Susan Jeffrey

June 22, 2007

June 22, 2007 (Istanbul) — A new study shows a relationship between the Huntington's disease (HD) mutation and reduced levels of brain-derived neurotrophic factor (BDNF) in the sera of patients, suggesting it may provide a useful clinical biomarker in the disease.

The study was presented here at the 11th International Congress of Parkinson's Disease and Movement Disorders and was recently published in the June 5 issue of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.

Jenny Sassone, PhD, and Andrea Ciammola, MD, from the Dino Ferrari Center, IRCCS Instituto Auxologico Italiano, in Milan, Italy, told Medscape that the work presented here shows that BDNF levels were significantly correlated with the duration and severity of disease as well as size of the HD mutation in these patients.

"Our study suggests that HD mutation causes BDNF production to decline," Dr. Sassone said. "The low BDNF levels can be detected in the serum of these patients and may possibly be a biomarker for HD progression."

Dr. Ciammola pointed out that this series was only 42 patients and more work in a more extensive group is needed. However, he noted, "We now have in our lab more than 100 patients, and the data confirm these preliminary data, so I think we are able to use this as a biomarker."

Prosurvival Factor

In HD, motor, cognitive, and psychiatric symptoms are accompanied by progressive deterioration of neurons in the basal ganglia and brain cortex, the researchers note. BDNF is a trophic factor produced in the cortex. From there it is transported to the striatum, where it acts as a prosurvival factor for striatal neurons and has been shown to be necessary for the survival of these neurons, Dr. Sasonne noted.

"Since previous reports showed that BDNF levels are decreased in the brain of HD patients and also in brains from HD mice, we compared serum BDNF levels between HD and control patients," she said.

Levels were compared in 42 HD patients with an age range of 28 to 72 years (mean, 51.9 years) with 42 age-matched healthy controls ranging in age from 25 to 68 years (mean, 48.2 years). They evaluated the relationship in these subjects between serum levels of BDNF and CAG repeat number and duration of illness. CAG repeats ranged from 40 to 54, with a mean of 44.8, and illness ranged from 6 to 228 months, with a mean of 103.6 months.

They found that serum BDNF levels were significantly lower in patients than in healthy controls.

"Next, we assessed whether there was a correlation with clinical and genetic variables of HD patients," Dr. Sassone said. They found that lower BDNF levels were significantly associated with longer CAG repeat length and a longer duration of illness.

Further, severity of the illness, as assessed by the United Huntington's Disease Rating Scale (UHDRS) motor and cognitive scores, was negatively related to serum BDNF levels.

In this paper, they also included preliminary data on 7 HD patients who were as yet presymptomatic and found values that were intermediate between normal controls and symptomatic subjects, Dr. Ciammola said. "There is a constant decrease of BDNF between normal control subjects and symptomatic subjects," he said. It's possible, then, that if therapies are found to address the disease, their effects might be assessed using BDNF levels, he speculated.

"Although BDNF changes could be present in other neurodegenerative disorders characterized by cognitive and motor impairment, the significant correlation of serum BDNF with HD duration and mutation size strongly suggests that the BDNF variability in peripheral HD tissues could be a useful in vivo biomarker," they conclude.

The study was funded by a grant from Telethon–Italy.

11th International Congress of Parkinson's Disease and Movement Disorders: Poster 103. Presented June 5, 2007.

Am J Med Genet B Neuropsychiatr Genet. 2007;144B:574-577.

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