In a development that could pave the way for treatment for rare neurological diseases and clues to more common ones, physician-scientists at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, the University Hospital for Einstein, have secured a grant to establish a clinical site for the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT). One of only 25 such federally-funded centers in the country, the Einstein-Montefiore site was created in partnership with Einstein affiliates Beth Israel Medical Center in Manhattan and the North Shore-Long Island Jewish Health System. The NeuroNEXT network and its centers were established with grants from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
Huntington's disease (HD) is characterized by ongoing destruction of specific neurons within the brain. It affects a person's ability to walk, talk, and think - leading to involuntary movement and loss of muscle co-ordination. New research published in BioMed Central's open access journal Molecular Neurodegeneration shows that the RyanR inhibitor Dantrolene is able to reduce the severity of walking and balance problems in a mouse model of HD. Progressive damage to medium spiny neurons (MSN) in the brain of a person with HD is responsible for many of the symptoms and is caused by an inherited recessive mutation in the gene 'Huntingtin'. The mutated version of this protein leads to abnormal release of calcium from stores within the neurons which in turn disrupts the connections between neurons firing and muscle contractions, and eventually kills the neurons.
According to results of the phase 3 MermaiHD trial published Online First in The Lancet Neurology, a unique drug (pridopidine) that stabilizes dopamine signaling in areas of the brain controlling movement and coordination in patients with Huntington's disease (HD), a condition characterized by an imbalance in the signaling chemical dopamine, seems to be well tolerated and merits further investigation. So far, no medication has demonstrated the ability to improve the loss of the ability to move muscles voluntarily. At present, the only medication approved for Huntington's disease is tetrabenazine. However, this drug only treats chorea (an abnormal involuntary movement disorder) and is connected with serious adverse effects. Pridopidine is part of a novel class of medications known as dopidines.
Scientists at the Gladstone Institutes have discovered how a form of the protein linked to Huntington's disease influences the timing and severity of its symptoms, offering new avenues for treating not only this disease, but also a variety of similar conditions. In a paper published in Nature Chemical Biology, the laboratory of Gladstone Senior Investigator Steven Finkbeiner, MD, PhD, singles out one form of a misfolded protein in neurons that best predicts whether the neuron will die. Neuronal death is key to the development of Huntington's symptoms - including erratic behavior, memory loss and involuntary muscle movement. This research underscores the value of the cross-disciplinary work done at Gladstone - a leading and independent biomedical-research organization - while revealing techniques that scientists anywhere can apply to conditions involving misfolded proteins, such as Alzheimer's disease and type 1 diabetes.
Melatonin, best known for its role in sleep regulation, delayed the onset of symptoms and reduced mortality in a mouse model of Huntington's disease, say researchers at the University of Pittsburgh School of Medicine and Harvard Medical School. Their findings, published in the Journal of Neuroscience, show for the first time that certain receptors for the hormone reside in the mitochondria, and that there are fewer of them both in affected mice and human brains. Huntington's disease (HD) is an inherited, lethal disorder of involuntary movement, progressive loss of intellectual function and emotional problems, explained senior investigator Robert M. Friedlander, M.D., chair, Department of Neurological Surgery and UPMC Endowed Professor of neurosurgery and neurobiology. A mutant protein, called huntingtin, kills neurons in the brain's striatum and then the cortex.