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Cardiology

Innovative Stroke Treatment Leads

to Novel Patent Applications for FAU Neuroscientist

Jang-Yen (John) Wu, Ph.D., distin- “The most central mechanisms of tis- Many neurological disorders such as researchers studied Carbamathione to
guished professor of biomedical science sue damage in stroke are scarcity of oxy- Alzheimer’s disease, Parkinson’s disease test their hypothesis that it provides neu-
and neuroscientist in the Schmidt gen or hypoxia, glucose, excitotoxicity, as well as stroke have been related to the roprotection like DETC-MeSO by
College of Medicine at Florida Atlantic the excess release of glutamate from over-activation of glutamatergic trans- inhibiting apoptosis and endoplasmic
University, has filed a patent application affected cells, and production of injuri- mission and excitotoxicty as a known reticulum stress in the brain in a rodent
with the U.S. Patent and Trademark ous free radicals. Stroke causes a flow of pathway of neuronal injury. model of stroke.
Office (USPTO) for a novel agent that is events that can provoke the glutamate Carbamathione has an antagonistic “Results from our study show that
showing real promise for the treatment release and increase free radical produc- effect on brain glutamate receptors and Carbamathione is a very effective agent
of stroke. Researchers at FAU conducted tion via numerous different pathways,” Disulfiram has been demonstrated that it for protecting cells from hypoxia/re-oxy-
in vitro and in vivo studies to test the said Wu. “Our research provides neuro- exerts its anti-alcohol effect only after genation induced cell damage, which we
agent, Carbamathione, S-(N, N-diethyl- protective evidence that Carbamathione bio-activation to the active metabolite think may be due to the inhibition of
carbamoyl) glutathiones, an active could protect against excitotoxicity dam- DETC-MeSO. Carbamathione on glutamate receptors,”
metabolite of Disulfiram, which has been age by preserving mitochondrial and In prior studies, Wu and collaborator said Wu.
used for decades to treat alcohol-use dis- endoplasmic reticulum function in the Howard Prentice, Ph.D., a professor of “Carbamathione may play a dual role
order. They discovered that brain of ischemia.” biological sciences in FAU’s College of in preventing hypoxia-induced cell
Carbamathione could be used to treat Stroke or ischemia leads to a rise in the Medicine, identified an important neuro- death, in which it could suppress the
conditions associated with hypoxia – a extracellular concentrations of excitatory protective role for DETC-MeSO and two glutamate release from the presynaptic
lack of oxygen to tissues – such as stroke. amino acids, largely in glutamate. other FDA-approved drugs, Sulindac and sites of neurons and the activation of glu-
It has been demonstrated that more than Glutamate is the key excitatory neuro- G-CSF, used to enhance blood cellular tamate receptors post-synaptically on
60 percent of patients acquire hypoxia transmitter. In small amounts it is crucial development and neuronal regeneration. neurons.”
within the first 60 hours after a stroke. for normal function, however, in extreme Wu and Prentice discovered that each The stroke discoveries by Wu and
In addition, Wu has filed a patent amounts it is a neuronal poison or toxin agent individually produced potent pro- Prentice are being developed by CHS
application with the USPTO for called excitotoxin. It is thought that survival responses. Furthermore, the Pharma, Inc., a South Florida-based
Granulocyte colony-stimulating factor brain ischemia followed by glutamate combination of these three drugs also biotechnology development company
(GCSF), a novel gene therapy for stroke excitotoxicty leads to intracellular calci- resulted in strong neuroprotection even that has an intellectual property portfolio
and Alzheimer’s disease. This unique um overload and initiates a series of when the agents were employed at low for potential treatments related to
therapy could provide a long-term and intracellular events, such as the release doses compared to the respective stan- ischemic stroke, dry macular degenera-
sustainable supply of GCSF for the treat- of apoptotic proteins leading to apoptot- dard drug doses. They patented this tion and other age-related disorders such
ment of these diseases. ic cell death. novel approach earlier this year. The as Alzheimer’s disease.

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22 February 2019 southfloridahospitalnews.com South Florida Hospital News