To treat some of the psychosis problems associated with Parkinson’s disease, doctors often prescribe pimavanserin, an antipsychotic drug that works in the brain to prevent hallucinations and delusions. Due to its ability to prevent or reduce these symptoms, pimavanserin has also been studied as an antipsychotic treatment for other neurological conditions such as Alzheimer’s disease, schizophrenia, and depression.
For 20 years, Sanjay Srivastava, Ph.D., has researched existing drugs to determine if they can be reused to treat conditions other than those for which they were developed and approved. For most of the past decade, his research has focused on investigating non-cancer drugs that can be reused to treat various cancers.
Those efforts recently earned Srivastava a US patent for reusing pimavanserin to treat various cancers. Srivastava, chair of the Division of Immunotherapeutics and Biotechnology at the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, said the patent, titled “Compositions and Methods for Treating Cancer,” extends all of the drug’s uses to the drug. area of cancer.
“With this patent, we can cover all variants,” he said. “If we change the structure of this compound, that’s covered (by the patent), and if we make a formulation, that’s covered too. If someone wants to use pimavanserin as a cancer therapy, our patent should be considered part of that process.” for drug development, because in fact all the different aspects associated with this drug are covered by this patent.”
Srivastava began the research that led to the patent by examining non-cancer drugs that he believed had the potential for treating brain cancer. He said the rationale behind drug reuse is that these drugs are already approved and used by patients in the clinic.
“If we find a new target for these drugs in different disease models, we can speed up the process and get the drugs to the patients much faster,” Srivastava said. “During our preclinical evaluation, we have gained a comprehensive understanding of the clinical perspective of these recycled drugs, which could save us a tremendous amount of time and money.”
Srivastava said the main hurdle to treating brain tumors is finding an effective drug that can cross the blood-brain barrier. Formed by cells that line the blood capillaries that supply parts of the central nervous system, including the brain, the blood-brain barrier is a semipermeable barrier responsible for protecting the brain from substances that can be harmful. This includes regulating or preventing the transfer of some drugs and chemicals from the blood to the brain.
“The blood-brain barrier is a good thing, but the downside is that some drugs can’t cross the barrier and are then ineffective,” he said.
Because antidepressants and antipsychotics can cross the blood-brain barrier and reach the brain, Srivastava and his team initially studied penfluridol as a potential treatment for brain cancer. Penfluridol is a first-generation antipsychotic drug that became available in the late 1960s for the treatment of chronic schizophrenia, acute psychosis, and Tourette’s syndrome.
Several years after their studies, Sharavan Ramachandran, Ph.D., one of Srivastava’s former graduate students, found that pimavanserin, a new drug at the time, suppressed the growth of some cancer cells, including pancreatic cancer cells. His research eventually found that pimavanserin has the ability to suppress the growth of several other cancer cells, including those associated with pancreatic and brain tumors.
To take their research to the next level, Ramachandran, who is credited as co-inventing the patent, planted tumors in the brains of mice and then treated the mice with pimavanserine. The findings showed that pimavanserin significantly suppressed brain tumor growth in animal models.
“That was very exciting for us,” said Srivastava. “We immediately applied for a patent for its application in cancer, because no one had ever demonstrated the cancer-fighting effect of pimavanserin; it was only used for the psychosis of Parkinson’s disease. What sets pimavanserin apart from other cancer antipsychotic drug candidates is its high selectivity for the 5-HT2A receptor (serotonin). This property makes pimavanserin one of the few second-generation antipsychotics with potentially low toxicity.”
When Srivastava presented his team’s findings at a cancer research conference in Chicago, he was immediately contacted by major pharmaceutical companies involved in pimavanserin. Discussions are underway on partnership and development efforts with industry, both nationally and internationally. The Office of Research Commercialization continues commercialization strategies and partnership discussions as it continues to build a strong patent portfolio around the technology, a necessity for any drug to reach the market.
Srivastava and his team are also seeking clinical partners to conduct a short-term window-of-opportunity trial with pimavanserin in patients awaiting surgery or other therapies. He is particularly interested in seeing how the drug works in patients with glioblastoma, a type of brain tumor that he described as almost a death sentence for patients. Those patients are currently being treated with temozolomide, a chemotherapy drug that can extend a patient’s life, but does not cure the cancer.
“We have shown in our study that pimavanserine can enhance or enhance the effect of temozolomide by inhibiting certain proteins responsible for causing resistance to temozolomide in cases of glioblastoma,” he said.
In addition to raising funds for the studies, Srivastava said his team needs to identify clinicians willing to participate in the studies so they can determine whether or not pimavanserin has an active effect against cancer in humans. Once the trials are scheduled, Srivastava said it generally takes at least five years for researchers to be sure the drug isn’t causing significant side effects for patients and is effective.
Since pimavanserin is already approved for use in humans, that timeframe could speed up, but Srivastava said there’s no way to predict when the drug may be available to cancer patients until the clinical trial process is complete.
“This is why I hope we can get the support of some clinicians to conduct clinical trial trials in some patients,” Srivastava said.