Wise Young
08-29-2005, 10:24 PM
BDNF is brain-derived neurotrophic factor, one of the main brain neurotrophins. The authors treated 10 ALS patients with intrathecal (into the CSF surrounding the sinal cord) BDNF for 9 months, compared against another 10 patients that received intrathecal placebo. The drug apparently made autonomic nervous function worse, associated with increased norepinephrine levels. This is of interest not only from the viewpoint of ALS but also BDNF is one of the neurotrophins that has been proposed to be part of a combination therapy for spinal cord injury. This would tend to argue against its use.
Beck M, Flachenecker P, Magnus T, Giess R, Reiners K, Toyka KV and Naumann M (2005). Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF. Amyotroph Lateral Scler Other Motor Neuron Disord 6: 100-3. This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect. Department of Neurology, ALS Study Group, Julius-Maximilians-University Wuerzburg, Germany. marcus.beck@mail.uni-wuerzburg.de http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16036433
Beck M, Flachenecker P, Magnus T, Giess R, Reiners K, Toyka KV and Naumann M (2005). Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF. Amyotroph Lateral Scler Other Motor Neuron Disord 6: 100-3. This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect. Department of Neurology, ALS Study Group, Julius-Maximilians-University Wuerzburg, Germany. marcus.beck@mail.uni-wuerzburg.de http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16036433