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

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 2,400+ scientific posters on ePosters
  • More Than 3,700+ 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 TechnologyNetworks.com 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
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
10X Genomics Releases Linked-Read Data from NIST Genome Samples
Genome in a Bottle Consortium data submission for webinar presentation and public availability.
Study Sheds Light on the Causes of Cerebral Palsy
Wider use of genetic testing in children with CP should be considered.
Pitt Researchers to Monitor Resistance to HIV Drugs in Africa
Infectious diseases researchers from the University of Pittsburgh School of Medicine are leading a five-year, $5 million initiative to monitor drug resistance during the rollout of HIV prevention drugs in sub-Saharan Africa.
Environmental Epigenetics Affects Disease, Evolution
Researchers say environmental factors are having an underappreciated effect on the course of disease and evolution by prompting genetic mutations through epigenetics, a process by which genes are turned on and off independent of an organism’s DNA sequence.
Critical New Insights on DNA Repair
The enzyme fumarase is key to reversing genetic damage leading to cancer and therapy resistance.
Potential Treatment for Muscular Dystrophy
A new method for producing muscle cells could offer a better model for studying muscle diseases, such as muscular dystrophy, and for testing potential treatment options.
Nanoparticles Used to Breach Mucus Barrier in Lungs
Proof-of-concept study conducted in mice is a key step toward better treatments for lung diseases.
New Biosensors for Managing Microbial ‘Workers’
Researchers at Harvard’s Wyss Institute have unveiled new biosensors that enable scientists to more effectively control and 'communicate with' engineered bacteria.
Researchers Identify Protein in Mice that Helps Prepare for Healthy Egg-sperm Union
Protein RGS2 plays a critical role in preserving the fertilizability of the ovulated egg.
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!