Like all scientific endeavors, Huntington’s disease has moments of promise and moments of disappointment.

 

A major disappointment came on April 24, 2007 with the news that the Amarin Corporation’s drug Miraxion failed to bring improvement in the symptoms of hundreds of patients undergoing a six-month phase III (final stage) clinical trial in the U.S. and six European countries.

 

The HD community had long awaited the results of this trial with great anticipation, because earlier tests seemed to indicate that Miraxion might slow cell death and have anti-inflammatory effects on the brain. Originally known as LAX-101, Miraxion is produced from fish oil and contains the omega-3 fatty acid ethyl-EPA, or eicosapentaenoic acid.

 

Although safe and well-tolerated, in the most recent clinical trial Miraxion failed to improve movement, cognition, and functional capacity in the HD patients.

 

Miraxion had received fast track status from the U.S. Food and Drug Administration (FDA) and is considered an orphan drug in both the U.S. and Europe. Amarin had expected to launch the drug into the market very soon after the phase III trial.

 

Amarin and scientists will continue to analyze the results of the trial to try to understand its ineffectiveness for HD.

 

Miraxion did not yield “results that we were hoping for,” HDSA CEO and Executive Director Barbara Boyle stated. “Representatives of Amarin plan on attending the HDSA National Convention in June [in Oklahoma City], to offer more information and answer questions about these studies, and future work…. HDSA is committed to our research program and will continue to push Amarin, and our other corporate partners in their pursuit of treatments for Huntington’s disease.”

 

Amarin collaborated in the trial with the Huntington’s Study Group (HSG), an HDSA-backed research initiative.

 

“We remain committed to investigating experimental treatments that will make a difference in the lives of those affected by Huntington disease,” said Dr. Ira Shoulson, the lead HSG investigator in the trial.

 

Bernhard Landwehrmeyer, the lead European investigator, said, “The two studies combined enrolled the largest number of patients with Huntington’s disease in any Huntington’s disease therapeutic trial to date and provided clear and unequivocal answers, although not the answers we hoped for.”

 

In science, however, negative clinical results can still have positive significance because they show the direction in which researchers should not advance. The conclusions about Miraxion will allow HD clinical researchers to focus their energies on other, potentially more promising medications.

 

In fact, new understanding of the disease and potential agents continues at a brisk pace.
 

Key enzyme 

At practically the same moment that Amarin reported its results, other scientists announced that they had discovered how a key enzyme in cells actually caused the harmful DNA sequences of Huntington’s disease to worsen. They are already screening for molecules that could alter the effects of the enzyme.

 

Research sponsored by the Buck Institute, which focuses on extending the healthy years of an individual’s life, has identified 234 new proteins that bind to normal and mutant forms of huntingtin, the protein that causes HD. The work, which involved high-tech screening of the human genome and proteome, was unprecedented both in terms of its scale and in the way the protein interactions were validated in a genetic model of the disease. By conducting additional experiments in fruit flies genetically altered to express features of human HD, scientists showed that changing the expression of these interacting proteins affected the degree of damage seen in the fly neurons. This indicates that a significant number of the proteins might be potential drug targets for HD. The new genes and proteins discovered in this study are being screened and analyzed in cultured mammalian cells; the ones that show activity in ongoing experiments will be tested in mouse models of HD. Results of the study, which may facilitate the discovery of an effective treatment for HD, were published in the May 11 edition of PLoS Genetics, an online, open-source journal, enabling scientists from around the world to take advantage of the findings immediately.

 

The Avicena Group, a California-based biotech firm, will soon launch a clinical trial for its drug HD-02, which contains creatine, a dietary supplement taken by many people in the HD community after positive results for the substance were produced in mice.

 

Canadian researchers are very close to defining drugs that could redirect the huntingtin protein from accumulating in the wrong place within brain cells.

 

CHDI (Cure Huntington’s Disease Initiative), the pharmaceutical startup backed by HDSA and other organizations, will be testing KW-6002, an adenosine receptor antagonist for possible use in a clinical trial.

 

Curcumin (the spicy ingredient in curry and other foods) has shown increasing promise as a possible agent for treating HD.

 

Researchers will also be looking at ways to reduce the brain’s level of copper, which HD patients have in excess.

$13 million for San Diego researchers
 

Meanwhile, stem cell research continues to forge ahead in San Diego, where nineteen scientists will receive $13.37 million for various projects under California’s $3 billion stem cell program. Earlier in the year scientists at the Burnham Institute for Medical Research in La Jolla demonstrated the use of human embryonic stem cells in the treatment of mice with Tay-Sachs disease, which, like HD, is a degenerative brain disorder.

 

Dr. Steve Stice, a researcher at the University of Georgia, has discovered a way to produce billions of stem cells. He intends to distribute these cells to biological labs and companies throughout the world to accelerate research on neurological diseases.

 

In March the Sony Corporation announced that its PlayStation 3 video game consoles would be enhanced to join a supercomputing network researching causes of cancer, Alzheimer’s, Huntington’s, and other diseases caused by so-called “misfolded” proteins. The game’s console software will permit users to click on an icon on their TV screens to have their machines devote computing power to medical research whenever the device is idle.

 

Battling boredom and keeping life colorful might help dementia patients with memory difficulties, according to another new study. Companionship is also important.

 

The urgency of finding treatments for neurological diseases is growing. Cases of Alzheimer’s disease alone grew ten percent in the last five years, to more than five million individuals.

 

In March the Hereditary Disease Foundation issued a summary of its 2006 research meeting, attended by more than 300 scientists from around the world. The foundation reported that HD continues to present puzzles and surprises, but that increased knowledge and a growing array of potential treatment strategies are causing researchers to make great strides towards making HD a treatable and curable disease.