HD Lighthouse Contributing Editor's Comment: The evidence for lowered levels of brain derived neurotrophic factor (BDNF) is very clear in both the transgenic mice and in human HD patients. BDNF is important because it helps promote the growth of new brain cells and protects existing cells and its reduction is thought to be a major pathology in Huntington's Disease.

Since BDNF crosses the blood brain barrier, the authors of this study investigated whether levels of BDNF could be measured in the blood and whether they would differ between HD patients and a control group.

They defined onset based on motor signs and excluded those who were taking SSRI antidepressants and other drugs known to raise BDNF levels. They found that the average level of BDNF in blood serum from HD patients was significantly lower than in normal controls. Further, lower levels of BDNF in HD patients were correlated both with higher CAG count and a longer duration of the illness.

The sample was small and the study was not longitudinal so more work will need to be done but it looks like BDNF levels in serum may turn out to be a biomarker for disease progression. It is important for researchers to find and validate biomarkers so that clinical trial time can be reduced and those who have not reached clinical onset as it is currently defined can be included in clinical trials. When treatments become available, biomakers may be used to identify when gene carriers should start taking them.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 29 Jun 2007

Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients.

Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, Squitieri F, Silani V

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive degeneration of neurons in basal ganglia and in brain cortex. Brain-derived neurotrophic factor (BDNF) is a pro-survival factor for striatal neurons. Some evidence implicates a brain BDNF deficiency, related to mutated huntingtin expression, in the selective vulnerability of striatal neurons in HD. We compared BDNF serum levels in 42 patients with HD (range 28-72 years, mean age 51.9 +/- 11.5), and 42 age-matched healthy subjects (range 25-68 years, mean age 48.2 +/- 12.5). We evaluated the potential relationship between BDNF serum levels, CAG repeat number (range 40-54, mean 44.8 +/- 3.4) and duration of illness (range 6-228 months, mean 103.6 +/- 62.1). Serum BDNF levels were significantly lower in patients than in age-matched healthy subjects. Lower BDNF levels were associated with a longer CAG repeat length and a longer duration of illness. Severity of the illness, as assessed by the Unified Huntington's Disease Rating Scale (UHDRS) motor and cognitive scores, was negatively related to serum BDNF levels. These results in vivo confirm that the huntingtin mutation causes BDNF production to decline and show that the BDNF deficiency is detectable in HD patients' sera. Further studies on a larger sample size should confirm whether BDNF concentrations in patients' serum could be a useful clinical marker related to the patients' disease phenotype. (c) 2007 Wiley-Liss, Inc. # # #

Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2007 Jun 5;144(4):574-7

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