THERAmolecular

THERAmolecular's
Research Agenda for 2024...

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Background: The prefix “THERA” implies wellness and specifically refers to healing “therapeutic” interventions or treatments, while the suffix “molecular” suggests such treatments result from fundamental research into the biomolecular mechanisms and processes supporting life. A major focus of THERAmolecular is our use of state-of-the-art “computer-aided drug design” (CADD) methods and software for streamlining and accelerating the drug discovery process.

Technology: During the past decade, major advances have occurred in computational modeling and simulation of drug properties and behaviors, especially with respect to how drugs interact (“dock”) with and inactivate (antagonist) or promote (agonist) specific “target” proteins (often called “receptors”) in the body that regulate a host of disease conditions. A good example of such protein targets are biotoxins (e.g., neurotoxins and proteolytic enzymes) produced by the “pit viper” family of snakes (e.g., rattlesnakes, cobras, copperheads, etc.). While the basic concepts behind CADD are easy to understand, the technology to implement those concepts are complex; and it requires cutting-edge software, as well as specialized computer hardware and algorithms to achieve success.

Hypertension: Over the past two years, our research has been primarily directed toward the discovery and optimization of new anti-hypertension drugs to help individuals suffering from high blood pressure and heart disease. We have recently demonstrated that some members of this important category of drugs also inhibit the replication of the SARs-CoV-2 virus in laboratory (tissue culture) tests. This work is ongoing and we expect to have to have exciting new results published in the next few months.

Inhibiting Pathogenic Biofilms with New Antibioics: Such biofilms are particularly important in the food preparation and packaging industry, invasive dental procedures (e.g., root canals and implants), as well as surgical implant devices, including joint replacements.

Inactivating Biotoxins: While the number of people who die each year in the US is limited due to the wide availability of snake venom antisera, globally (primarily in the tropics) there are more than 138,000 deaths annually from snake bites. THERAmolecular is actively seeking novel and inexpensive drugs that can be taken orally immediately following envenomation. View our Conference Presentation HERE.

Anti-Viral Drugs: The current pandemic has taught us that we need to remain vigilant and prepared to protect humanity from future and possibly more serious global viral outbreaks. Since the Spring of 2020, our research team has been deeply engaged in the search for new anti-viral drugs to combat the SARs-CoV-2 virus; and this work is continuing to this day. With this in mind THERAmolecular is expanding our search for more universal anti-viral drug therapies that will be safe, affordable and effective.

Parkinson's Disease and Related Nuerologic Disorders: Parkinson’s disease (PD) is a chronic neurodegenerative disorder of the central nervous system that degrades the function of both the motor and non-motor systems. Disease progression is generally (but not always) slow with cognitive and motor symptoms deteriorating with age. Early symptoms include tremors of the extremities (e.g., hands, feet, legs), rigidity affecting posture and balance, sluggish movement and difficulty with walking or running. However, over time, PD is associated with cognitive decline (including onset of depression and/or dementia), behavioral changes, sleep deprivation and changes in sensory systems (especially smell, hearing). In more severe or advanced stages, involuntary motor functions, such as breathing and gastrointestinal functions can be affected.

Parkinson’s is a member of the so-called “Lewy Body diseases”, also referred to as a “synucleinopathy” because it is characterized by deposits of α-synuclein protein in the brain. The synucleinopathies comprise dementia with Lewy bodies and progressive multiple system atrophy, however, rare genetic forms of Parkinson's do not exhibit alpha-synuclein aggregation.

PD is the second most common neurodegenerative disorder affecting seven million people globally. It is currently the fastest growing neurodegenerative disease in both prevalence and death. PD is more common in the elderly with rates rising from ~1% in those over 60 to 4% over 80. The number of new diagnoses per year of PD is between 8–18 per 100,000.

PD is associated with cell death in the basal ganglia, with up to 70% of the dopaminergic (dopamine-secreting) neurons in the substantia nigra pars compacta (SNPC) being destroyed by the end of life. At a cellular and molecular levels, PD is characterized by Lewy-Body (LB) accumulation resulting from mis-folding and aggregation of α-synuclein. LB is cytotoxic and results in neuronal damage and eventually cell death. PD originates in the medulla and the olfactory bulb, subsequently migrating to the SNPC and the rest of the midbrain/basal forebrain. Motor symptoms are triggered when the disease begins to affect the SNPC.

While there are several drugs to slow the progression of PD, there remains no cure. Our research is currently focused on the design and optimization of small-molecule drugs that can cross the blood-brain barrier (BBB) and inhibit the enzyme monoamine oxidase-b (MAOB), which degrades the neurotransmitter L-dopamine. Inhibition of this enzyme increases brain and peripheral system dopamine levels, thereby stimulating and maintaining neurologic function and suppressing cognitive and physical decline. As of this writing, THERAmolecular has identified a novel class of MAOB inhibitors that exhibit superior binding to the catalytic domain of MAOB, suggesting they may perform better than MAOB drugs currently marketed, including safinamide, selegiline and rasagiline, which have significant side effects. As we pursue this line of research we will seek to re-design and optimize drug specificity and effectiveness while minimizing side effects.