Scientists investigate new strategy to treat spinal muscular atrophy in infants Spinal muscular atrophy (SMA) is a genetic disease that can leave infants with weak muscles and trouble breathing. Many with the disease die before age two. To help these patients, doctors need therapies that target the genetic mutation and stop its progression.
May 07, 2018
Now, scientists at the California Institute for Biomedical Research (Calibr) and The Scripps Research Institute have discovered how a potential new drug targets SMA. The research, published recently in the journal Proceedings of the National Academy of Sciences, could guide the development of other drugs for genetic diseases.
In fact, if we can learn more about the drugs in the pipeline for genetic diseases, we can learn more about the diseases themselves, says Kristen Johnson, PhD, a principal investigator at Calibr and co-lead author of the study.
Until recently, patients diagnosed with SMA had no treatment options. The recent approval of a drug called nusinersen, marketed as Spinraza, has given families hope, and now scientists are working to design therapies that could be even more effective.
One potential drug is RG-7916, a small molecule currently in phase 2 clinical trials run by pharmaceutical company Roche (which no had involvement in this study). In the study, Johnson and her colleagues examined molecules similar to RG-7916 to better understand how the drug works.
Understanding the mechanisms behind drugs is so critical for treating the right kinds of patients, Johnson says. Plus, the more you understand about the mechanism of a drug, the better physicians can watch out for possible side effects.
The researchers suspected that to really be effective, RG-7916 would need to target a process called RNA mis-splicing. In addition to causing SMA, RNA mis-splicing is responsible for a family of devastating genetic illnesses, from Hutchinson Gilford progeria syndrome, which causes premature aging, to Menkes disease, which causes severe neurological impairment and often kills patients before age three.
In these diseases, something has gone wrong in the way the cell reads the genome to produce proteins. During this process, threads of genetic information, called preRNA, need to be spliced into useful fragments. In SMA, molecules called splicing silencers mistakenly swoop in, blocking splicing and stopping the production of the protein, called survival of motor neuron (SMN).
Working closely with study co-leader Peter Schultz, PhD, president of Scripps Research, Johnson and study first author Jingxin Wang, PhD, discovered that analogs to RG-7916 indeed targeted the SMN2 pre-RNA sequence that causes SMA. With the drug molecule in place, the pre-RNA sequence became more flexible and is spliced correctly and ultimately leads to the full length SMN protein.
This drug basically allows the equipment that drives splicing which we call splicing enhancers to sit on the preRNA in right location, says Johnson. This causes the right fragmenting of the RNA so it produces the right protein.
RG-7916 also binds to a nearby protein, and this combined pre-RNA and protein binding interaction makes the drug very specific for targeting the SMA mutation.
Roche has also published data showing that RG-7916 is targeting the pre-RNA splicing process. Johnson says the complementary studies are an encouraging sign that RG-7916 is on the right track, although it will still need to pass key toxicology studies and clinical studies. In the meantime, Johnson is excited to see if drugs to target RNA mis-splicing can be designed to help many more patients.
For example, there are less severe forms of SMA that affect older kids and teenagers, but researchers have primarily tested therapies in infants, says Johnson. We could use what we've learned to try to treat other forms of the disease.
There are only a handful of RNA-targeting drug candidates right now, Johnson says. By studying these drug candidates, scientists may be able to better guide the design of future pharmaceuticals and find more clues to what works and doesn't work.
Now that we have more understanding of this class of drugs, could we build a small library of molecules to start tackling some of these other diseases, says Johnson.
The study, Mechanistic studies of a small-molecule modulator of SMN2 splicing, was supported by the National Institutes of Health (grant R01 NS094721).
Rare Diseases Johnson, Kristen Calibr
Most recent headlines
04/08/2024
Dalet, a leading technology and service provider for media-rich organizations, is excited to announce Santiago Solanas as its new Chief Executive Officer (CEO)....
