By Eva Briggs, MD
I first heard of Huntington’s disease when I read a biography of Woody Guthrie, the famous folk singer who died from this disease.
Years later I cared for a young man with the rare juvenile onset form. He was already severely limited by Huntington’s disease in his late 20s. A decade after that, a young woman told me that her mother, a woman with whom I’d had a friendly relationship, had been diagnosed with Huntington’s. Until now there has been no treatment to slow or cure this disease. But a recent study of a new gene therapy provides hope that there may be an effective treatment on the horizon.
Huntington’s disease is a degenerative neurologic disease caused by an abnormal gene. Most cases are inherited from an affected parent. Our genes come in pairs and only one defective gene is needed to cause Huntington’s disease. So, a parent with the faulty gene has a 50% chance of passing that on to each child. In the US it’s estimated that 4 in 5 people per 100,000 have this disease.
Symptoms usually start when patients are between 30 and 50 years old. By the time someone becomes symptomatic, they often have already had children and perhaps passed the gene on. The abnormal gene is located on chromosome 4. This gene codes for a protein called huntingtin. The function of normal huntingtin remains unknown. This gene has repeating segments of the nucleotides C-A-G (cytosine, adenine and guanine, three of the building blocks of DNA). C-A-G tells the cell to make the amino acid glutamine. The patient then produces a mutant huntingtin with added strings of glutamine. An unaffected person has between 10 and 35 repeats of C-A-G. If someone has 36 or more repeats, they develop Huntington’s disease. The rare person with 50 or more repeats develops juvenile Huntington’s disease with the onset by age 20.
Huntingtin accumulates in the brain, eventually damaging nerve cells. Symptoms can be motor (movement), cognition (thinking) and psychiatric. Huntington’s disease patients develop chorea, uncontrolled jerky movements. In later stages, their muscles may become stiff and rigid. As thinking deteriorates, patients have trouble with daily tasks and trouble learning new information. Memory is impaired and patients lose the ability to make important decisions. Psychiatric symptoms include apathy, irritability, impulsivity, and obsessionally. Associated psychiatric diagnoses could include depression, mania, OCD and psychosis.
After symptoms start, affected individuals can live another 10-30 years. Currently there is no specific treatment. Medications can help some symptoms, but they don’t slow, reverse or cure the disease.
A recent study, however, showed promising results for gene therapy. The treatment is called AMT-130. It uses a viral shell to deliver tiny bits of mRNA to the brain cells affected by accumulation of huntingtin. The mRNA interferes with the cell’s ability to manufacture the abnormal huntingtin protein. This slows its buildup in the brain. In this study AMT-130 slowed disease progression by 75%. For example, after four years patients’ symptoms worsened only by the amount typically occurring in one year.
A big downside is that this medicine has to be delivered by catheter directly into the brain during an eight–12-hour brain surgery. This first study only included 24 patients. Some patients developed headache and swelling after treatment. These symptoms resolved in all affected patients and were felt to be related to the surgery. So far, no other adverse effects were noted.
This treatment is still in the early experimental phase. It is not generally available. But it gives hope that perhaps it will lead to a more widely available treatment. And it’s not yet known whether delivering AMT-130 to a person with the defective gene before symptoms develop will delay or prevent the disease.
Eva Briggs is a retired medical doctor who practiced in Central New York for several decades. She lives in Marcellus.