By Daniel Dunaief
It worked for mice and now, several years later, has shown promise for cats.
Researchers from Maurizio Del Poeta’s lab, working closely with those from Iwao Ojima’s team at Stony Brook University, have demonstrated that an experimental treatment against a fungus resistant to the current standard of care can work with cats battling a ferocious infection, albeit on a small sample size.
The Stony Brook team, along with scientists and veterinarians in Brazil, used a drug they created in 2018 called D13 to treat 10 cats with severe forms of a fungus that affects cats and humans called sporotrichosis.
With this treatment, which the researchers introduced as a powder into the cat’s food, half of the 10 felines whose skin was under insidious attack from the fungus staged remarkable recoveries, offering a potentially promising development that could one day also offer an alternative care for cats and for people.
“The prevalence in South America is 25 to 20 cases per 100,000 people, which is not low,” explained Del Poeta, Distinguished Professor of Microbiology and Immunology. “It affects mostly immunocompromised people and particularly people who have cats or people taking care of infected cats.”
Typically, people get superficial infections, but a person who is severely immunocompromised could have an infection that spreads and becomes fatal.
The work taps into the expertise of Ojima, a Distinguished Professor in the Department of Chemistry. Ojima worked on the structure elucidation, the structure activity relationship and development of efficient synthetic methods for large scale synthesis of the drug.
Recent Stony Brook PhD graduate Ashna Garg contributed to this ongoing effort.
Ojima described the work as “solidly encouraging” and added that the scientists have “even better compounds in the same series for human use” that are more potent and more selective to fungi compared to humans which makes systemic toxicity “very low.”
Del Poeta’s lab has been studying sphingolipids metabolism and signaling in fungal and mammals cells to identify new markers for early diagnosis and microbial enzymes/ molecules essential to cause infections in the attempt to develop new antifungal targets.
To be sure, in the cat research, five out of the 10 cats didn’t complete the study. One of them died, although the cause of death was unknown, and four of the other cats abandoned the study.
Additionally, one of the cats for whom the drug worked showed an elevated level of a liver enzyme, which returned to normal within weeks of the conclusion of the study.
Still, the results were promising and provided encouraging improvements for cats battling an infection that threatened their health.
“I am very pleased with the efficacy of D13 on cats in Brazil,” explained Ojima, adding that it is “a compelling result.”
Additionally, in other preliminary studies, D13 works against various fungal infections, including cryptococcosis, aspergillosis and candidiasis. A new derivative of D13 is more effective for those other infections, the scientists said.
Del Poeta explained that the scientists chose to do the research in Brazil because of the prevalence of sporotrichosis in the area and because he had established collaborations in the country in earlier research.
‘Proud and grateful’
For her part, Garg was thrilled to contribute to research that provided a remedy to a deteriorating condition in an animal some of her friends own as pets.
Cat owners often reacted emotionally when she told them about her work, appreciating the significance of the results.
“I am deeply proud and grateful to have contributed to this work,” said Garg. “Its remarkable effectiveness continues to inspire and motivate me.”
A significant part of her PhD revolved around taking the initial lead compounds and developing second and third generation compounds to enhance their effectiveness and bioavailability.
With three bromine atoms, D13 is an unusual therapeutic treatment.
Bromine is “relatively rare among the top 200 pharmaceuticals,” Garg explained. “Bromine can be toxic or can act as an irritant. Part of my work involved exploring ways to reduce the bromine content” to make the treatment more viable in drug development. The scientists are working to understand why and how this treatment works.
“The exact mechanism of action of D13 is not fully understood yet but we are getting very close,” Garg explained.
With the third generation of D13, the team identified compounds that are highly fungal specific with broad spectrum activity, effectively eradicating 100 percent of the three malignant type of fungi.
“It’s important to note that some first and second generation compounds also demonstrated excellent antifungal activity at very low drug concentrations, even if they did not achieve complete eradication on one of the three fungal strains,” Garg added.
While promising, this study does not indicate a new human treatment will be on the market in the short term.
The scientists are doing toxicology studies and hope a new therapeutic option might be available as soon as five years, Del Poeta estimated.
From Delhi to Stony Brook
Garg, who defended her thesis in December, grew up in Delhi, India, where she pursued her undergraduate studies in Chemistry at Delhi University.
After that, she earned her Master’s in Chemistry at Vellore Institute of Technology in Tamil Nadu, India.
Garg arrived at Stony Brook in 2019 and joined Ojima’s lab in early 2020, just at the start of the pandemic.
“It was indeed a challenging time to start a new position,” Garg acknowledged.
Currently a resident of Poquott, Garg enjoys living on Long Island, where she visits beaches, drives around the area and cooks.
Garg, who attended meetings in the labs of both Professors Ojima and Del Poeta, is grateful for the support of these senior scientists, who were also part of her thesis committee.
Del Poeta described Garg as a “dedicated scientist” with an “impeccable” work ethic.
“Drug synthesis can be very challenging,” Del Poeta described. “She is tirelessly resilient.”
Garg is staying at Stony Brook for another year as a post-doctoral researcher.
Del Poeta is pleased with the productive collaboration he’s had with Ojima, whom he described as “passionate, intellectually stimulating, dedicating, inspiring and hard working.”
If Del Poeta sends an email on Saturday night, Ojima typically replies by Sunday morning.
“It is an honor to collaborate with him,” Del Poeta explained. Ojima’s work “makes these impressive results possible.”
Prev
