Navigation Links
Leap forward in efforts to develop treatments for Huntington's disease
Date:7/28/2010

Scientists at the Buck Institute for Age Research have discovered that a particular family of enzymes are involved in the breakdown of proteins that modify the production of toxic fragments that lead to the pathology of Huntington's disease. These enzymes, matrix metalloproteinases (MMPs), provide new targets for drug therapies for the disease targets that have already been shown to respond to cancer drugs currently in clinical development. Results of the research, from the laboratories of Buck faculty members Lisa Ellerby, Ph.D. and Robert Hughes, Ph.D., appear as the cover story in the July 29, 2010 edition of Neuron.

Huntington's disease (HD) is an incurable progressive neurodegenerative genetic disorder which affects motor coordination and leads to cognitive decline and dementia. Symptoms usually begin to occur in middle age; patients are often totally incapacitated prior to death. The worldwide prevalence of HD is 5-10 cases per 100,000 people; the rate of occurrence is highest in peoples of Western European descent.

The disease stems from a mutation in the huntingtin gene, located on human chromosome four. The mutation causes abnormalities in the huntingtin protein (mutantHtt, or mHtt). The pathology of HD is accelerated when mHtt is cut into smaller, highly toxic fragments via various molecular activities. Dr. Ellerby said to date, scientific queries into how those fragments are cut have focused primarily on caspases, a family of intracellular proteins that mediate cell death, and calpains, enzymes regulated by the concentration of calcium ions. The Buck Institute study involved proteases, various enzymes that catalyze the breakdown of proteins in reaction to water. Dr. Ellerby said this research marks the first time all of the 514 different types of proteases found in humans were individually screened in cell culture to see how they affect mHtt proteolysis. Buck Institute researchers identified 11 proteases that, when inhibited, reduced the accumulation of toxic fragments associated with HD.

Four of the proteases belong to a family called matrix metalloproteinases (MMP), a class of enzymes already involved in drug development, Dr. Ellerby said. "We've found a target that has known drugs for cancer treatment that could possibly have significance for HD," added Dr. Ellerby. "MMPs are also involved in stroke, inflammation and many neurological processes; we expect a lot of scientific attention to now be focused on this important class of proteases," she said.

Results involving MMPs were verified in mouse models of HD, Dr. Ellerby said. In collaborative studies with Dr. Juan Botas at Baylor College of Medicine in Houston, researchers found that homologs of MMPs suppressed HD-induced neuronal dysfunction in fruit flies. "The next step in this research will be to test some of the MMP inhibitor drugs as a potential treatment in HD mouse models," said Dr. Ellerby. "We'll also be crossing mice that no longer have particular MMPs with those who have HD to see what effect that has on offspring," she said.


'/>"/>

Contact: Kris Rebillot
krebillot@buckinstitute.org
415-209-2080
Buck Institute for Age Research
Source:Eurekalert

Related medicine news :

1. An Earth Day View of Green Building: Earth Advantage Institute Looks 10 Years Forward
2. American Physical Therapy Association (APTA) Kicks Off Social Media Campaign to Help You “Move Forward”
3. University of Colorado Hospital Moving Forward with $400 Million Expansion
4. Gene Therapy for HIV Inches Forward
5. Actor and Humanitarian Harrison Ford Assists Operation Smiles Relief Efforts in Haiti
6. Reliv Foundation Donates $450,000 In Nutritional Supplements to Haitian Relief Efforts
7. Businesses Rally Big Efforts to Benefit the Susan G. Komen Phoenix Affiliates Fight Against Breast Cancer
8. Lighthouse To Help Relief Efforts In Haiti
9. JPMA Supports CPSC Chairman Tenenbaum's Continued Safety Efforts
10. ChildCare Education Institute Supports the First Ladys Efforts to Reduce Childhood Obesity
11. Buildium Announces Fundraising Campaign to Benefit Haiti Relief Efforts
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of ... Philippines. “The Journey: From the Mountains to the Mission Field” is the creation of ... taught all ages and currently teaches a class of ladies at her church, which ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and ... apnea using cutting-edge Oventus O2Vent technology. As many as 18 million Americans ... frequent cessation in breathing. Oral appliances can offer significant relief to about 75 ...
(Date:10/12/2017)... ... October 12, 2017 , ... IsoComforter, Inc. ( https://isocomforter.com ... the introduction of an innovative new design of the shoulder pad. The shoulder ... maximum comfort while controlling your pain while using cold therapy. By utilizing ice and ...
(Date:10/12/2017)... ... October 12, 2017 , ... Information about the ... to develop to enable prevention of a major side effect of chemotherapy in ... in pediatric patients. For cisplatin, hearing loss is FDA listed on-label as a ...
(Date:10/12/2017)... , ... October 12, 2017 , ... Leading pediatric oncology ... in Washington, D.C., for the 49th Congress of the International Society of Paediatric ... President of the Center for Cancer and Blood Disorders at Children’s National, ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)... AMSTERDAM , Sept. 25, 2017   ... Trial Master File solutions, today—from the IQPC Trial ... Amsterdam , NL)—announced that EastHORN Clinical Services ... its clinical programs and TMF management. EastHORN, a ... Montrium,s eTMF platform to increase transparency to enable ...
(Date:9/19/2017)... Inc., a venture-backed medical device company developing a non-invasive, robotically assisted, platform therapy that uses ... today:   ... Jim ... Tom Tefft ... Veteran medical device executive Josh Stopek , PhD, who has led R&D and business ...
(Date:9/12/2017)... and NEW YORK , Sept. 12, 2017   ... for global supply chains, has published the first annual edition of its ... of more than 20,400 companies evaluated by EcoVadis, based on Scorecard Ratings ... 2016. ... CSR Risk & Performance Index ...
Breaking Medicine Technology: