Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Researchers Demonstrate Promise of Dicerna Investigational Therapy in Preclinical Model of PH1

Published: Friday, July 04, 2014
Last Updated: Friday, July 04, 2014
Bookmark and Share
DCR-PH1 uses proprietary dicer substrate RNAi technology to inhibit enzyme implicated in rare liver disorder.

Dicerna Pharmaceuticals, Inc. has announced the presentation of preclinical data demonstrating the promise of DCR-PH1, the Company's therapeutic candidate for the treatment of primary hyperoxaluria type 1 (PH1), a rare inherited liver disorder that often results in progressive and severe kidney damage.

The research was presented at the 11th International Primary Hyperoxaluria Workshop in Chicago by Eduardo Salido, Ph.D., Professor of Pathology at the University of La Laguna in Santa Cruz de Tenerife, Spain.

The preclinical studies showed that DCR-PH1 provides potent and long-term inhibition of HAO1, a gene implicated in the pathogenesis of PH1. In a genetically modified mouse model of PH1, researchers reported a 97 percent reduction of the HAO1 transcript in the liver after a single dose of DCR-PH1 and a significant reduction in urinary oxalate levels, a key marker of the disease. In mice treated with DCR-PH1, urinary oxalate levels returned to near baseline levels, similar to normal mice.

"Physicians, patients and families managing PH1 currently have limited to no effective treatment for this severe and progressive disease," noted Craig B. Langman, M.D., chair of the workshop and the Isaac A. Abt, M.D., Professor of Kidney Diseases, and Head, Kidney Diseases, at the Ann & Robert H. Lurie Children's Hospital of Chicago and the Feinberg School of Medicine of Northwestern University. "Based on these encouraging preclinical data, we look forward to beginning clinical trials to determine the potential role of DCR-PH1 in the treatment of PH1."

PH1 occurs when a liver enzyme called AGT does not function properly due to a genetic defect, inducing the liver to over-produce a metabolite called oxalate. While oxalate has no clinical effect in a healthy population, it is concentrated in the urine by the kidneys of patients with PH1, forming calcium oxalate crystals that can lead to chronic and painful cases of kidney stones, scarring of the kidney and end-stage renal disease.

DCR-PH1 is engineered to address the pathology of PH1 by targeting and destroying the messenger RNA (mRNA) produced by HAO1, a gene that encodes glycolate oxidase, a protein involved in producing oxalate. By reducing oxalate production, this approach is designed to prevent the complications of PH1.

"Our preclinical studies indicate that inhibition of the gene HAO1 prevents expression of glycolate oxidase, as expected, and may therefore reduce significantly the abnormally high oxalate production found in patients with PH1," commented Dr. Salido. "By blocking production of glycolate oxidase in the liver, DCR-PH1 may prevent the severe kidney damage that is characteristic of PH1."

"Dr. Salido's data lend further support to the use of the Dicer Substrate RNAi technology platform, which we believe improves upon existing RNAi technologies in the treatment of rare, genetically defined diseases involving the liver," stated Pankaj Bhargava, M.D., Chief Medical Officer of Dicerna. "We look forward to initiating clinical trials of DCR-PH1 to validate these preclinical findings in humans."

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Dicerna Initiates Phase 1 Study of DCR-MYC in Patients with Solid Tumors
DCR-MYC is the first Dicer Substrate RNA interference candidate to advance into clinical testing.
Friday, April 18, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos