Navigation Links
U. Iowa researchers improve Huntington's disease symptoms in mice

Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine have taken another step toward a potential treatment for Huntington's disease (HD). Using an approach called RNA interference (RNAi), the scientists reduced levels of the disease-causing HD protein in mice and significantly improved the movement and neurological abnormalities normally associated with the disease.HD is a devastating, inherited, neurodegenerative disease that is progressive and always fatal. The disease-causing gene produces a protein that is toxic to certain brain cells, and the subsequent neuronal damage leads to the movement disorders, psychiatric disturbances and cognitive decline that characterize this disease.

"Many of the current approaches aimed at treating HD are indirect and target the symptoms of the disease. RNA interference gives us the first opportunity to attack the fundamental problem and reduce protein expression from the disease gene," said Beverly L. Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "Our study is the first demonstration that a therapy designed to inhibit protein production has a beneficial effect."

The study will appear this week in the Online Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org). Davidson is the senior author and Scott Harper, Ph.D., a postdoctoral researcher in Davidson's lab, is lead author.

Harper, Davidson and their colleagues used RNAi to treat a mouse model of HD. Viral vectors (stripped-down viruses) carrying the genetic instructions to make a RNA interference molecule were injected into the brains of genetically engineered mice before the disease symptoms appeared. The treated mice showed nearly normal movement, and the characteristic neurological damage also was significantly improved in comparison to untreated mice.

Detailed examination of the protein levels in the treated mice showed that levels of the toxic HD protein were reduced to about 40 percent of the level seen in untreated mice.

"It is very exciting that a partial reduction is sufficient to produce a very beneficial effect in the animal. It means that we don't have to turn the gene off completely," Davidson said. "For a disease that takes decades to develop, a partial reduction may slow down the disease-causing copy of the gene to such an extent that either disease progression is delayed or possibly even disease onset is prevented."

It may even be the case that a partial reduction of toxic protein levels allows the brain cells' machinery to "catch up" with the disease-causing protein and clear out the damage caused by the mutant protein.

The genetically engineered or transgenic mouse model used by the UI team carries a section of the human HD gene. These mice quickly develop movement and coordination abnormalities and they die young. Aggregates, or clumps of protein, also develop in certain brain cells.

Davidson explained that this mouse is very good for proof-of-principle experiments, allowing the researchers to ask a very pointed question ?can RNAi improve HD-like symptoms in a mouse model in short order?

"Since our results are positive, we can now repeat the experiment in mouse models that develop disease more slowly and more closely resemble HD in humans," Davidson said.

Most genes are inherited as a pair, one from either parent. In HD, one mutated copy of the gene is sufficient to cause the disease. However, the normal Huntington gene produces a protein that is known to be critical in embryonic development. It is not known if the protein is critical in adult brain cells.

The RNAi molecule used in Davidson's current study would silence both the mutant and the normal gene. So, an important question that still needs to be addressed is whether adult neurons can tolerate and benefit from a partial reduction of both the toxic and the normal protein. If the normal protein is critical, then RNAi will need to be specifically targeted against the disease-causing gene.

Fortunately, RNAi is exactly the right tool to provide an answer regarding whether the normal gene is critical by silencing the normal gene in adult brain cells of HD models.

Despite the remaining hurdles, Davidson is optimistic about the potential of RNAi to treat HD and similar neurodegenerative diseases.

"If the benefit is confirmed in other mouse models of Huntington's disease, and it appears that we don't need to target the RNAi specifically to the disease-causing mutant gene, then I would think it might move to human testing within several years," she said.


'"/>

Source:University of Iowa


Related biology news :

1. NYU researchers simulate molecular biological clock
2. Vital step in cellular migration described by UCSD medical researchers
3. ASU researchers finds novel chemistry at work to provide parrots vibrant red colors
4. UCSD researchers maintain stem cells without contaminated animal feeder layers
5. Why do insects stop breathing? To avoid damage from too much oxygen, say researchers
6. New protein discovered by Hebrew University researchers
7. First real-time view of developing neurons reveals surprises, say Stanford researchers
8. Agilent Technologies releases automated literature search tool for biology researchers
9. Self-assembled nano-sized probes allow Penn researchers to see tumors through flesh and skin
10. Yale researchers identify molecule for detecting parasitic infection in humans
11. US life expectancy about to decline, researchers say
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/29/2016)... 2016 LegacyXChange, Inc. (OTC: ... SelectaDNA/CSI Protect are pleased to announce our successful effort ... variety of writing instruments, ensuring athletes signatures against counterfeiting ... from athletes on LegacyXChange will be assured of ongoing ... Bill Bollander , CEO states, "By ...
(Date:3/21/2016)... March 22, 2016 Unique ... passcodes for superior security   ... provider of secure digital communications services, today announced it ... and offer enterprise customers, particularly those in the Financial ... and voice authentication within a mobile app, alongside, and ...
(Date:3/15/2016)... March 15, 2016 Yissum Research Development ... technology-transfer company of the Hebrew University, announced today the ... sensing technology of various human biological indicators. Neteera Technologies ... million from private investors. ... the detection of electromagnetic emissions from sweat ducts, enables ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... ... ... After several promising treatments in Panama using stem cell ... in Panama, a 6 year-old Duchenne’s muscular dystrophy patient received his first umbilical ... approval of a second application for a single patient, investigational new drug (IND) ...
(Date:5/26/2016)... ... May 26, 2016 , ... FireflySci has been manufacturing quartz ... all over the globe. Their cute firefly logo has been spreading to more ... makes spectrophotometer calibration standards that never require recalibration. These revolutionary standards have ...
(Date:5/25/2016)... ... May 25, 2016 , ... Thailand’s Board of Investment’s New ... San Francisco. Located at booth number 7301, representatives from the Thai Government, research ... the Thai biotechnology and life sciences sector. , Deputy Secretary General of ...
(Date:5/25/2016)... ... 25, 2016 , ... Founder of the Fitzmaurice Hand Institute ... surgery of the hand by the National Board of Physicians and Surgeons, as ... beyond in his pursuit of providing the most comprehensive, effective treatment for his ...
Breaking Biology Technology: