Huntington's Disease Lighthouse Families

Here's another major article that adds to our information about autophagy.

Dr. Steven Hersch and colleagues have investigated the effect of the rapamycin derivative, everolimus, on the R6/2 mice.  While there was improvement in rotarod performance and the drug did penetrate the brain, it failed to protect neurons.  Everolimus reduced the HD protein in skeletal muscle tissue but not in the brain where it did not activate autophagy.

Neurosearch has announced the results of its Phase IIB clinical trial of its dopamine stabilizer, Huntexil, originally named ACR16 when it was in preclinical development. 

A lot of good research is coming from the Buck Institute.  Dr. Lisa Ellerby, Dr. Robert Hughes, and colleagues at the Buck Institute for Age Research have identified a group of proteinases as promising new targets for treatment. Proteinases are enzymes which cleave proteins.

The approach was based on the toxic fragment hypothesis that has received much support in previous research studies.  The idea is that a key event in the development of Huntington's Disease is the cleavage of the HD protein into fragments which then enter the nucleus of the cell and cause damage.

Because HD is associated with oxidative stress, some Lighthouse readers are taking antioxidants.  A study at the University of Cambridge raises the issue of whether this is a good strategy since some antioxidants seem to interfere with autophagy.  However, other studies have suggested that autophagy is already impaired in HD ( see: cargo recognition is impaired in HD ).

The attendees were welcomed by Louise Vetter who urged people to answer thequestionnaire from Project Aware which was available in the exhibition hall oncomputers and on paper. Without clinical trials, we will not have treatments andresearchers need to know why potential participants choose to participate or not.

This session was moderated by Dr. Steven Finkbeiner. The first speakers were Dr. Joachim Tedroff, chief medical officer, and Asa Rembrandt, project manager for ACR-16. The dopamine stabilizer ACR-16 now has a generic name pridopidine and a trade name of Huntexil. There are ten studies ongoing or planned for this drug.

Robert Ferrante, Steven Hersch, and colleagues have identified a potential biomarker for Huntington's Disease progression that can be measured in blood samples.   An isoenzyme of creatine kinase, CK-BB, was shown to be reduced in the blood and brains of two mouse models over time.   What is exciting is that CK-BB was also found to be reduced in the blood of pre-manifest gene carriers, and reduced even more in symptomatic patients.  

Collaborators from the University of California at Irvine, Massaschusetts General Institute for Neurodegenerative Disease, the Brain Mind Institute in Switzerland and other labs have shown that SIRT2 inhibition is helpful in invertebrate and striatal neuron models of Huntington's Disease.

The press release below involves a correction to previously announced results of the Huntexil (ACR16) clinical trial in Europe.

Autophagy increases but is impaired, leading to an increase of the HD protein in the cytosol.