RespireRx Pharmaceuticals Inc. Announces the Publication of a Case Report in which KRM-II-81 Totally Suppressed Epileptiform Activity in Brain Tissue Surgically Removed from Epileptic Patient
Glen Rock, N.J., Jan. 04, 2024 (GLOBE NEWSWIRE) — RespireRx Pharmaceuticals Inc. (OTC Pink Market: RSPI) (“RespireRx” or the “Company”), a leader in the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is pleased to announce the publication of a case report in Heliyon, Cell Press’s peer-reviewed journal (available at https://www.cell.com/heliyon/pdf/S2405-8440(23)10960-1.pdf) involving a 19-year old patient with pharmaco-resistant epilepsy. As is often the case with such patients, tolerance developed to the standard anti-epileptic treatments, rendering them ineffective, and the patient required a craniotomy in order to remove the brain tissue responsible for the seizure generation. One year after surgery, the patient remains seizure free, but remains on medication.
Cortical brain tissue surgically resected from the patient exhibited epileptiform bursting with microelectrode recordings. When KRM–II–81, one of our lead GABAkines, was added the incubation fluid, the epileptiform activity in the excised brain tissue was fully suppressed. KRM–II–81 is a novel α2/3 subtype preferring GABAA receptor potentiator that previously demonstrated anti-epileptic efficacy in multiple animal models of epilepsy as well as a lack of drug tolerance and reduced undesirable side-effects. These findings add translational support to the proposition that KRM–II–81 might reduce seizure burden in pharmaco-resistant patients.
Jodi L. Smith, PhD, MD, FAANS, Director, Pediatric Neurosurgery at Peyton Manning Children’s Hospital at Ascension St. Vincent Medical in Indianapolis, IN led this research effort and is quoted as saying, “I am happy to report that a year after the surgery the patient is seizure-free but remains on seizure medication. Although our research team has observed suppression of activity previously in cortical tissue from epileptic patients, we have now observed recurrent epileptiform bursting in this patient’s tissue. KRM-II-81 fully suppressed the epileptiform bursting, which returned when KRM-II-81 was removed from the incubation medium. We feel that this observation is an impressive indicator for success in translation to patient treatment for this compound.”
The manuscript’s corresponding author Rok Cerne, MD, PhD, Senior Research Fellow with RepireRx, said that “the bursting activity across a neural network is a unique signature of epilepsy that we were able to observe in the cortical tissue from this patient. Prior to surgery, this 19-year-old patient suffered from seizures in the presence of multiple standard anti-seizure medications. The complete abolishment of these epileptic bursts by our GABAkine is one of most impressive demonstrations we have made to date with KRM-II-81. The data are highly encouraging for us to continue with IND enabling animal studies conducted in collaboration with the National Institutes of Health and to move into the clinic with KRM-II-81.”
Epilepsy is a highly prevalent, life-disrupting and life-threatening neurological disorder for which about 30% of the millions of patients worldwide do not respond to treatment. It is for this reason that research efforts such as ours continue with the search for safe and more effective antiseizure medications. The present research finding, along with a large data base of preclinical studies, predicts that KRM-II-81 will be effective in those patients not treated successfully with standard of care medicines. The additional possibility of a non-sedating and non-addicting profile along with the lack of tolerance development adds to our confidence in moving KRM-II-81 forward into patient clinical trials.
About RespireRx Group
RespireRx Pharmaceuticals Inc. and its subsidiaries and business units (“RespireRx Group”) are discovering and developing medicines for the treatment of psychiatric and neurological disorders, with a focus on treatments that address conditions affecting millions of people, but for which there are few or poor treatment options, including epilepsy, pain, attention deficit hyperactivity disorder (“ADHD”), recovery from spinal cord injury (“SCI”), certain neurological orphan diseases and obstructive sleep apnea (“OSA”). The RespireRx Group is developing a pipeline of new and repurposed drug products based on our broad patent portfolios for two drug platforms: (i) neuromodulators, which include GABAkines and AMPAkines, proprietary chemical entities that positively modulate (positive allosteric modulators or “PAMs”) GABAA receptors and AMPA-type glutamate receptors, respectively, and (ii) pharmaceutical cannabinoids, which include dronabinol, a synthetic compound that acts upon the nervous system’s endogenous cannabinoid receptors.
The RespireRx Group holds exclusive licenses and owns patents and patent applications or rights thereto for certain families of chemical compounds that claim the chemical structures and their uses in the treatment of a variety of disorders, as well as claims for novel uses of known drugs.
