Health
Treatment reverses the paralysis of the mouse. Provides a general delivery platform for neuropharmaceuticals–ScienceDaily
Although rare, botulism can cause paralysis and is potentially fatal. This is caused by the nerve-damaging toxin produced by Clostridium botulinum. It is the most powerful toxin known. These toxins are common in contaminated foods (mainly due to home canning). Infants can also develop Clostridium botulinum poisoning by ingesting Clostridium botulinum spores in honey, soil, or dust. The bacteria then colonize the intestines and produce toxins.
When paralysis occurs, there is no way to get rid of it except by waiting for the toxins to disappear. People with severe cases of botulism may need to be ventilated for weeks or months.However, the new therapeutic approaches and delivery methods described today Scientific translation medicine, You can change it.
“There are antitoxins, but they only work before the toxins enter the motor neurons,” said Dr. Mindon, a urologist at Boston Children’s Hospital and the corresponding author of the treatise. “We have developed the first treatment that can eliminate the toxin after it gets inside the neuron.”
If proven in humans, this approach would represent a breakthrough in the treatment of botulism. In mice, the treatment successfully entered the neurons, reversing muscle paralysis within hours and allowing the mice to tolerate the otherwise fatal administration of botulinum toxin.
Lead the toxin
Don and his colleagues needed to overcome two technical barriers that have prevented botulism from being effectively treated in the past. Interestingly, their solution was in the botulinum toxin itself.
“One of the barriers to treatment was crossing cell membranes, which is difficult with protein drugs,” explains Dr. Shinichiro Miyashita, a postdoctoral fellow in Don’s lab. “The other is targeting specific cell types, in this case specificity for motor neurons and nerve endings. Botulinum neurotoxins can naturally and efficiently target motor neurons and deliver protein cargo across cell membranes. I took advantage of the fact. “
Therefore, the treatment is two-sided. Botulinum toxin, which is detoxified by the introduced mutation, is the vehicle of delivery. The cargo, or active ingredient, is a mini-antibody derived from a camel antibody developed by Dr. Charles Shoemaker, a collaborator at Tufts University. The team has shown that two of these so-called Nanobodies can be delivered to neurons in tandem to neutralize botulinum toxin types A and B at once.
However, there was another problem to be solved.
“This idea and approach was tried, but it was difficult to completely eliminate the toxicity,” says Don. “Until we identify a new toxin, botulinum toxin X, in 2017. Unlike other botulinum toxins, this new toxin is not toxic. It acts as a safe delivery tool after introducing mutations. . “
Botox reversal
In addition to botulism, Don believes that new treatments may be useful as “botox reversal” agents. Botox injections with small doses of botulinum toxin can safely treat many other medical conditions such as wrinkles, neck cramps, excessive sweating, and overactive bladder. However, if the injection is unsuccessful, Botox can cause unwanted muscle paralysis as a side effect, and the patient must live with the paralysis for months.
“It may be possible to inject therapeutic proteins to get rid of neuronal botox and paralysis within hours,” says Don.
General delivery platform for neuroactive drugs?
Don believes that a toxin-inducing approach may provide a platform for incorporating biological agents into neurons to treat other disorders. Currently, most biological agents act only on cell surface targets and cannot enter the interior of the cell.
“We provide a protein-based drug delivery platform that enables highly specific targeting of neurons and efficient penetration of cell membranes,” says Dong. “In combination with Nanobodies, which are fairly easy to develop for proteins of interest, this platform can be used to develop therapies that regulate proteins and biological processes within neurons. Due to their modularity, non-neurons You can also target cell types other than neurons by switching between cell types. Cell targeting domains. This may present a general approach for precise drug delivery to cells. . “
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