Many essential technologies utilize radioactive material, including food and medical sterilizers, X-ray and radiotherapy sources, and even household smoke detectors. In addition, radioactive material drives nuclear power plants, space vehicles, and nuclear weapons. Exposure to radioactive material of almost any kind, particularly when it is internalized within the body, presents a serious health risk.
The global threat level for a nuclear reactor catastrophe is arguably as high as it has ever been. Additionally, once-dwindling support for nuclear power has reversed in the face of a pressing need for clean energy, with Germany, California, and Japan announcing plans to extend or restart operation of their nuclear energy infrastructure (read). Finally, adversarial nations continue to develop their weapons capabilities, and with them the ever-present specter of a nuclear detonation somewhere around the world.
There is currently no useful treatment for people exposed to radioactive actinide elements like plutonium, uranium, or americium - the actinides of highest concern following a nuclear reactor accident, detonation, or intentional dispersal device (“dirty bomb”). The only FDA-approved countermeasure for such contamination - DTPA - must be administered by IV injection, and is no longer manufactured.
As an orally-available therapeutic, HOPO-101 has been designed to be self-administered. It has been developed for inclusion in disaster preparedness programs such as the US Strategic National Stockpile, and for rapid introduction to a contamination zone. It has shown best-in-class preclinical efficacy for both the prevention and treatment of plutonium and americium contamination.
In addition to government stockpile programs aimed at protecting civilian populations, potential military uses include readiness for deployment of tactical nuclear weapons, battlefield exposure to depleted uranium munitions and other heavy metals, and personnel health security aboard nuclear-powered warships and submarines. Prospective non-government partners include utility companies; manufacturers, distributers, and hospital pharmacies in the nuclear medicine ecosystem; and other organizations whose workforces face potential exposure to radioactive materials.
Over 800 million children worldwide are currently living with lead poisoning. A toxic heavy metal, lead causes 30% of worldwide cases of idiopathic developmental disabilities, 5% of cardiovascular disease, and 3% of chronic kidney disease, according to the WHO. All together, lead is responsible for almost half of the 2 million annual deaths caused by known chemical exposure around the world.
Lead poisoning through 2015 has cost the current U.S. population nearly 825 million IQ points, or about 2.6 IQ points per adult. The economic impact of childhood lead poisoning on low- and middle-income countries is almost $1 trillion, and in Africa is nearly 4% of continental GDP.
The global health impact of lead poisoning - over 1 billion people - is comparable to malaria or HIV, however there has been no innovation in treatment for decades. While chelation therapies do currently exist, limitations in efficacy and safety restrict their use to only the most severely poisoned, leaving over 99% of all patients without any available treatment. While much of the world’s lead poisoning occurs in low- and middle-income countries, the CDC estimates that there are about 500,000 children in the U.S. living with lead poisoning, and that minority populations are disproportionately impacted. A manifestation of environmental racism, a 2020 study concluded that “being Black is a bigger risk factor for lead poisoning [in the U.S.] than poverty or poor housing”. Left untreated, the negative heath, social, and economic consequences associated with lead poisoning will continue to drive the existing disparities in overall outcomes that affect minority communities throughout the U.S.
There is no level of lead that is safe in the body. Levels as low as 1 µg/dL are associated with cognitive impairment, and the severity increases with exposure.
Children are particularly vulnerable to the dangerous effects of lead poisoning. When young children are exposed, they absorb 4-5 times more lead than adults, and can suffer profound and lifelong health impacts. Normal hand-to-mouth behavior results in children ingesting lead-containing dust or lead-coated objects, amplifying the impact of lead in the body. At low levels of exposure, lead can cause a spectrum of damage, including slowed brain development, reduced IQ, behavioral changes, reduced attention span, violent behavior. Lead can also cause anemia, hypertension, and damage to reproductive organs later in life.
Lead mimics the behavior of calcium in the body, and during pregnancy and menopause the normal mobilization of calcium can reintroduce lead into a woman’s bloodstream. This is particularly concerning during pregnancy, as lead is known to cross the placental barrier, exposing the developing child in utero. While the long-term health effects of lead recirculation are still not fully understood, lead is a known neurotoxin and also increases the risk of cardiovascular disease. Approximately 99% of people born in the U.S. between 1956-1980 had lead poisoning as children, placing the women of these birth cohorts at risk for increasing blood lead levels during and after menopause.
Based on available data, our investigational therapeutics are likely capable of achieving a meaningful reduction of lead levels in children, both as a preventative prophylactic, or for post-exposure therapy. Any circulating lead is also likely a viable target.
Heavy metals are utilized in a number of medical technologies, including chemotherapies like cisplatin and gadolinium-based MRI contrast agents. In nuclear medicine, certain radioactive metal isotopes are used to enable quantitative PET imaging, while the cell-killing power of other isotopes can be used to destroy cancer cells with radioligand therapy.
The clinical successes of radioligand therapies has prompted a boom in both R&D and M&A activity to rush new treatments to market. Particularly in the case of drug candidates using the isotope actinium-225 (Ac-225), the chelating agents that are currently used to bind these heavy metals to their targeting vector require lengthy heating and purification steps, adding significant time and expense to manufacturing and distribution. These inefficiencies, brought on by suboptimal metal binding chemistry, pose large obstacles to the successful scaling of these life-saving treatments
With a highly optimized binding capability for a range of radioactive heavy metals, HOPO-101 and its related chelating agents can be used to dramatically streamline the manufacturing of radioligand therapies, reducing both cost of treatment and the time required to manufacture. Incorporating our chelating agents into a
protein-based delivery platform for therapeutic and diagnostic isotopes
may enable a transformative, “cold kit” synthetic approach to the next generation of radioligand therapies and PET diagnostic agents.
For people with elevated risk who require a contrast MRI, every effort should be made to prevent or mitigate gadolinium deposition after the MRI is completed. Removal of residual gadolinium via a targeted chelating agent is the only practical treatment, although alternatives such as hemodialysis have been considered. In preclinical studies, HOPO-101 enabled the effective prevention of gadolinium deposition when administered up to 48 hours following gadolinium exposure. Patients with kidney disease, as well as children, pregnant women, and those needing multiple contrast MRIs may consider a prophylactic or preventative treatment to minimize the amount of gadolinium retained in their body.
The effects of gadolinium deposition in the body are also cumulative, so patients that require repeated contrast MRIs to monitor diseases such as brain cancer or multiple sclerosis may have progressively increasing levels of retained gadolinium. Finally, some patients develop debilitating symptoms after sometimes just a single GBCA adminsitration, and have detectable gadolinium in their urine for months to years following the MRI.
There is currently no way to prevent or treat gadolinium deposition from GBCAs. The diagnostic benefits of the contrast MRI are generally accepted to outweigh the risks associated with deposition, as the toxicity profile of gadolinium is not well-understood. The risks for exposure to gadolinium are higher in certain populations, including those with impaired kidney function, children, and pregnant women.
Treatment may also be possible for people who have already developed symptoms from GBCA exposure. The specific causes of symptoms - often thought to be fibrotic and/or neurological - are currently not well-understood, however gadolinium is a known toxin. Therefore it is logical to remove as much gadolinium as possible from the body via chelation, provided it can be done safely.
HOPO-101 and all related products described on this site are STRICTLY INVESTIGATIONAL and have not been shown to be safe OR effective in any clinical trials. The statements made herein are based solely on studies carried out in animals and reflect the best good faith scientific assessment of the company and its management and scientific personnel. None of these statements have been evaluated by the FDA, and HOPO-101 is not FDA-approved for any use or indication. Additional studies are necessary before any definitive conclusions can be made.