03/06/2024
Dalet, a leading technology and service provider for media-rich organizations, a...
08/05/2024
zweiB updates to latest version of R&S CLIPSTER Specialist in deliverables for cinema, events and trade shows
Rohde & Schwarz, a global leader in broadcast...
07/05/2024
NAB Show 2024
Utah Scientific rocked the 2024 NAB Show in Las Vegas, unveiling two new game-changers in video signal management.
Our primary focus this yea...
07/05/2024
7th May 2024 The nations favourite comedy channel Gold has teamed up with the ma...
07/05/2024
There's something special about summer. We're not sure whether it's the warmer weather, the longer days, or something else a bit more magical, but s...
07/05/2024
NITV appoints Michael Rennie as Presenter and Senior Producer for NITV News
Media releases
NITV has announced the appointment of Michael Rennie as Presenter...
07/05/2024
The ability for line-of-site tactical voice and data networks to seamlessly traverse over Satellite Communications is an emerging requirement to assure warfight...
07/05/2024
On April 5, 2024, the L3Harris Avionics Products Repair Station (NN2R037L) in Gr...
07/05/2024
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({ content_source:......
07/05/2024
Share this article
width=32 height=32 loading=lazy data-lazy-src=https://apogeedigital.com/app/themes/juniper-theme/src/img/icons/facebook-purple.svg />
wid...
07/05/2024
BURBANK, Calif. The Walt Disney Company has finally delivered some from profits from its hefty streaming investments, with the second quarter of its fiscal year...
07/05/2024
Bonnie Hammer, vice chair of NBCUniversal, and Jen Psaki, MSNBC host, read from their new books at the 92nd Street Y in Manhattan Wednesday, May 8. Hammer's...
07/05/2024
Paramount Plus has ordered the series Crutch, a comedy that is a spinoff of CBS comedy The Neighborhood. Tracy Morgan stars....
07/05/2024
Edward J. and Melody Thomas Scott and Lidia Bastianich will receive Lifetime Achievement honors at the 51st annual Daytime Emmy Awards in June, the National Aca...
07/05/2024
The 2024 Giants of Broadcasting & Electronic Arts luncheon and awards ceremony happens in New York November 12, and the honorees are Al Roker, weather and featu...
07/05/2024
Dabl Network has added The Wayans Bros., The Jamie Foxx Show, Living Single and Everybody Hates Chris to its weekday and weekend lineups. Those shows join the l...
07/05/2024
After winning a proxy fight, The Walt Disney Co. said its entertainment business turned a profit and added subscribers in its fiscal second quarter....
07/05/2024
NBA Entertainment is closing out the second season of its series Pass the Rock with a look at Victor Wembanyama of the San Antonio Spurs, the league's rooki...
07/05/2024
Syncbak, which provides stations with streaming capabilities, said it is rebranding as Zeam Media....
07/05/2024
Samsung has made a deal with Magnolia Pictures that will bring titles from Magnolia to the Samsung TV Plus free streaming platform....
07/05/2024
Amazon, which has added commercials to Amazon Prime Video, is rolling out new interactive ad formats that will enable advertisers to engage streamers and sell s...
07/05/2024
Syncbak, a 15 year-old provider of streaming tech for local broadcast stations has rebranded itself, adopting the name of its streaming service launched in Febr...
07/05/2024
POST Luxembourgs journey with TAG Video underscores how finding a vendor who und...
07/05/2024
PORTSMOUTH, N.H. New findings from Hub Entertainment Research provides extensive data showing that the majority of consumers will opt for lower cost ad-supporte...
07/05/2024
NEW YORK The Library of American Broadcasting Foundation (LABF) has announced th...
07/05/2024
CBS News has named Lindsey Reiser an anchor and correspondent for CBS News 24/7, the network's live, streaming news service. Reiser, who was most recently a...
