Treatment for Fragile X could target this protein

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A simple blood test can detect Fragile X syndrome, the most common cause of autism, but there’s no treatment or cure.

Now, scientists have identified a protein that appears to be the culprit in causing many behavioral symptoms as well as molecular and cellular abnormalities related to the condition.

“We began with 600-800 potential protein targets, searching for the equivalent of a needle in a haystack,” says Hongbing Wang, a physiologist at Michigan State University. “Our needle turned out to be ADCY1. When we compared levels of this protein in Fragile X mouse model to normal controls, we saw a 20-25 percent increase of ADCY1.”

Subsequent tests of the team’s prime-target protein on the Fragile X mouse model revealed four key results:

  1. Reducing the expression of ADCY1 eliminates many autism-like behaviors.
  2. The protein’s increased expression causes increased signaling in neurons.
  3. Reducing levels of ADCY1 dampens neuron signaling to levels within a normal range.
  4. Neurons associated with Fragile X have excessive dendritic spines, or bumps, when compared to those in healthy patients. Reducing the rampant protein also improves the appearance of the neurons.

Finding a single target that’s responsible for so many of the causes makes the research attractive to pharmaceutical companies, Wang says.

How to reduce subtle symptoms of fragile X

“Our research has identified a key target and a new approach that could easily be pursued by pharmaceutical companies. We’ve shown an accessible target that, through treatment using NB001, suppresses activity. The next steps would be to test toxicity and optimization.”

NB001, an experimental compound that also holds potential as a painkiller, delivers positive preliminary toxicity tests as well as demonstrated the ability to pass the blood brain barrier, the protective membrane separating the bloodstream from brain extracellular fluid.

Although the study, published in Nature Communications, reveals a critical target and potential medicine, the findings are still years away from being considered for human clinical trials, Wang says.

In addition to potential drug development for adults, future studies could focus on children. Since the team studied adult mice, the question of catching the problem at an earlier age has yet to be addressed. Scientists wonder if catching the disease at an early stage, by a blood test for example, could stop it before symptoms surface.

Additional researchers from Michigan State and from Emory University are coauthors of the paper. The National Institutes of Health and FRAXA Research Foundation funded the work.

Source: Michigan State University