Navigation Links
Mouse study shows gene therapy may be possible cure for Hurler syndrome
Date:2/4/2014

CINCINNATI Researchers used blood platelets and bone marrow cells to deliver potentially curative gene therapy to mouse models of the human genetic disorder Hurler syndrome an often fatal condition that causes organ damage and other medical complications.

Scientists from Cincinnati Children's Hospital Medical Center and the National Institute of Neurological Disorders and Stroke (NINDS) report their unique strategy for treating the disease the week of Feb. 3-7 in Proceedings of the National Academy of Sciences (PNAS).

Researchers were able to genetically insert into the cells a gene that produces a critical lysosomal enzyme (called IDUA) and then inject the engineered cells into mice to treat the disorder. Follow up tests showed the treatment resulted in a complete metabolic correction of the disease, according to the authors.

"Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes," said Dao Pan, PhD, corresponding author and researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed."

The mice tested in the study modeled human Hurler syndrome, a subset of disease known as mucopolysaccharidosis type I (MPS I), one of the most common types of lysosomal storage diseases. MPS I is a lysosomal storage disease in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).

IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints, according to the National Library of Medicine/National Institutes of Health. Without IDUA, sugar molecules build up and cause organ damage. Depending on severity, the syndrome can also cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.

Enzyme replacement therapy can be used to treat the disease, but it is only temporary and not curative. Bone marrow transplant using hematopoietic stem cells also has been tested on some patients with mixed results. The transplant procedure can carry severe risks and does not always work.

Pan and her colleagues including Roscoe O. Brady, MD, a researcher at NINDS report that using platelets and megakaryocytes for gene therapy is effective and could reduce the risk of activating cancer-causing oncogenes in hematopoietic stem cells.

The authors said tests showed that human megakaryocytic cells were capable of overexpressing IDUA, revealing their capacity for potential therapeutic benefit. While engineering megakaryocytes and platelets for infusion into their mouse models of Hurler, the scientists report they were able to release IDUA directly into amply sized extracellular spaces or inside micro-particles as the cells matured or activated. The cells were able to produce and package large amounts of functional IDUA and retained the capacity to cross-correct patient cells.

After infusing mouse models of Hurler with the genetically modified cells, researchers said this led to long-term normalization of IDUA levels in the animal's blood with versatile delivery routes and on-target preferential distribution to the liver and spleen. The treatment led to a complete metabolic correction of MPS I in most peripheral organs of the mice.

Researchers cautioned that study results involving laboratory mouse models do not always translate into clinical treatment of human patients, and that additional research is needed for this prospective therapy.


'/>"/>

Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related biology news :

1. Dietary treatment shows potential in a mouse model of Alzheimers disease
2. The mouse that RORed
3. H. pylori vaccine shows promise in mouse studies
4. New book on mouse models of cancer from Cold Spring Harbor Laboratory Press
5. Mouse studies reveal promising vitamin D-based treatment for MS
6. Elevated levels of copper in amyloid plaques associated with neurodegeneration in mouse models of AD
7. New agent inhibits HCV replication in mouse models -- No resistance seen
8. Cat and mouse: A single gene matters
9. New mouse viruses could aid hepatitis research
10. Omega-3s from fish vs. fish oil pills better at maintaining blood pressure in mouse model
11. UT Southwestern scientists make mouse model of human cancer, demonstrate cure
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/13/2017)... N.Y. , Jan. 13, 2017 ... technology solutions for the homecare industry, including Electronic ... homecare industry expert, Justin Jugs, as Senior Vice ... more than 15 years of homecare experience to ... in developing strategic plans to align Sandata,s suite ...
(Date:1/12/2017)... PORTLAND, Oregon and PUNE, India , January 12, 2017 ... Technology Market: Opportunities and Forecasts, 2015 - 2022," projects that the global biometric technology ... CAGR of 19.4% from 2016 to 2022. Continue Reading ... ... ...
(Date:1/6/2017)... Jan. 6, 2017  Privately-held CalciMedica, Inc., announced ... healthy volunteers of a novel calcium release-activated calcium ... pancreatitis. Acute pancreatitis, sudden painful ... disorder, but can be very serious.  In severe cases ... where extended hospital stays, time in the ICU ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... PA (PRWEB) , ... January 18, 2017 , ... ... operations again at the CHI SCOPE Summit for Clinical Ops Executives (Hyatt Regency ... engaging panel discussions to examine vital clinical research issues such as trial performance ...
(Date:1/18/2017)... ... ... Thirty-six startup companies in University City and Center City have been awarded ... Development in 2016 as part of the Keystone Innovation Zone (KIZ) Tax Credit Program. ... represent the highest number of awards to the largest number of companies in the ...
(Date:1/18/2017)... Jan. 18, 2017  Caris Life Sciences, a ... Foundation, the largest private funder of pancreatic cancer ... evaluating the impact of immunotherapy in the treatment ... enrollment services to identify potential trial candidates based ... treating physicians and study investigators. The Lustgarten Foundation ...
(Date:1/17/2017)... ... January 17, 2017 , ... LGC Maine ... its VALIDATE® SP2 calibration verification / linearity test kit. VALIDATE® SP2 evaluates Albumin, ... VALIDATE® SP2 kit is prepared using the CLSI recommended “equal delta” method for ...
Breaking Biology Technology: