Managed Care - November 2008 - (Page 46)

TOMORROW’S MEDICINE Gene Therapy Offers HD Patients Relief From Some Symptoms Tetrabenazine inhibits the transport of a molecule called vesicular monoamine transporter type 2 or VMAT2 Thomas Morrow, MD H untington’s disease (HD), named for George Huntington, MD, who lived from 1850 until 1916, is a neurodegenerative disease. It is an autosomal dominant disease and results from a defect of the Huntingtin gene located on chromosome 4, which codes for the Huntingtin protein. (Yes, the disease name is spelled differently from the gene and protein.) The disease causes a variety of symptoms but the most characteristic symptom is chorea — random, jerky, involuntary, and uncontrollable movements which initially manifest themselves as an unsteady gait, a general lack of coordination, and slurring of speech. As the disease progresses, it affects virtually all muscular dependent functions and leads to incomprehensible speech, difficulties chewing and swallowing, and abnormal facial features. Accompanying the chorea are cognitive and psychiatric symptoms. The cognitive abilities most affected are the functions such as planning, cognitive flexibility, perception, abstract thinking, and memory impairments. Psychiatric symptoms may include depression, anxiety, aggression, compulsive behavior, and a variety of addictions including alcoholism, hypersexuality, and gambling. Huntingtin protein A normal Huntingtin gene contains a repeating series of the three nucleic acids, CAG, on one end. The trinucleotide CAG codes for the amino acid glutamine. Each additional trinucleotide CAG results in an additional glutamine being placed on the protein. A normal gene can have up to 27 glutamine Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 23 years of managed care experience at the payer or health plan level. amino acids on its end. This chain is referred to as polyglutamine or polyQ. Having more than 27 glutamine amino acids in a row is abnormal but patients do not appear to become symptomatic until the chain reaches 36 glutamines in a row, which causes symptoms in some people but not in others. With a chain of 40 or more, people exhibit the disease. As the number of repeats increases, the rate of progression to disease increases and the age of onset becomes earlier. However, the relationship between the length of the polyQ and age of onset is not linear or absolutely predictable. The Huntingtin protein is necessary for development and survival, but the presence of a long chain of polyQ results in the inability of brain cells to metabolize and degrade this protein completely. This causes an accumulation of protein fragments. These protein fragments are thought to interfere with a number of cellular functions and eventually cause cell death. Cell death occurs primarily in the striatum of the brain, an area critical for muscular control signals. Other areas affected are the cortical areas of the frontal and temporal lobes. In the past, HD was typically diagnosed in the second or third decade of life for those with a high polyQ and in the fourth or fifth decade for the more moderate lengths of polyQ. The disease causes continued deterioration for an additional 15 to 20 years until death. A pathological diagnosis is established by a neurological exam or evidence of cell loss in the areas of the brain listed above as seen by CT or MRI. Genetic testing can determine the number of CAG repeats. This test is not to be taken lightly. It must be accompanied by significant counseling, as there is no cure for HD. Currently there are symptomatic therapies that are used off-label to control the emotional and psychiatric components of the disease. In 46 MANAGED CARE / NOVEMBER 2008

Table of Contents Feed for the Digital Edition of Managed Care - November 2008

Managed Care - November 2008 Editor’s Memo Contents News and Commentary Legislation & Regulation Letters Medication Management Compensation Monitor Do It Yourself for Less Biomarkers Promise, but Do They Deliver? Oncologists Complain About Drug Payment Consider Blood Pressure Self-Monitoring Q&A: Keep Industry in the Game Formulary Files Plan Watch Tomorrow’s Medicine Outlook Respiratory Syncytial Virus Managed Care Considerations Contents Continuing Education Objectives RSV Disease in the Pediatric Population In the Trenches RSV Infection in the Adult Population Health Plan Medical Director Health Plan Pharmacy Director RSV Issues and Solutions Assessment/Evaluation/Certificate Request Post-Test

Managed Care - November 2008

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