New treatment could reverse paralysis
the paralysis that can occur after spinal cord injuries, which
occur in around 11,000 people in Europe every year.
Scientists at the Deutsches Krebsforschungszentrum (German Cancer Research Center, Heidelberg) have shown in animal studies that paralysis caused by spine injury can be reversed by blocking apoptosis - also known as programmed cell death - a process which contributes to much of the damage that occurs when nerves are severed.
One of the authors of the study, Dr Ana Martin-Villalba of the Immunogenetics Division at the DKFZ, told DrugResearcher.com that by interrupting the apoptotic signal using monoclonal antibodies, it may be possible to give injured nerves time to recover and reform connections, eventually allowing recovery of movement.
The researchers report in Nature Medicine (April issue) that the antibodies, raised against a protein called CD95 L, can block the cellular cascade that lead to apoptosis, but also helped mice with spinal cord injuries to recover a range of motor functions, including the ability to walk, swim and navigate across a horizontal ladder-like grid with irregular gaps.
In addition, tissue sections of the treated animals revealed newly growing nerve fibers beyond the place of injury. Treatment with antibodies also prevented oligodendrocytes - cells that insulate the cord-like nerve fibers and thus facilitate signal transmission - from dying.
The mice received an intra-peritoneal injection of the antibody, which blocks CD95 L from binding to its receptor (CD95) on nerve cells. Dr Martin-Villalba said that a similar approach could easily be used to treat humans, perhaps delivered by paramedics at the scene of an accident.
Indeed, a biotechnology company based in Heidelberg in Germany has produced a humanised antibody fragment targetting CD95, and is planning to enter it into clinical studies in the first quarter of 2005.
Dr Martin-Villalba also noted that inhibiting apoptosis in nerve cells could also be used to limit the damage in the brain that can occur after a stroke, traumatic brain injury or neurodegenerative diseases such as Parkinson's and Alzheimer's. As with spinal cord injury, the initial damage caused by a stroke is followed by a cascade of events in which neighbouring cells are go into programmed cell death, with the damage radiating out from the initial lesion over time.
Her team published a report in 2001 showing that this approach could limit the size of an infarct lesion after a stroke in mice, and also reduced the death rate and improved the clinical outcome of the animals.One issue that clearly needs to be established is the safety of blocking CD95. As inhibiting blocks programmed cell death - and this is an important control mechanism protecting against the development of cancer in the body - their may be a toxicity concern.
However, Dr Martin-Villalba noted that with an acute treatment protocol such as the one used for treating spinal trauma this would be unlikely.
