Researchers in California may have discovered new drug targets to treat an incurable hereditary disease that leads to loss of motor coordination, dementia and death. The Buck Institute for Age Research announced that it had identified a family of enzymes involved in the processes that cause Huntington’s disease.
Huntington’s disease is caused by a mutation on a certain gene, called the huntingtin gene, that causes abnormalities in the huntingin protein. The progression of Huntington’s disease accelerates when the protein is cut into smaller, toxic fragments by molecular activity. Buck Institute researchers identified 11 proteases, or enzymes, that reduced the accumulation of toxic protein fragments associated with Huntington’s disease. (Scientists in Australia were recently able to observe the accumulation process up close.)
Four of the proteases belong to a class of enzymes known as matrix metalloproteinases (MMPs). MMPs are currently a drug development target to treat various cancers. They have also been linked to stroke and inflammation. The big challenge will be figuring out how to inhibit only the MMPs associated with Huntington’s and not others. Researchers will also have to find a way to make the drug cross the blood-brain barrier.
Huntington’s disease causes nerve cells in the brain to degenerate. The disease affects an estimated 5 to 10 out of every 100,000 people. Symptoms usually appear between the ages of 30 and 50, although the disease sometimes develops during childhood. Patients gradually lose their ability to speak, move and think clearly. Dementia and emotional disturbance may occur. Eventually, patients may become unable to perform even simple tasks such as feeding themselves or swallowing. Although medicine can alleviate some of the symptoms, there is no way to stop the progression of the disease.
Some of the companies working to treat Huntington’s disease include Medivation, which is developing a treatment for the cognitive impairment associated with Huntington’s; ENKAM Pharmaceuticals, currently screening drug development candidates; Prana Biotechnology, an Australian company focused on neurological diseases; well-known Vertex Pharmaceuticals, and French pharmaceutical company Trophos.