Huntington’s disease is a neurological disorder that affects more than 30,000 people in the United States. The disease is caused by a single abnormal huntingtin gene. Instead of producing a functioning protein as the normal gene does, the abnormal gene produces a misformed protein with excess amounts of the amino acid glutamine. This glutamine-rich region causes the misformed protein to sticks to other proteins and causes degeneration of nerve cells in the brain. The disease is familial, passed from parent to child. Only one copy of the defective gene is necessary to produce the disease. This means that there is a fifty percent chance that a child may be born with the disease if only one parent carries a single defective gene. Huntington’s disease was discovered in 1872 after a case study of Long Island families with movement disorders. George Huntington was the first to identify Huntington’s disease as a genetic disorder and subsequently described the cognitive and physical symptoms of the disease.

The earliest symptoms, which first appear in middle-age, include personality changes, such as mood swings, irritability, depression and emotional disturbances, as well as impairments to cognitive functions. The disease makes it difficult to make judgments and decisions, remember facts or learn new information. As the disease progresses, vital functions begin to slow, affecting balance, eating, swallowing and speech. Additionally, jerking, uncontrollable movements of the body are common. Signs and symptoms of Huntington’s disease continue progressively until death, which usually occurs 10-30 years after the first symptoms appear. Infections, falls or other complications of the disease frequently result in death.

Currently, treatments are not available to stop or reverse the course of Huntington’s disease. However, medicines can be used to help manage some of the emotional and physical symptoms. The physical and emotional symptoms associated with the disease can also be helped by physical therapy, occupational therapy and speech therapy.

Suggested Reading: Huntington's Disease

Major advancements have been made in Huntington’s disease research since the huntingtin gene was first discovered in 1993, prompting a dramatic increase in Huntington’s disease research. In 1996, the first transgenic Huntington’s disease mouse model was used for research, and today there are various mouse models that are used in research to expand knowledge about the disease. The mouse models, along with new technologies, have made it possible to further identify possible drugs and supplements for treatments. As of mid-2008, there are more than two dozen investigational therapies for Huntington’s disease in development: four therapies are in Phase 3; five therapies are in Phase 2; one therapy is in Phase 1; eleven therapies are in preclinical trials; and four therapies are in basic research. They include nutritional supplement therapies, dopamine blockers or stabilizers, glutamate blockers or stabilizers, brain derived neurotrophic factors antioxidants, genetic approaches and restorative technologies. Other research includes a combination of cancer drugs and AIDS drugs to treat Huntington’s disease.

A federal law passed in 1982 called the Orphan Drug Act grants special status to compounds that are tested to treat rare diseases or conditions. Many potential treatments for the symptoms of Huntington’s disease have been designated Orphan Drug status. For example, Rilutek, primarily used for the treatment of Amyotrophic Lateral Sclerosis (ALS) that has symptoms similar to that of Huntington’s, was designated an orphan drug in October of 1996. Other potential treatments with Orphan Drug status include:

• • Cysteamine in May 2008 (FDA approved for cystinosis)
• • Tetrabenazine in December 2007 (Only drug approved by FDA for HD in Aug 2008)
• • Clotrimazole in March 2006 (FDA approved for treatment of fungal diseases)
• • 4-(3-Methanesulfonyl-phenyl)-1-propylpiperidine HCl in December of 2005 (not evaluated by FDA)
• • Creatine in October 2005 (dietary supplement, not evaluated by FDA)
• • Ubiquinol in April 2004 (dietary supplement, achieved new dietary ingredient (NDI) status with the FDA in 2005)
• • Coenzyme Q10 in March 2001 (dietary supplement, not evaluated by FDA)
• • Ethyl Eicosapentaenoate in April 2000 (dietary supplement, now in Phase 3 clinical trials for HD by Amarin)
• • Remacemide in March 2000 (non-FDA approved drug)

Although these treatments all have Orphan Drug status they are mostly still in experimental stages. Only one drug has been approved by the FDA for Huntington’s disease. Tetrabenazine, which became an Orphan Drug in December 2007, was approved by the FDA in August 2008 to treat the abnormal involuntary movements (called chorea) associated with Huntington’s disease.

Many organizations are dedicated to advancing the field of Huntington’s disease research and drug development. Among these are:

• • CHDI Foundation, Inc., a leading non-profit organization supporting an international network of research laboratories from academia and industry to pursue novel ways to treat Huntington’s disease.
• • Huntington’s Disease Society of America, a national, voluntary health organization dedicated to improving the lives of people with Huntington's disease and their families.
• • The Hereditary Disease Foundation, which sponsors workshops, grants and targeted research contracts to develop new treatments and cures.
• • The Huntington Project, which brings together the entire clinical research community to engage in the decision-making process required in developing treatments for Huntington’s disease.

Vertex entered into a collaboration with CHDI in June 2008, aimed at developing assays for use in discovering novel compounds that may benefit individuals with Huntington's disease. The collaboration is focused on two main areas:

• 1. Errant protein folding and aggregation, a key cellular disruption that is believed to play a role in Huntington’s disease
• 2. Neurogenesis, a process that when disrupted, can result in Huntington’s disease-related cognitive and physical impairments
  

Protein misfolding may contribute to several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS, often referred to as "Lou Gehrig's Disease"). The information gained from this collaboration may provide insight into new approaches for treating Alzheimer’s disease, Parkinson’s disease and ALS. See Vertex’s press release for more information.