07/05/2024
NEEDHAM, Mass. After more than two years of decline, worldwide tablet shipments posted modest year-over-year growth of 0.5% in the first quarter of 2024 (1Q24),...
07/05/2024
ESPN is reporting that April was a record-setting month as the network delivered its best April prime time audience on record, dating back more than 30 years....
07/05/2024
WASHINGTON, D.C. The National Association of Broadcasters (NAB) has announced that Kirsten Donaldson has joined NAB as vice president of public policy. Donaldso...
07/05/2024
The Bulls are back home again this week from May 7-12! Don't miss out on any...
07/05/2024
SVG Sit-Down: AWS's Julie Souza on the Cloud and AI in Broadcast-Content Cre...
07/05/2024
Deloitte Analysts Peter Giorgio and Michael Vovk: Sports Properties Need To Reth...
07/05/2024
University of Texas' Jeff Hanel to Keynote 16th-Annual SVG College Summit Industry vet to discuss uniting live and creative in athletic department media arm...
07/05/2024
Premier League trials RefCam during Crystal Palace v Manchester United fixture By George Bevir
Tuesday, May 7, 2024 - 09:34
Print This Story
In a Premier ...
07/05/2024
CBS Sports Previews PGA Championship Plans; 125+ Cameras Include FlyCams, Bunker...
07/05/2024
Rohde & Schwarz brings cutting-edge solutions to TECNOSEC and DRONExpo 2024 Rohde & Schwarz will showcase its innovative portfolio at TECNOSEC and DRONExpo 20...
07/05/2024
Back to All News
Five New Games Join Netflix in May
Netflix Staff
Entertainment
07 May 2024
Global
Link copied to clipboard
Five new games are launching ...
07/05/2024
Back to All News
Top 10 Week of Apr. 29: Baby Reindeer' Holds Strong; Hee...
07/05/2024
Home News & Press Blancco Wins 2024 SEAL Business Sustainability Award
Blancco Wins 2024 SEAL Business Sustainability Award May 07, 2024
Blancco's v...
07/05/2024
CUPERTINO, CALIFORNIA Apple today unveiled the all-new Logic Pro for iPad 2 and Logic Pro for Mac 11, delivering breakthrough professional experiences for songw...
07/05/2024
Apple's new Privacy Manifest requirement mandates that apps explicitly disclose the privacy-related data they collect, the purposes for this collection, and...
07/05/2024
Taylor Swift's Eras Tour arrives to shake up EuropeHaving shaken four continents, Taylor Swift's Eras Tour finally brings the biggest pop culture icon o...
07/05/2024
Isiphetho: Destiny' beats Scandal!'E.tv's latest telenovela Isiphetho: Destiny' beat the channel's longest running soapie, Scandal!' ...
07/05/2024
Now there's HELP for ex-prisoners to find work in South AfricaNew initiative for ex-prisoners to find work in South Africa proves it's never too late fo...
07/05/2024
Tonight on Scandal: Cohen is pulled into keeping a secretDon't miss Tuesday, 7 May's riveting episode of South African soapie Scandal! on e.tv on DStv c...
07/05/2024
Skeem Saam: Monday's episode, 6 May 2024 [video]Missed an episode of Skeem Saam? No problem! Watch the latest episode of your favourite South African soapie...
06/05/2024
By Ilyse McKimmie
Now, more than ever
That's a phrase so often used in the last few years that I've come to dread seeing it in notes like this one. A...
06/05/2024
alt= class=wp-image-12099 data-lazy-src=/wp-content/uploads/2024/05/Blog-Exabyte-Storage-Demand-960x540-1.jpg/> Demand for storage solutions has reached unprece...
Scientists investigate new strategy to treat spinal muscular atrophy in infants Spinal muscular atrophy (SMA) is a genetic disease that can leave infants with weak muscles and trouble breathing. Many with the disease die before age two. To help these patients, doctors need therapies that target the genetic mutation and stop its progression.
