Unmet Need: Toxoplasmic Encephalitis (TE) is a life-threatening central nervous system (CNS) disorder that results from the reactivation of a chronic brain infection with Toxoplasma gondii. Chronic T. gondii infection poses a constant and severe danger in situations of immunodeficiency as can occur in HIV infection, organ transplantation, or cancer chemotherapy. Disease burden will likely increase as immunosuppression for solid-organ and stem-cell transplant patients becomes more frequent in the United States and other areas of the world. Because TE progresses rapidly, early diagnosis is crucial for optimal patient outcomes.
The primary diagnostic assay for TE is a quantitative polymerase chain reaction (qPCR) assay that targets the multicopy B1 gene and AF146527 elements. However, because T gondii infection is located in the brain, direct measurement of infection is difficult. Toxoplasma DNA can be detected in cerebral spinal fluid (CSF) and blood from symptomatic patients with TE. However, the use of these assays is generally limited to the time of diagnosis. They offer little predictive value in determining risk of infection. Due to the rapid onset and often fatal nature of TE, there exists an unmet need to design a robust diagnostic tool to determine risk of TE in immunocompromised populations.
Technology Overview: Inventors at Johns Hopkins developed a non-invasive method for predicting the risk of TE via a serological assay for antibodies to a chimeric MAG1 antigen specific for the chronic phase of the Toxoplasma parasite. Preliminary data support the predictive value for TE of a positive test up to 2 years prior to the clinical diagnosis of TE in patients with HIV.
The invention could support closer clinical monitoring for determining when aggressive prophylactic or therapeutic therapy is appropriate.
Stage of Development
1. The serological assay employs synthetic peptides which can be produced economically with ultra-high purity and in large quantities.
2. The synthetic peptides are chimeric antigens with linkers between different regions of the MAG1 protein. The antigens were identified through a combination of bioinformatics analysis of protein antigenicity and empirical studies.
3. The inventors demonstrate the predictive value of the MAG1 assay for TE in HIV infected patients several years prior to clinical diagnosis.
4. Commercialization of the technology will require development of an optimized ultrasensitive immunoassay and determination of predictive value for TE in defined clinical populations
Publication
1. Jianchun Xiao, et al., Serological Responses to Toxoplasma Gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Enchephalitis in People Living with Human Immunodeficiency Virus (HIV). Clinical Infectious Diseases
