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Engineered Parasites as Potential Treatments for Neurological Disorders
This post is written by guest author Apurva Singh
Due to the severity and lack of effective treatments for many neurological disorders, scientists are exploring alternative therapies—Rett syndrome being one such rare, complex, and deeply challenging condition. Combined with its progressive symptoms, makes it a key focus for alternative therapeutic strategies. A rare genetic neurological condition that predominantly affects females,it is caused by alterations in the MECP2 gene, which is crucial for proper brain development. Typically, children with Rett syndrome grow and develop normally for the first 6 to 18 months of life. After which they start to lose skills they’ve recently acquired, such as speech, intentional hand movements, and motor coordination. Common symptoms include repetitive hand movements, irregular breathing patterns, difficulties with balance, and seizures. While the disorder is associated with a genetic mutation, the majority of cases occur spontaneously and are not passed down from parent to child.
Parasites as brain therapies
Traditionally seen as harmful, parasites are now being reimagined as therapeutic tools, thanks to advances in neuroimmunology and synthetic biology. Researchers are genetically modifying parasites especially Toxoplasma gondii—to regulate immune responses, deliver drugs, cross the blood-brain barrier (which normally restrict the passage of large molecules) and cerebrospinal fluid(whose circulation clears drugs before they reach the neurons) .These modified organisms are being explored as minimally invasive, targeted treatments for brain disorders where inflammation and immune dysfunction play key roles.
Why parasites?
Certain parasites have the extraordinary capacity to enter, persist, and interact with brain tissue—features that conventional medication delivery methods frequently struggle to duplicate. Scientists are looking for ways to turn these once-dreaded organisms into precise, living vehicles for delivering medication directly to the brain by utilizing these natural qualities.
(A) Key brain barriers including BBB (Blood brain barrier)and CSF(cerebrospinal fluid) interfaces.
(B) T. gondii crosses BBB via capillaries, interacting with endothelium, pericytes, and astrocytes.
Image from the original article
The study’s major achievement was the successful introduction of the MeCP2 protein, a key regulator of gene expression and a treatment target for Rett syndrome into the brains of affected mice. To achieve this, researchers modified Toxoplasma gondii by attaching proteins like toxofilin and GRA16 to other molecules (with fluorescent markers or epitope tags).Toxofilin and GRA16 were selected due to their natural export by Toxoplasma gondii into host cells, facilitating the successful fusion and delivery of MeCP2 into the host cell milieu for tracking and functional investigations.
These tags emit light (in the case of fluorescence) or can be recognized by specific antibodies, allowing researchers to visualize where the protein goes inside the cell under a microscope and track its interactions or effects in real time. They also changed the parasite’s natural secretion mechanisms, which include rhoptries – club-shaped structures used by parasites to secrete proteins. This alteration enabled the parasite to introduce several big proteins (>100 kDa) into neurons. The study demonstrated effective administration in brain organoids, cultured cells, and living mice, highlighting the parasite’s potential as a delivery system for neurological treatments. Rett syndrome and potentially other neurological conditions associated with protein deficiencies or malfunctions may be treated using this approach.
The drawbacks
However, using T. gondii as a delivery system has its own set of difficulties. Given the parasite’s capacity to cause illness, safety concerns are crucial. The study addressed this by using less dangerous, weakened strains of T. gondii and by genetically modifying the parasites to create medicinal proteins without causing disease. To verify this method’s long-term safety and efficacy in humans, more research is necessary.
Additionally, a comprehensive evaluation of the immunological response triggered by the parasite and its constituents is necessary. Even though T. gondii infections usually don’t cause any symptoms, the immune response that follows may affect how well the therapeutic proteins are delivered.Future research should concentrate on methods to reduce potential immune reactions, like using immunosuppressive medications or altering the parasite further to reduce its immunogenic qualities.
In conclusion, Toxoplasma gondii modification for the direct delivery of therapeutic proteins into neurons is a novel and perhaps successful strategy for treating neurological conditions. Researchers have created new avenues for the focused, effective, and long-term administration of treatments to the brain by utilizing the parasite’s inherent advantages and modifying its secretion mechanisms. Even if there are still challenges, especially with regard to safety and immunological reactions, the potential benefits of this approach make further study and development worthwhile. Engineered parasites like T. gondii may develop into vital tools in the fight against serious neurological conditions as research progresses
Featured image: Image from article
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