Researchers from the Medical Research Council (MRC) London Institute of Medical Sciences report that based on a recent study powered by advanced scanning technology, they are able to associate lower levels of a protein in connection with neurons in schizophrenia patients. Could it be that these changes underlie the cognitive difficulties seen in schizophrenia and, hence, open up new drug development targets?
Back in the early 1980s, researchers hypothesized that what actually caused schizophrenia was dysfunctional synapses—where the nerve signals are transmitted between neurons in the brain. In the past, the study of this subject was in post-mortem brain samples, or animal and cell models in the lab.
But for this study recently published in Nature Communications, the UK-based team identified this pattern in living brains for the first time. By utilizing a tracer that emits a signal that can be tracked by a PET brain scan, the team could study 18 adult schizophrenia patients and compare them to 18 adults without the condition. Once the patients were injected, the tracer binds specifically to a protein found in synapses known as SV2A (synaptic vesicle glycoprotein 2A), which is considered a good marker of the density of synaptic nerve endings in the brain.
During the study, those individuals with schizophrenia all received antipsychotic medication; the researchers sought to exclude this as a factor in the synaptic dysfunction. Additionally, Haloperidol and olanzapine were administered to rats for 28 days and observed that it had no effect on levels of the protein SV2A.
The investigators found that in the schizophrenia patients, levels of the synaptic protein SV2A were in fact lower in the front parts of the brain—as noted in the sponsor’s press release, this is the area of the brain needed for planning. This finding has considerable implications when thinking about how to help those with schizophrenia in the future. After all, study lead Professor Oliver Howes reminded all of those with interest that the only treatments for schizophrenia today deal with psychotic symptoms but not at all with the condition’s “debilitating cognitive symptoms such as loss of ability to plan and remember” and commented that this, in fact, has far greater damage long term. Could it be that synaptic loss underlies these symptoms?
A Special Research Center
The MRC London Institute of Medical Sciences “is one of a few places in the world with this new tracer.” Hence, their team is taking a global leading position is uncovering the correlation between lower levels of synaptic protein and the development of schizophrenia. The team in London could be one of the first to identify SV2A as a target for new therapies.
Under the current leadership of Professor Amanda Fisher, MRC London Institute of Medical Sciences is at the forefront of innovative biomedical research and in partnership with Imperial College London and others, promoting the translation of research for maximal benefit. The center was established in 1998 as a research institute of the Medical Research Council and works closely with Imperial College London and its Hammersmith Hospital Campus.
Call to Action: For those interested, keep an eye on this MRC-based team. Next, they hope to create a study where they can scan a more youthful study group experiencing earlier stages of the condition with the goal of understanding how synaptic levels may change during the development of the condition.