Research Roundup: Brain Inflammation in Monkeypox, Repurposing Drugs for Autism & More
16 Sep 2022
AntibodyImmunotherapy
Neuronal Inflammation was found in two U.S. monkeypox patients, researchers short-list four drugs for potential study in autism, a new test can predict immunotherapy outcomes and a new radiopharmaceutical venture is born.
Two Cases of Monkeypox-related Neuronal Inflammation Reported
Two monkeypox patients in the U.S., one in Colorado and one in Washington, DC, have developed encephalomyelitis, or inflammation of the brain and spinal cord.
The neurological complications developed one week after the onset of their symptoms for both individuals, suggesting the inflammation may be the outcome of their monkeypox infections.
The cases were reported Tuesday in Morbidity and Mortality Weekly Report.
The Colorado-based patient is an immunocompetent, gay man in his 30s with no known monkeypox exposure or international travel.
Nine days after symptom onset he developed progressive left arm and leg weakness and numbness followed by urinary retention issues and intermittent priapism. He was hospitalized shortly after these symptoms began and treated with Tpoxx. Weakness in his left leg lasted over one month during which he required walking assistance.
The DC case belonged to an otherwise healthy gay man in his 30s who similarly had no known exposure to monkeypox or recent travel. His abnormal symptoms began five days after the original monkeypox symptom onset.
He experienced similar symptoms to the first patient, with bowel and bladder incontinence and progressive weakness in both legs. He was hospitalized and eventually intubated and admitted to the ICU. He was treated with Tpoxx and later rituximab, a monoclonal antibody medication.
“The underlying pathology behind this is unclear but might represent either MPXV invasion of the [central nervous system] or a parainfectious autoimmune process triggered by systemic MPXV infection,” the study authors stated.
While rare, outcomes similar to these were seen during smallpox outbreaks centuries ago, the Center for Infectious Disease Research and Policy noted.
Researchers Shortlist Four Drugs for Study in Autism
Researchers have found four drugs that, while currently used to treat other disorders, may be useful in treating the core symptoms of autism spectrum disorder (ASD).
ASD is characterized by social and communication deficits. It is known to be highly hereditary and clinically heterogeneous. As of now, there are no medications approved for the treatment of these primary symptoms.
The researchers, from the University of Oslo and Aarhus University in Denmark, studied ASD risk genes within networks of protein-protein interactions of gene products.
The aim was to evaluate if various drugs, typically used to treat other disorders and symptoms, may change the ASD-associated gene expression in this network. The logic behind this process was that if a drug did change the expression, it could be used to treat core ASD symptoms, and should be further investigated.
The researchers narrowed their list of potential drugs down to four: Loperamide, bromocriptine, drospirenone and progesterone. These drugs act on ASD-related biological systems, indicating they could be useful in treating the core symptoms of ASD.
In conclusion, the researchers shortlisted these four drugs for potential clinical translation in ASD.
Single Test can Predict Immunotherapy Outcomes
Researchers at NYU Grossman School of Medicine’s Perlmutter Cancer Center have identified a single test with the potential to predict severe side effects and recurrence in patients treated with immunotherapy.
The test centers around autoantibodies found in a patient’s blood prior to immunotherapy. The human body recognizes tumors as abnormal. But, the cancerous cell hijacks the body’s defense checkpoints and turns off the immune attack at the PD-1 receptor (programmed death receptor 1).
PD-1 inhibitorsPD-1 inhibitors have been effective against many cancers but many patients still experience disease recurrence and severe treatment-related side effects, the researchers noted.
Studying two checkpoint inhibitors, Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab), the team identified a panel of distinct autoantibody signatures with the ability to predict immune-related adverse effects.
While the data support the predictive nature of these autoantibody scores, more research is needed before the test can be used in clinical settings, the researchers said.
Radiopharm Ventures Launches
The University of Texas MD Anderson Cancer Center and Radiopharm Theranostics have launched Radiopharm Ventures to develop radiopharmaceutical therapeutics for the treatment of cancer.
"Radiopharmaceuticals continue to be rapidly developed as a highly promising therapeutic frontier in oncology," said Riccardo Canevari, chief executive officer of the new venture in a statement.
Radiopharmaceuticals work by delivering small doses of radiation to specific cell targets for therapeutic or diagnostic purposes. The process requires tumor-specific targets. MD Anderson brings novel platforms to discover and validate tumor-specific antigens, the companies stated.
A humanized immunoglobulin G (IgG) antibody targeting the tumor-specific antigen B7-H3 (CD276) was presented as the potential first candidate. The radiotherapeutic antibody has shown evidence of efficacy in eliminating resistant colorectal cancers in laboratory models.
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