Corporate Banner
Satellite Banner
Scientific Community
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
Revolutionary Technologies Developed to Improve Outcomes for Lung Cancer Patients
Breath test to detect lung cancer brings oxygen directly to the wound.
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.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Nanocarriers May Carry New Hope for Brain Cancer Therapy
Berkeley lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier.
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
CRISPR-Cas9 Gene Editing: Check Three Times, Cut Once
Two new studies from UC Berkeley should give scientists who use CRISPR-Cas9 for genome engineering greater confidence that they won’t inadvertently edit the wrong DNA.

SELECTBIO Market Reports
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