"In a remarkably rapid translation of laboratory research findings into a treatment with the potential to benefit patients UC San Francisco scientists have successfully completed a Phase II clinical trial showing that an FDAapproved antihistamine restores nervous system function in patients with chronic multiple sclerosis MS. In light of previous laboratory studies of the antihistamine compound at UCSF the researchers said the drug most likely exerted its effect by repairing damage MS had inflicted on myelin an insulating membrane that speeds transmission of electrical signals in the nervous system. The drug tested in the trial clemastine fumarate was first identified as a candidate treatment for MS in  by UCSFs Jonah R. Chan PhD Debbie and Andy Rachleff Distinguished Professor of Neurology vice chief of the Division of Neuroinflammation and Glial Biology and senior author of the new study. First approved by the U.S. Food and Drug Administration FDA in  for allergies the drug has been available over the counter in generic form since . The researchers said that the Phase II results published online on  October  in The Lancet are the first in which a drug has been shown to reliably restore any brain function damaged by a neurological disease in human patients. To the best of our knowledge this is the first time a therapy has been able to reverse deficits caused by MS. Its not a cure but its a first step towards restoring brain function to the millions who are affected by this chronic debilitating disease said the trials principal investigator Ari Green MD also Debbie and Andy Rachleff Distinguished Professor of Neurology chief of the Division of Neuroinflammation and Glial Biology and medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center. Chan and Green are codirectors of the UCSF SmallMolecule Program for Remyelination and both are members of the UCSF Weill Institute for Neurosciences. The new results are particularly notable Chan said because patients in the trial had suffered from MS symptoms caused by injury to myelin for years. People thought we were absolutely crazy to launch this trial because they thought that only in newly diagnosed cases could a drug like this be effective  intuitively if myelin damage is new the chance of repair is strong. In the patients in our trial the disease had gone on for years but we still saw strong evidence of repair. MS is an autoimmune neurodegenerative disorder that affects nearly . million people worldwide. The disease strikes when the immune system attacks myelin layers of fatty insulating membrane that surround nerve fibers. Unlike the rubber insulation around wires however myelin helps electrical signals in neurons move faster and more efficiently. As myelin damage continues over the course of the disease neurons progressively lose their ability to reliably transmit electrical signals resulting in progressive loss of vision weakness walking difficulties and problems with coordination and balance. Current MS treatments aim to prevent the immune system from doing further harm but none have been shown to repair damaged myelin. In both his  research and in subsequent studies with a mouse model of MS however Chan and colleagues had demonstrated that clemastine fumarate promotes myelin regeneration and restores neural function promising preclinical results that inspired the new study known as the ReBUILD trial. Because the visual system is often one of the first and most prominent parts of the brain to be affected in MS and because there are wellestablished tools to measure the speed of neural transmission in the areas of the brain devoted to vision the research team used a method known as visual evoked potentials or VEPs to assess clemastines therapeutic effects in the trial. The fivemonth Phase II trial enrolled  patients with relapsing but generally longstanding MS whose VEPs reflected preexisting deficits in neural transmission. The researchers showed flickering patterns on a screen to participants and used electrodes placed over the brains visual areas at the back of the head to gauge how long it took for the flickering signal presented to the eye to generate an electrical response that could be detected by the electrodes. The time from presentation of the pattern to the detection of the VEP is a measurement of how long it took for the signal to travel via nerve fibers from the retina at the back of the eye to the visual areas at the back of the brain. To enhance the power of their study the researchers used a crossover design they divided the patient population in two and gave the drug blinded to both participant and researcher to one group and a placebo to the other for  days then they switched between the two groups giving a placebo to the first group and the drug to the other for the next  days. This flipflop technique gave the researchers the ability to compare patients to themselves  a form of control that increased the statistical power of the study by nearly an order of magnitude Green said. During the periods when each group was taking the drug the neural signal from the eye to the back of the brain was significantly accelerated over the baseline measurements taken before the patients began the study. The effect persisted in the group that had switched to placebo suggesting that durable repair of myelin had been induced by the drug. Although the research team could not directly observe evidence of rebuilding of myelin in trial participants using magnetic resonance imaging MRI Chan and Green said that this reflects a weakness of current MRI techniques as a tool for this purpose rather than evidence that myelin regeneration did not take place. We still dont have imaging methods that have been proven to be able to detect remyelination in humans said Chan. That myelin increases the speed of neural transmission is one of the most wellestablished concepts in neurobiology and combined with the clear evidence from Chans preclinical research showing that clemastine fumarate promotes myelin formation myelin regeneration is the only plausible explanation for the VEP results the authors said. This is the first step in a long process Green said. By no means do we want to suggest that this is a cureall. We want to groundtruth myelination metrics  were designing the crucible thats going to be used to test any future method for detecting remyelination.  The work was funded through generous support from the Rachleff Family. In addition to Green and Chan authors all at UCSF include Jeffrey M Gelfand MD MAS Bruce A Cree MD PhD MAS Carolyn Bevan MD W. John Boscardin PhD Feng Mei PhD Justin Inman Sam Arnow Michael Devereux Aya Abounasr Hiroko Nobuta PhD Alyssa Zhu Matt Friessen PhD Roy Gerona PhD Hans Christian von Bdingen MD PhD Roland G Henry PhD and Stephen L Hauser MD. UC San Francisco UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research graduatelevel education in the life sciences and health professions and excellence in patient care. It includes topranked graduate schools of dentistry medicine nursing and pharmacy a graduate division with nationally renowned programs in basic biomedical translational and population sciences and a preeminent biomedical research enterprise. It also includes UCSF Health which comprises three topranked hospitals UCSF Medical Center and UCSF Benioff Childrens Hospitals in San Francisco and Oakland and other partner and affiliated hospitals and healthcare providers throughout the Bay Area."