EndeavourRx: Neuromodulators
GABAkines. Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. (“UWMRF”) and on behalf of its EndeavourRx business unit, RespireRx has licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific, subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. EndeavourRx currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.
KRM-II-81 has displayed a high degree of anti-convulsant activity in a broad range of preclinical studies, including in treatment resistant and pharmaco-resistant models. Not only was KRM-II-81 highly effective in these models, but pharmaco-resistance or tolerance did not develop to its anti-convulsant properties. These latter results are particularly important because pharmaco-resistance occurs when medications that once controlled seizures lose efficacy as a result of chronic use and it is a principal reason some epileptic patients require brain surgery to control their seizures. In support of its potential clinical efficacy, translational studies have demonstrated the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ to brain slices excised from treatment resistant epileptic patients undergoing surgery.
In addition, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In intact animal models of pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.
AMPAkines. Through an extensive translational research effort from the cellular level through Phase 2 clinical trials, RespireRx has developed a family of novel, low impact AMPAkines, including CX717, CX1739 and CX1942 that may have clinical application in the treatment of CNS-driven neurobehavioral and cognitive disorders, spinal cord injury, neurological diseases, and certain orphan indications. Our lead clinical compounds, CX717 and CX1739, have successfully completed multiple Phase 1 safety trials. Both compounds have also completed Phase 2 proof of concept trials demonstrating target engagement, by antagonizing the ability of opioids to induce respiratory depression.
AMPAkines have demonstrated positive activity in animal models of ADHD, results that have been extended translationally into statistically significant improvement of symptoms observed in a Phase 2 human clinical trial of CX717 in adult patients with ADHD. Statistically significant therapeutic effects were observed within one week. We believe AMPAkines may represent a novel, non-stimulant treatment for ADHD with a more rapid onset of action than alternative non- stimulants, such as Straterra® (atomoxetine), and without the drawbacks of amphetamine-type stimulants.
In a series of important studies funded by grants from the National Institutes of Health and published in a number of peer reviewed articles, Dr. David Fuller (University of Florida), a long-time RespireRx collaborator, has demonstrated the ability of CX1739 and CX717, RespireRx’s lead AMPAkines, to improve motor nerve activity and muscle function in a number of animal models of spinal cord injury (SCI).
ResolutionRx: Pharmaceutical Cannabinoids.
ResolutionRx Ltd (Australian Company Number a/k/a ACN 664 925 651) was formed in Australia on January 11, 2023 by RespireRx as an unlisted public company. RespireRx has contributed by sublicense and license with ResolutionRx, its sleep apnea drug development program subject to certain liabilities. ResolutionRx now engages in the research and development (“R&D”) associated with that program, initially for the development of a new formulation of dronabinol for use in a Phase 3 clinical trial and the filing of regulatory approval for the treatment of obstructive sleep apnea (“OSA”). The current total budget for that program over the next several years is approximately US$16.5 million, most, but not all of which is expected to be eligible for the Australian R&D Tax Incentive (“RDTI”). Dronabinol, an endocannabinoid receptor agonist, has already demonstrated significant improvement in the symptoms of OSA in two Phase 2 clinical trials. OSA is a serious respiratory disorder that impacts an estimated 90 million people in the United States, the United Kingdom, Germany and Australia and has been linked to increased risk for hypertension, heart failure, depression, and diabetes. There are no approved drug treatments for OSA.
Because dronabinol is already FDA approved for the treatment of AIDS related anorexia and chemotherapy induced nausea and vomiting, RespireRx and ResolutionRx further believe that its repurposing strategy would only require, in the United States, approval by the FDA of a 505(b)(2) new drug application (“NDA”), an efficient regulatory pathway that allows the use of publicly available data.
Additional information about RespireRx and the matters discussed herein can be obtained on the RespireRx website at www.RespireRx.com or RespireRx’s filings with the U.S. Securities and Exchange Commission (the “SEC”) at www.sec.gov. Additional information about ResolutionRx and the matters discussed herein can be obtained on the ResolutionRx website at https://www.resolutionrx.com.au.
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Company Contact:
Jeff Margolis
Senior Vice President, Chief Financial Officer, Treasurer and Secretary
RespireRx Pharmaceuticals Inc.
126 Valley Road, Suite C
Glen Rock, NJ 07452
Telephone: 917-834-7206
Email: jmargolis@respirerx.com
www.respirerx.com
