Basic Research

Zinc Finger Technology: Another Way to Silence the HD Gene

A team of researchers from Barcelona, Spain, led by Dr. Mark Isalan and Dr. Mireia Garraga-Canut, have developed artificial zinc finger protein strands which bind the longer CAG repeat stretches of the HD protein while leaving the normal huntingtin protein gene, neighboring genes, and other genes with CAG repeat stretches unaffected.  They achieved a 60 percent reduction of the HD protein in a mouse model and improved symptoms.

Grape Derived Polyphenols

Researchers at the Mount Sinai School of Medicine in New York have investigated grape derived polyphenol extract (GDPE) as a potential treatment for Huntington's disease. They found promising results in a cell model, a drosophila model, and the R6/2 mice.

In previous studies, the authors investigated the bioavailability of GDPE and found that although it is metabolized in the gut, it does cross the blood brain barrier and can be detected in the brain.

DRP1 is Identified as a Promising Therapeutic Target

Impaired energy metabolism has been shown to be a major pathology in  Huntington's disease.  The mitochondria, the cell's energy factories,  have not been found to be  intrinsically defective but are thought to be  mismanaged in some way.  A University of Central Florida research team  lead by Dr.

A New Drug Enhances Neural Growth Factor

In the press release below, CeNeRx BioPharma, Inc. announces that their new drug CXB909 will go into clinical trials for peripheral neuropathy.  This is of interest to the HD community since the drug enhances the effects of neural growth factor (NGF) and may be neuroprotective in Huntington's Disease.  Preclinical studies of the effects on this drug on neurodegeneration have been done but do not appear to have been published so I do not know which disease models were used.  Still, the Lighthouse will follow this company's efforts.

Novel Benzoxazine Compounds

Researchers from Southern Methodist University and the University of Texas at Dallas have collaborated to develop new benzoxazine compounds to prevent neurodegeneration. Similar indolone compounds had been found to inhibit cell death but were toxic at higher concentrations. The benzoxazine compounds were synthesized by altering the ring core structure, preventing toxicity even at high doses. Benzoxazines are the reaction products of an amine, a phenol and formaldehyde.

Everolimus Not Neuroprotective in the R6/2 mice

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.

Metalloproteinases

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.

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