectual in bronchitis
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/24/2016)... ... June 24, 2016 , ... Puradigm® & Innovative Solutions ... initiated cultivation and processing operations at its production facility, and opened its first ... is the manufacturer of a complete system of proactive air and surface purification ...
(Date:6/24/2016)... ... ... National recruitment firm Slone Partners is pleased to announce the ... as Vice President of North American Capital Sales at HTG Molecular . ... team in the commercialization of the HTG EdgeSeq system and associated reagents in North ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... human induced pluripotent stem (iPS) cells and other difficult to transfect cells, announces ... Medium. The PluriQ™ G9™ Gene Editing System is a complete system ...
(Date:6/24/2016)... ... June 24, 2016 , ... Finally, a bruise cream that ... dermaka cream can be incorporated into the post-surgical treatment plans of a variety of ... , dermaka cream is very effective for bruising and causes a rapid resolution of ...
(Date:6/24/2016)... IL (PRWEB) , ... June 24, 2016 , ... ... Beard, DDS, and Randall Markarian, DDS, are co-chairs for the Illinois State Dental ... clinic Friday-Saturday, July 15-16 at the Gateway Convention Center in Collinsville. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016  In a startling report released today, ... their residents by lacking a comprehensive, proven plan to eliminate prescription ... definitive ranking of how states are tackling the worst drug crisis ... four states – Kentucky , New ... Vermont . Of the 28 failing states, three – ...
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on ... today announced that patient enrollment in its ongoing ... Duchenne) has exceeded 50% of its 24-patient target. ... in the third quarter of 2016, and to ...
(Date:6/23/2016)... , June 23, 2016 , ... on Thursday, July 7, 2016 , , , , LOCATION: ... , , , , EXPERT PANELISTS:  , , , ... Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar and ... The global pharmaceutical industry is witnessing an exceptional era. ...
Breaking Medicine Technology: