Navigation Links
Cold Spring Harbor Laboratory scientists devise potential approach to treat spinal muscular atrophy
Date:4/4/2008

Cold Spring Harbor, NY In the neuromuscular disease called spinal muscular atrophy, or SMA, a protein deficiency caused by a single gene mutation leads to serious damage in growing nerve cells and the muscles they control.

Now, in laboratory experiments, researchers at Cold Spring Harbor Laboratory (CSHL) and Isis Pharmaceuticals have induced cells to replenish the protein by activating an existing, slightly modified copy of the mutant gene. These early results hold out hope for one day successfully treating this often-fatal disease.

SMA, which affects about one out of every 6,000 newborns, occurs when the baby inherits a defective version of a gene called SMN1 from both its mother and father. The protein that this gene produces performs cellular "housekeeping" activities, says CSHL professor Adrian Krainer, Ph.D., who led the research team, so "it's hard to explain why it matters more in motor neurons" that are afflicted by SMA than in other cells.

A Backup Copy

Some SMA patients are affected more profoundly than others, in part because a second version of the gene, SMN2, also produces the protein, and makes up for some of the deficit. "All these patients, although they're missing a critical gene, have this second gene that in healthy people is not necessary," says Dr. Krainer.

Over time, subtle mutations have arisen that make the second gene produce much less of the critical protein, even though it still has all of the pieces needed to make the final protein. Instead, the mutations trigger the cellular machinery to omit one major piece of the protein, without which it rapidly degrades.

Researchers have known for years that some sections of the genetic information are left out during the intricate process that ends in the production of protein. The first step of this process, which is called transcription, involves copying DNA into a strand of RNA. This RNA is then edited by special enzymes that remove some sections and splice the others back together before the RNA is used to make protein. For many genes, the various sections can be mixed and matched, so that a single gene produces more than one kind of protein. Once considered a curiosity, this alternative splicing, of the RNA strand is now viewed as common, says Krainer, who is an expert on the topic.

Alternative Ways of Splicing RNA

When he first learned about SMA, Dr. Krainer says, "I was extremely excited, because I realized that what we knew about splicing could be applied" to the disease. All the researchers needed to do was to alter the splicing of the second copy of the gene to include the missing piece.

Dr. Krainer and his team sought to change the splicing by introducing synthetic molecules, called antisense oligonucleotides or ASOs, that precisely match various sections of the RNA. They reasoned that if these molecules stuck to the right part of the RNA, they might redirect the splicing process in the desired way. The researchers injected promising ASOs into mice that had an added, human version of the SMN2 gene. As they had hoped, the gene produced much more of the RNA for the critical protein, including the section that is usually omitted, in tissues where the ASOs accumulate.

Before this approach can be tried in patients, several additional issues must be addressed. Researchers will also need to find out, for example, whether the ASOs really benefit growing animals with SMA and how and when they should be administered to affect the nervous system. Still, in contrast to approaches that change splicing patterns for many genes, Krainer expects the highly targeted ASOs may have fewer side effects.


'/>"/>

Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

Related biology news :

1. Cold Spring Harbor Protocols features methods to screen genomes and analyze evolution
2. Springer expands publishing partnership with the Biomedical Engineering Society
3. Warmer springs mean less snow, fewer flowers in the Rockies
4. Springer author Carlos M. Duarte awarded Spanish science prize
5. RNA-based methods for developmental studies are featured in Cold Spring Harbor Protocols
6. Cold Spring Harbor Laboratory to play central role addressing key questions in plant biology
7. Hot springs microbes hold key to dating sedimentary rocks, researchers say
8. Humana Press journals now available on SpringerLink
9. Cold Spring Harbor Laboratorys lung cancer research program awarded $100,000 grant
10. Springer launches Tropical Plant Biology
11. Moms obesity during conception phase may set the stage for offsprings obesity risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/15/2016)... 2016 Recent publicized breaches in cyber security ... ways to ensure data security and user authentication in ... Android that ties a user,s mobile number ... a hardware authorization token. Customer service agents who employ ... their KodeKey enabled device to verify their identity.  Companies ...
(Date:1/13/2016)... 2016 http://www.researchandmarkets.com/research/7h6hnn/india_biometrics ... the  "India Biometrics Authentication & Identification ...  report to their offering.  ... the addition of the  "India Biometrics ... & Forecast (2015-2020)"  report to ...
(Date:1/11/2016)... 11, 2016  higi, the leading retail and ... locations, web and mobile, today announced it has ... existing investors. --> ... further innovate higi,s health platform – its network ... – including expanding services and programs to retail ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Feb. 11, 2016  Vermillion, Inc. (NASDAQ: VRML ... today announced the formation of the Steering Committee for ... --> Pelvic masses can present physicians ... management. Once pregnancy is ruled out, pelvic masses may ... advanced endometriosis, benign ovarian tumors and gastrointestinal and urinary ...
(Date:2/11/2016)... 2016  Wellcentive today announced it has been ... -based community care organization (CCO) with more ... quality reporting and care management solutions and services. ... of quality managers, analysts and care managers while ... serving FamilyCare members. Oregon ...
(Date:2/11/2016)... 2016   BioInformant announces the February 2016 ... Products, Opportunities, Tools, and Technologies – Market Size, Segments, ... The first and only ... industry, BioInformant has more than a decade of historical ... by stem cell type. This powerful 175 page global ...
(Date:2/10/2016)... Febr. 10, 2016 /PRNewswire/ - BioAmber Inc. (NYSE: BIOA ... announce that Mitsui & Co. Ltd., its partner in ... plant, is investing an additional CDN$25 million in the ... stake from 30% to 40%.  Mitsui will also play ... produced in Sarnia , providing dedicated ...
Breaking Biology Technology: