Found Animals Spot Light: Becky Cyr and the Soul-Dog

By Siobhan Brier

After Becky Cyr graduated from college, she was living outside of Boston, and every day, on her way to get coffee, she walked past the studio of a stained glass artist. She became friends with the artist and later began walking his dog, Max. She calls Max her “gateway dog.”

So, when Becky moved to California, she started volunteering at the Burbank Animal Shelter. “I loved being around those animals,” she said, but, at the same time, the work opened her eyes to many of the difficult parts of the shelter system. She realized, for example, how reliant shelters are upon selfless volunteers. 

During her undergraduate studies at Tufts University, she knew that she wanted to work in the nonprofit sector as soon as she was able. Her first nonprofit job after college was at an international mental health foundation in Boston, where she worked for over two years before moving to California. 

That experience, combined with her newfound interest in animal sheltering and welfare, primed her for the career that she has had ever since 2012. When Becky saw the chance to work for Michelson Found Animals in their grants program, she jumped on it.

Becky Cyr and Gus

Michelson Prize & Grants

The Need for a Nonsurgical Animal Sterilization Method

Gustavo Barksdale

 

Becky described Gus, full name Gustavo Barksdale, as her “soul-dog.” 

“He was the primary constant in my life for 10 years,” she said, “He saw me through several heartbreaks, accompanied me on hundreds of miles of hikes, and was the sweetest son, husband, roommate, and coworker you could ever hope to have.”

But falling in love with a rescue pup added a new sense of urgency to Becky’s work with Michelson. 

“If the circumstances of Gus’s life had been just slightly different, we might never have met,” Becky explained. “If he had been taken to a kill shelter instead of scooped up by a rescue organization, my soul-dog might not have made it out alive. The healthy, adoptable animals that die in shelters every day are all someone’s potential soul-cats and soul-dogs.”

A Breakthrough

Gus’s Glass

When Becky’s gateway dog, Max, passed away, she was living in California. One day, she got a package from Boston. In it was a small paperweight, a glass orb. She called her friend, the stained glass artist, back in Boston, and he explained that when he made the orb, he had incorporated a swirl of Max’s ashes in it. He told her that he wanted her to always have that small part of the first dog she loved.

Gus passed away in September 2022 after a long life of being adored. Becky points out that Michelson played a large role in allowing her to share so much time with Gus during his lifetime. “Working at Found Animals – first in a dog-friendly office, and then as a permanently remote employee – made it possible for me to be with him for almost every moment of his life,” She said. “How many pet parents get to be in that lucky position?”

After Gus’s passing, Becky had him cremated and then flew to Boston to meet up with her friend, Dan Maher, the stained glass artist.

 

Dan Maher, glass artist and Becky

Dan used some of Gus’s ashes to create seven ethereally beautiful glass orbs, with Gus’s ashes floating inside in a swirl, like a soul. Becky gave four of these orbs to close friends and family who were important fixtures in Gus’s life and kept three for herself.

The glass orbs serve as a visual reminder of the startling impact an animal can have on our lives and why the well-being of animals is so important. They remind us why the time, the grants, the focus, the late nights, and the tears are not misplaced, so long as they help improve the life of even one animal.

On behalf of Michelson Found Animals, thank you, Becky Cyr, for the selfless work you do for animals, and thank you to Gus as well for reminding us why we do the work we do.

Originally published on foundanimals.org.

Journey to a Nonsurgical Sterilant

By Dick Anderson

After nearly a decade in development, a single-dose, nonsurgical sterilant for companion animals has yielded promising results. In a newly published study in Nature Communications, lead author Dr. Lindsey Vansandt, a theriogenologist at the Cincinnati Zoo’s Carl H. Lindner Jr. Family Center for Conservation and Research of Endangered Wildlife, details the findings of a team of scientists working on a new gene therapy treatment with an ovarian hormone to inhibit ovulation and induce durable contraception in the female cat. The work is led by principal investigators Dr. David Pépin, associate professor of surgery at Massachusetts General Hospital, and Dr. Bill Swanson, the Cincinnati Zoo’s director of animal research.

Initially working in the lab of Dr. Patricia K. Donahoe, director of pediatric surgical research laboratories and chief emerita of pediatric surgical services at Massachusetts General Hospital, Pépin was studying the biochemistry of the ovarian Anti-Müllerian hormone (AMH, also known as Müllerian inhibiting substance, or MIS), in the context of ovarian cancer about a decade ago. That’s when a chance discovery in immunosuppressed mice led the researchers to develop a gene therapy strategy to deliver an optimized feline AMH transgene for contraception in the domestic cat. 

“I think it’s a case where we had a solution looking for a problem,” Pépin says. “We had something extremely effective. Maybe it was not so useful for humans. So, we thought, where can we get the most benefit from this discovery—where can this do some good?”

Michelson Prize and Grant nonsurgical sterilant researchers.

Thanks to a colleague at Massachusetts General Hospital, Pépin and his team learned about the Michelson Prize & Grants in Reproductive Biology, a $75-million initiative launched by the Michelson Found Animals Foundation in 2008 to create a nonsurgical sterilant for cats and dogs to eliminate shelter euthanasia of healthy, adoptable companion animals and reduce populations of free-roaming cats and dogs.  

“In many parts of the United States and around the world, you’ll see dogs just wandering down the street, and invariably, they are not neutered or spayed,” says Dr. Gary K. Michelson, founder and co-chair of Michelson Philanthropies, which hosts the Michelson Prize & Grants program. “It’s very expensive and logistically difficult to have these animals undergo surgeries that require anesthesia. Even in America, many families don’t have the resources to have their animals spayed and neutered.”

According to the Best Friends Animal Society, about 4.4 million cats and dogs entered U.S. shelters in 2022. Many of those result from unplanned litters, and millions more cats are living outside with inadequate care. If there was a means of dramatically reducing unwanted reproduction, Dr. Michelson reasoned, “Every municipal animal shelter could successfully find a live outcome for every healthy dog and cat. That is the holy grail.”

When the Michelson Prize & Grants program was first announced in 2008, “Dr. Michelson stipulated that he wanted a sterilant that didn’t require surgery, something that would suppress hormonal activity in dogs and cats,” Swanson says.

Pointing toward the potential breakthrough of a sterilant for female cats, he notes, “The main metric we’re looking at is reproduction: Are they breeding and reproducing? And those data are very solid and exciting. We’re also monitoring reproductive hormones in these cats and looking at their behavior.  The ultimate goal is keeping cats from reproducing. And we’ve shown clearly that we can do that safely and effectively, with absolutely no adverse effects observed in any of the treated cats, all of which are either eligible for adoption or already in loving adoptive homes.”

“The results in the cats have been amazing.” Donahoe says. “The care in the design and the delivery and the interpretation of this has been really outstanding. I think this paper will make a real mark on the field of reproduction.”

Over the last 15 years, the Michelson Prize & Grants program has funded 41 projects totaling more than $19 million in committed funds for this specific area of research. “We have figured out a lot of things that don’t work, which in itself is progress,” says Becky Cyr, program manager of the Michelson Prize & Grants program since 2012. “When this program started, our scientific advisory board was interested in hearing any idea with scientific merit. And we have funded a broad range of approaches over the years.”

“There’s not a lot of funding in this space to begin with,” says Dr. Thomas Conlon, chief scientific officer of Michelson Philanthropies and Michelson Found Animals. “The work that we have funded, the peer-reviewed publications that grantees have put out, and the presentations that they’ve given at conferences are adding to the scientific literature in this area of research. That wouldn’t be occurring without Dr. Michelson’s funding.”

The road to a nonsurgical sterilant can be traced back to Dr. Michelson founding the Michelson Found Animals Foundation in the wake of Hurricane Katrina in 2005. The foundation’s success in developing a national microchipping network caught the eye of Joyce Briggs, president of the nascent Alliance for Contraception in Cats and Dogs (ACC&D), who approached Dr. Michelson about funding a prize to advance the development of nonsurgical sterilant for cats and dogs. 

 

Cincinnati Zoo cats, nonsurgical sterilant funded study
Cincinnati Zoo cats, Bernie and Fennec.

“Cats are really good at reproducing,” says Briggs, who began volunteering in animal shelters as a teenager. “They are predominantly induced ovulators, which means that the act of mating actually causes ovulation. They continually cycle until they get pregnant. It is very challenging to interfere with that.” (Dogs are very different from cats, she notes: They usually cycle once or twice a year.) “We still have an overpopulation issue with cats in many areas of this country. And in almost every area, there are issues with free-roaming cats that are very hard to get ahead of.”

In 1999, Briggs became executive director of PetSmart Charities, the nonprofit arm of the world’s largest pet supplies retailer. Within a couple of years, Briggs started to see a trickle of applications from scientists interested in pursuing nonsurgical spay/neuter technologies. “I did not have the scientific background to evaluate the potential of these technologies, but as a funder, I desperately wanted our spay neuter grants to better address the huge need. I was very interested in advancing the technologies,” she says.

Around 2000, Briggs was a founding member of Animal Grantmakers, which pulled together a “summit of sorts” of a couple of dozen grantmakers and scientists to foster a greater understanding of the potential of nonsurgical sterilization. At that same summit, Briggs met three scientists from the Auburn University and Virginia Tech veterinary schools who had just formed the Alliance for Contraception in Cats and Dogs (ACC&D), which bridges the animal welfare, scientific, veterinary, and pharmaceutical communities with the shared goal of expanding options for controlling feline and canine reproduction.

After Briggs became president of the nonprofit ACC&D in 2006, she and her board of directors began to actively seek out funding toward the development of science-based nonsurgical spay/neuter procedures. Before long, someone suggested that she should consider approaching Dr. Michelson with the idea for the prize, and it made sense to Briggs: “Gary’s scientifically minded; he’s from the medical establishment; and he believes in innovation around solving things,” she recalls thinking. “What better than a scientifically-based medical intervention that could be a game changer for this field? It was a really nice match for him.”

Dr. Michelson was receptive to Briggs’ “bold ask” of creating a $10 million prize, “but it wasn’t audacious enough,” he recalls. “It needed a bigger prize.” So, he upped the ante to $25 million, and responded to the ACC&D Board’s follow-up request that he also provide grant funds,  adding $50 million in grant money to underwrite the research. “In essence, there was zero research going on in this field,” he says. “Unless we were willing to fund the research ourselves, nothing would happen.”

When the Michelson Prize & Grants program was announced, it made headlines nationally. “Saturday Night Live said the cats and dogs got together and put up $75 million to have me fixed,” he recalls with a laugh. “In the beginning, we were funding lots of divergent hypotheses about how you might achieve this.”

Soon after Dr. Shirley Johnston was named Michelson Found Animals’ director of scientific research in 2009 (a position she would hold until 2016), one of the first things she did was form MFA’s scientific advisory board, which has been the brain trust and driving force of the Michelson Prize & Grants program from day one. “In the first few years, we processed tons of letters of intent and grant applications,” Cyr says. 

David Pépin went through the traditional channels of submitting a letter of intent and grant application in 2014. “He was doing some research at the time where a side effect of a treatment that he was working on happened to cause infertility in rodents—and he thought there might be other applications for this,” Cyr says.

“I joined Pat Donahoe’s lab as a postdoc initially to work on ovarian cancer and the biochemistry of AMH—how to make it and how to use it in the context of ovarian cancer,” recalls Pépin. He did his Ph.D. at the University of Ottawa studying ovarian function—how the ovary works—and folliculogenesis, which is the growth of follicles that leads to ovulation. 

For Pat Donahoe, the pet overpopulation problem was made “very evident” at the 2014 Winter Olympics in Sochi, Russia, where hundreds of stray dogs were culled before the games, igniting a global outrage. “When the athletes arrived in the Olympic Village, they were surrounded by feral cats and many feral dogs,” she recalls. “It became quite obvious that this problem is a scale of magnitude that we don’t even conceive of.”

“As a pediatric surgeon, I was extremely interested in reproduction and the birth defects that occur with reproduction,” says Donahoe, who has worked her entire career at the Massachusetts General Hospital in Harvard Medical School. She was spending a lot of time reconstructing children who were born with intersex abnormalities and closely followed the AMH work being done by Dr. Jean Wilson, an internationally recognized endocrinologist and professor of internal medicine at UT Southwestern Medical Center.

“We were working on AMH because it had this tremendous effect in the male embryo of wiping out the Müllerian ducts, which would otherwise give rise to the female reproductive system,” Donahoe explains. “We had two concepts in mind. One is that this was a very powerful inhibitor. And if it’s an inhibitor, could we use it to inhibit tumors of the Müllerian ducts and the most prominent of which is ovarian cancer and all ovarian cancers recapitulate the developmental program or the development of the Müllerian ducts.  So, we started very slowly looking at designing a bioassay for AMH, then learning to purify it, then cloning the gene for it, which we did with Biogen Corporation.” 

Cincinnati Zoo cats, nonsurgical sterilant funded study

It was at that stage that Pépin came to the lab as a postdoc. “He was a godsend at that point because we had cloned the gene, and yet the purification schemes were very, very difficult,” Donahoe says. “David worked on changing the constructs to make them more potent and to improve our ability to sequence and purify them. And David was able to change the construct, change the gene so it was easier to produce and cleaner and almost 100 percent purified.”

“Because of my training on ovarian physiology, I was also interested in looking at what the effect on the ovary was, and that’s how we made that discovery,” Pépin says. “At the outset, we were trying to treat ovarian cancer. It was already known that AMH was an ovarian hormone that may regulate ovarian follicles. But what we found is that it was much more potent than anticipated and actually completely shut down the ovary.”

As they thought about the applications for this discovery, “The most obvious one, if you’re shutting down ovarian function, is contraception, and we were looking at different funding opportunities that pursue that,” Pépin continues. Caroline Coletti, program manager at Massachusetts General Hospital, found the Michelson Prize website and showed it to Pépin. 

“I thought, ‘Wow, that’s very interesting,’” he recalls. As part of the grant, what we wanted to do is clone both the dog and cat AMH genes. So, we needed to identify people that would help us with both of these.” Pépin reached out to Dr. Guangping Gao, director of Horae Gene Therapy Center and Viral Vector Core at the University of Massachusetts and maker of all the vectors for these studies, and they submitted a proposal together to the Michelson Prize & Grants program.

Our contact with Guangping Gao was serendipitous and really terrific because they had the knowhow of making these adeno-associated viruses and scaling them up,” Donahoe says. “They’ve been very flexible and a dream to work with.”

The maturation of the gene therapy field has been key to the team’s research, Swanson notes. “Twenty years ago, we probably wouldn’t be proposing to do anything like this, even though gene therapy was active then.” (On the subject of gene therapy, he adds, “We’re not genetically modifying these individual animals. This is producing a protein over the life of the animal which will shut down reproduction. It has no effect on the animal’s DNA.”)

Dating back to his work with the Austin Humane Society in the early 1980s, Swanson has been wrestling with the overpopulation of dogs and cats in the United States. “Most of my career has been focused on trying to conserve endangered cat populations—kind of the opposite of keeping them from breeding,” says Swanson, who joined the Cincinnati Zoo in 1997. “We want these endangered cats to breed, and we want to be able to keep their populations viable.”

Along with completing his Ph.D. research at Louisiana State University focused on domestic cat reproduction, Swanson worked at the Smithsonian Institution’s National Zoo and Conservation Biology Institute, which used the domestic cat as a reproductive research model for endangered cat populations. His mentor at the Smithsonian, wildlife biologist Dr. David Wildt, recruited him to the scientific advisory board for the Michelson Prize & Grants program about a decade ago. 

Swanson first met Donahoe and Pépin at a meeting in California for the Michelson Found Animals Foundation. “I hadn’t been on the board that long at that point, and they had come out for a grantee meeting,” he recalls. “The work David and Pat were doing and proposed to do looked promising based on the mouse data.”

Over time, Swanson’s role evolved from being an adviser to a collaborator on Pépin and Donahoe’s project. “They needed someone with expertise on cat reproduction to take this from the mouse model to the cat as an endpoint,” he says of Pépin and Donahoe. “Because we study cats as a model for endangered cats in my facility at the zoo, we work with them all the time. It was a really good fit with the project that David and Pat were developing to see if this inhibitory protein-anti-Müllerian hormone-would work in inhibiting reproduction in domestic cats.”

“Our colony has about 50 domestic cats now—we’ve had as many as 100—and most of those are here because of the project that we’re doing with David and Pat,” he adds. (In November 2015, the Swanson lab worked on a study sponsored by ACC&D to evaluate the potential of a vaccine named GonaCon as a long-term contraceptive for female cats.) We’re in our third study now with David and Pat, and we have plans for more studies as we go on. The results of the first two studies were impactful and promising for what we’re trying to achieve.”

As a conservation biologist and a veterinarian, “I look at this as an animal welfare issue,” Swanson says. “Because these stray dogs and cats live outdoors, they can have pretty traumatic lives. A lot of these animals get infectious diseases or get hit by automobiles.”

In addition, “Cat predation is a major source of mortality in wild birds,” notes Jenny Gainer, Swanson’s colleague and curator of birds and African animals at the Cincinnati Zoo. “Controlling and reducing the population of free-roaming cats will make a major difference for declining songbird populations.”

When would a sterilant like this actually be available for use? “Just like any drug for humans, it has to go through regulatory approval for use in companion animals,” Pépin says. “So that means doing clinical trials. That means going through the FDA, and that’s a multi-year process. In some ways, we’re lucky that we can do experiments in the target species, which is not usually the case in humans,” he adds. “We already have data on cats. So now it’s just a matter of demonstrating safety, proving effectiveness in a larger population of female cats, and developing a cost-effective manufacturing process.”

Michelson Found Animals is scheduled to meet with the Center for Veterinary Medicine at the FDA to begin the regulatory approval process. “We’re going to discuss our pivotal study plans for the next few years,” Conlon says. “The FDA will provide guidance on whether they agree with our plan as well as review our study designs to establish safety and efficacy. We will also have to develop robust quality manufacturing and those processes will be reviewed by the FDA as well.” Any approval of a nonsurgical sterilant, domestically or abroad, is “years down the road,” he adds.

As the work progressed, Pépin is running a large group now as an independent investigator at the Harvard Medical School (where he was promoted to associate professor in 2021). “I have my own lab now that studies the ovary first and foremost,” he says. 

Without the support of Michelson Found Animals, Pépin adds, “I guarantee this work would have never happened. Our interaction started as a more typical funder/grantee relationship. But as we’re getting closer to a product and real-life application it’s evolved into a different role. We’re in constant contact and more like a team working on it with a common objective.”

“I don’t think Dr. Michelson has ever denied any of our requests for funding,” adds Donahoe. “They’re very particular—they want everything spelled out in detail before they release their funds—but that’s our mantra as well.”

The funding from Dr. Michelson has been transformational,” Swanson says. “There really wasn’t much being done in the field of dog and cat contraception until this funding source became available. Universities aren’t going to be doing the research if they can’t get the money to do it. Before the Michelson Prize & Grants Program, that probably would’ve been a dead end.”

Pépin discussed the study’s findings at the American Society of Gene & Cell Therapy’s 26th annual meeting in Los Angeles on May 20 in a talk titled Use of a Gene Delivery Approach for Single Dose Lifetime Sterility in Female Cats: An Alternative to Spay. Pépin’s presentation was delivered during a four-hour symposium on gene therapies for companion animal health that was chaired by Conlon.

“This presentation and now the subsequent publication represents the breakthrough moment where we’re finally able to talk about all the Pépin data after having the intellectual property all locked up,” Conlon says. Any resulting product “has to be something that is cost effective to produce,” Dr. Michelson adds. “If it’s so expensive that we can’t produce it, then we really haven’t succeeded. We have to have a product that’s usable.”

In deploying the sterilant as a business model, the challenge may well be finding an intersection between those who can afford it and getting it at the lowest cost to the most in need. ACC&D has done some market analysis for Dr. Michelson on what the market size looks like for these target audiences. “While the hope is that this can be provided as affordably as possible to charitable initiatives for homeless animals and for people who have very little income for veterinary care, this is also a benefit for pet owners who would prefer something less invasive than surgery,” Briggs says. The business model is important to us at ACC&D because a new tool is only as good as how well we’re able to deploy it in the field.”

“Having worked on spay/neuter for 30 years now, this is a legacy I want to leave behind,” she adds. The irony that a trio of surgeons and surgery researchers —Donahoe and Pépin, with the support of Dr. Michelson—may have succeeded in creating a nonsurgical sterilant is not lost on her: “I love that.”

“If everything that we’re doing fails—and I don’t think we’ll fail—there will always be another technology to be explored until we achieve our goal,” Dr. Michelson says. And if the prize criteria for either the cat or dog is met, he adds, “I’d be more than happy to write that check.”

Michelson Prize & Grants-Funded Study Published in Nature Communications, Offers Potential Alternative to Surgical Spaying

Gene Therapy Produces Long-term Contraception in Female Domestic Cats

Michelson Prize & Grants, a program of The Michelson Found Animals Foundation, is offering a $25-million prize to scientists to develop a permanent, “single-treatment,” nonsurgical sterilization method for male and female cats and dogs.

Currently, there are no contraceptives capable of producing permanent sterilization in companion animals. For the first time, researchers at Massachusetts General Hospital (MGH) and their collaborators have demonstrated that a single injectable dose of a gene therapy-based treatment can induce long-term contraception in female domestic cats, potentially providing a safe and effective alternative to surgical spaying. The research is published in the latest issue of Nature Communications.

“Although surgical sterilization has been an effective tool for controlling unwanted pregnancies in cats, it is both costly and labor intensive. A solution that only requires a single injection could potentially make a significant impact on the overpopulation of cats.  We engineered a viral vector to deliver a feline transgene that increases the amount of a natural hormone to prevent ovulation,” says senior author David Pépin, PhD, Associate Molecular Biologist in Surgery at MGH and Associate Professor of Surgery at Harvard Medical School. “The gene therapy is delivered in a single injection and thus less invasive and more scalable than spaying.” 

The team of investigators at MGH, the Center for Conservation and Research of Endangered Wildlife (CREW) at the Cincinnati Zoo and Botanical Garden, and the Horae Gene Therapy Center at the University of Massachusetts Medical School received funding from The Michelson Found Animals Foundation in support of this research.

“A nonsurgical sterilant for community and companion animals is long overdue and will transform animal welfare,” said Gary K. Michelson, M.D., founder and co-chair of Michelson Philanthropies and the Michelson Found Animals Foundation. “This breakthrough discovery is a major milestone in our quest to provide pet owners with an alternative to surgical spay and neuter.”

Click Here to Read the Full Publication from Nature Communications

 

Michelson Grants Research Findings To Date: A Look Back on Seven Years of Grant Funding

It’s hard to believe that the time has passed so quickly, but this October marked the 7th anniversary of the Michelson Prize & Grants program! As we celebrate this milestone, we’d like to share with our readers the important progress that has been made since then in the field of nonsurgical sterilization. Through the tireless efforts of our grantees and their research teams, the dedication of our diverse and talented Scientific Advisory Board, and the generosity of our funder, Dr. Gary Michelson, we have made significant steps toward the development of a noninvasive spay/neuter method for companion animals and we hope that you will share our enthusiasm after reading this update.

A major goal of the Found Animals Foundation is to develop a single-dose, permanent (10-20 year), nonsurgical sterilant that renders male and female dogs and cats infertile. Our desired product must induce sterility as well as suppress reproductive hormones and behavior (such as estrus, matings) in treated animals. If made available to the ~3500 shelters in the U.S.A., such a sterilant could guarantee that every animal adopted would be incapable of reproducing, thereby eliminating the birth of unwanted litters that ultimately end up back in the shelter system. Nationally and internationally, such a product could also be administered by paraprofessionals to feral and free-roaming dog and cat colonies. We envision that this nonsurgical sterilant will be a total game-changer for the care and management of shelter, feral, and free-roaming dogs and cats all over the world and could eventually eliminate the euthanasia of shelter animals altogether.

Thirty-five Michelson Grants in Reproductive Biology, totaling about $15 million in committed research funds, have been awarded to scientists around the world since 2009 to perform research leading to the development of this sterilant. Grants have been awarded to scientists in the U.S.A., Canada, Argentina, Australia, the Netherlands, New Zealand, and Scotland.

To date, scientists performing this research have targeted one of three sites in the body that are essential for reproduction. These are:

  • the hypothalamus, the part of the brain that contains cells which initiate reproduction by secreting the hormones kisspeptin and gonadotropin releasing hormone (GnRH);
  • the pituitary gland, a pea-sized organ at the base of the brain that responds to secretion of GnRH by secreting luteinizing hormone (LH) and follicle stimulating hormone (FSH); and
  • the reproductive organs in the abdomen (ovaries) or scrotum (testes) that respond to LH and FSH by producing eggs, sperm, and hormones such as estrogen and testosterone that cause reproductive behaviors.

Scientists have endeavored to block normal reproductive function at these sites using one or more of the approaches described below. Some of their findings are bulleted under each approach.

Gene Silencing

Genes in all body cells encode for, or express, proteins/peptides that are active building blocks or enzymes. In the gene silencing approach, scientists inject an inactive virus (either a lentivirus or adeno-associated virus) intravenously that has a nucleic acid fragment inserted that is an exact mirror image of the gene that they want to silence. The mirror image (interference RNA) attaches to this gene and prevents its ability to express its protein. One of the first Michelson Grants awarded was to silence genes in cells of the hypothalamus that express kisspeptin and neurokinin B (NKB). These proteins/peptides normally induce GnRH secretion.

  • A gene silencing construct to silence kisspeptin and NKB genes in the hypothalamus disrupted female rat estrous cycles but did not completely ablate fertility; studies are now underway to enhance specific delivery of this construct to the hypothalamus in high concentrations.
  • Genes that express dog and cat kisspeptin and NKB in the hypothalamus were cloned and respective genomic structures were determined. It was discovered that the dog kiss1 gene is the most divergent of all mammalian species known.
  • Genes expressing kisspeptin and the kisspeptin receptor in the hypothalamus were cloned in the dog. Investigators demonstrated that estrous cycle stage influences kisspeptin signaling in dogs.
  • Silencing of the genes that express androgen receptor proteins in the testes induced long-term spermatogenic arrest and sterility in male mice.
  • Dog testes (seminiferous tubules) were shown to express functional piRNA binding proteins called “PIWI proteins” that are essential to spermatogenesis; in normal reproduction, these are critical mediators of egg and sperm maturation. They could be a good target to silence in efforts to induce sterility.

Gene Therapy

Gene therapy also uses a lentivirus or adeno-associated virus, but the nucleic acid fragment inserted is a functional gene that expresses a protein. This approach is used to treat a variety of human diseases and has been able to express a blood clotting factor for more than 10 years in dogs with hemophilia. The Foundation has approved studies to use gene therapy to express antibodies to GnRH, to express gonadotropin inhibiting hormone (GnIH), and to express Mullerian Inhibiting Substance (MIS).

  • Gene therapy delivering antibodies to GnRH causes sterility in rodents by blocking hypothalamic GnRH.
  • Human GnIH inhibits secretion of reproductive steroid hormones in cat ovarian tissue.

Immunocontraception

Immunocontraception describes induction of antibodies to essential reproductive hormones so that the antibodies bind to and block these essential reproductive elements. The mechanism is similar to that of inducing antibodies by injecting inactivated bacteria or viruses that cause disease, except that immunocontraception relies on creating antibodies to “self” antigens. Dogs and cats have been immunized against GnRH for decades and shown to be infertile for 1 to 3 years after a single administration. Work funded by our program is in progress to provide slow or repeated release of vaccines against GnRH in the hypothalamus, the GnRH receptor in the pituitary, or other reproductive proteins.

  • Administration of a GnRH vaccine on a subcutaneous three-dimensional adjuvant matrix that mimics the body’s response to infection resulted in recruitment and activation of (antigen presenting) dendritic cells and long-term persistence of antibodies to GnRH secreted by the hypothalamus.
  • A study is in progress in mice to release GnRH vaccine from a slow-release subcutaneous implant “smart” device that releases the antigen when circulating antibodies to GnRH fall.

Targeted Delivery of Cytotoxins

Some scientists are trying to destroy cells in one of the three sites that are essential to reproduction by delivering toxins exclusively to the target cell, and not to other body tissues. This methodology also is used to destroy cancer cells in patients receiving chemotherapy.

  • Investigators discovered that the gene sequence expressing the kisspeptin receptor protein (reported in public databases) in rat hypothalamic cells was incorrect and nonfunctional. The correct sequence was determined and confirmed, and the National Center for Biotechnology Information corrected the database based on that funded research.
  • In a study of attempted toxin ablation of pituitary cells secreting LH and FSH, our investigators have found that gonadotropes are resistant to toxin ablation. Others have demonstrated that toxin degradation within structures called “endosomes” may be limiting efficacy. In fact, it has been estimated that only about 1 in 10,000 internalized toxin (ribosome inactivating proteins) escape endosomal destruction. A research team of Michelson Grant awardees is now adding “endosome escape” substances to the toxin ablation constructs to enhance efficacy.
  • Administration of a GnRH agonist implant (deslorelin) to kittens within 24 hours of birth blocked receptors on pituitary cells from access to native GnRH. This resulted in delayed onset of puberty, to 42-91 weeks of age, compared to normal onset of puberty at 15.5 +/- 1.7 weeks in control kittens. Investigators hypothesize that neonatal use of a higher dose of deslorelin might prevent puberty altogether. A similar study in dogs is ongoing.
  • Scientists discovered that Sertoli cells in the testes require a different mechanism of inducing cell death than do the primordial germ cells that produce sperm because of different phagocytic/endocytic functions.
  • Administration of (toxic) reactive oxygen species linked to FSH that target the ovaries and testes caused germ cell death in mice.

Our grantees’ work is frequently published in peer-reviewed journals and presented at international conferences. If you would like to learn more about any of our funded projects, be sure to check out the full Michelson Grants Research Findings listing on our website!

Three New Members Join the MPG Scientific Advisory Board

The Scientific Advisory Board of the Michelson Prize & Grants in Reproductive Biology has gained three new members: Drs. Thomas Conlon, Kevin Morris, and Marcel Van Duin.

Thomas Conlon, PhD, is an Assistant Professor in Pediatrics and the Director of the Powell Gene Therapy Center Toxicology Core at the University of Florida. As the Director of the Toxicology Core, Dr. Conlon facilitates efficient, cost-effective, and rigorous preclinical testing of gene therapy vectors, with a special emphasis on recombinant adeno-associated virus (rAAV) vectors. Dr. Conlon has also collaborated with the University of Florida College of Veterinary Medicine to identify and treat two types of cardiac problems experienced in dogs.

Kevin Morris, PhD, has been actively involved in cancer research in both academic and biotechnology environments for over 20 years. He has served as the Principal Investigator on a wide range of studies in animal sheltering, pet overpopulation, and the field of human-animal interaction. Dr. Morris is currently serving as the Co-Principal Investigator on the American Humane Association’s Canines and Childhood Cancer Study and is also a member of the Board of Directors of the Alliance for Contraception in Cats and Dogs (ACC&D).

Marcel Van Duin, PhD, is the Senior Director, Therapeutic Area Head Reproductive Health Research at the Ferring Research Institute in San Diego, CA. Dr. Van Duin has over 25 years’ experience in various leadership positions in the pharmaceutical industry, including as the Head of Pharmacology at Organon Research in Newhouse, Scotland, where he was responsible for all pharmacological research in the areas of reproductive biology, oncology, immunology, and toxicology, as well as the animal research facilities.

Says Dr. Gary Michelson, the founder of the Found Animals Foundation, “I am delighted to welcome Drs. Conlon, Morris and Van Duin to the Scientific Advisory Board. Their expertise in gene therapy, molecular biology and reproductive biology strengthen our Board.”

These newest members join nineteen other elite experts in the fields of reproductive biology, neuroscience, veterinary medicine, immunology, and toxicology on the Scientific Advisory Board. As a group, they review grant proposals and guide the Michelson Prize & Grants program toward our goal of finding a nonsurgical sterilant for use in male and female cats and dogs.

We are very excited to welcome these new board members to the fold and look forward to the exciting new projects that the Board will be reviewing in 2015!

USC Michelson Center for Convergent Bioscience Breaks Ground

A new era in medical research began in October, as the USC Michelson Center for Convergent Bioscience broke ground on the University Park Campus of the University of Southern California (USC).

The new building, made possible by a $50 million gift from Dr. Gary Michelson, the founder of the Found Animals Foundation, and his wife Alya Michelson, will add 190,000 square feet to the campus and will accommodate about 25 to 30 investigators working in collaborative, shared lab spaces. In addition to the flexible labs, the building will also hold a Center for Electron Microscopy and Analysis, a nanofabrication facility, and a suite of microscopy imaging technology – all to be outfitted with top-of-line tools and equipment. The Center is expected to be completed in 2017.

The creation of the USC Michelson Center marks a new collaboration between the USC Dornsife College of Letters, Arts and Sciences and the USC Viterbi School of Engineering. Says Dr. Michelson, “USC is well-known for producing entrepreneurs in a wide array of disciplines, and the USC Michelson Center will now help leverage the university’s network of scientists and engineers to tackle challenges in health, biomedicine, and many related fields.” Further, Dr. Michelson predicted that the Los Angeles area will soon become an epicenter for biomedical research.

The Michelson Prize & Grants team is especially excited about the USC Michelson Center, as its promise of integrative research coincides with our approaches in reproductive biology, toxicology, immunology, and many other disciplines to find a single-dose, nonsurgical sterilant for cats and dogs. We look forward to hearing more from the Center!

MPG Scientific Advisory Board Visits the Cincinnati Zoo & Botanical Garden

The Scientific Advisory Board of the Michelson Prize & Grants in Reproductive Biology program recently held their final meeting of the year, but this was no typical board meeting – this month the Board found themselves at the Cincinnati Zoo & Botanical Garden spending time with Bactrian camels, a cheetah, and the only Sumatran rhino in captivity in Northern America. They even got up-close and personal with several free-roaming peacocks (who tend to think they run the Zoo)!

This exciting trip was made possible through the generous hospitality of Dr. Bill Swanson, the Director of Animal Research at the Zoo’s Center for Conservation and Research of Endangered Wildlife (CREW), and one of MPG’s Scientific Advisory Board members. Not only did Dr. Swanson volunteer to host the Board meeting, but he also graciously gave the Board a “backstage tour” of the Zoo the following day.

In addition to holding this meeting in a new and exciting venue, the meeting format this time around was also very different for our Board. Rather than evaluate new proposals for funding consideration, the Board took a close look at the 33 projects that it has approved over the past 5 years in order to draw important conclusions about which approaches and targets appear to be the most promising, and to develop clear ideas about where the program should head in the future. While the Board is very excited about all of the Michelson Grant research findings generated since it awarded its first grant in 2009, strategic planning exercises like this will ensure that we are seeking out and funding projects that are most likely to quickly help us reach our goal of developing a nonsurgical sterilant for cats and dogs.

On the day following our meeting, Dr. Swanson treated the Board to a tour of the Cincinnati Zoo & Botanical Garden, which included stops along the way at CREW’s facilities, the Zoo’s veterinary hospital, and meet-and-greets with Humphrey and Jack (Bactrian camels), Harapan (Sumatran rhino), and Savanna (cheetah), one of the Cat Ambassadors of the Zoo.

What the Board found was that Jack (Humphrey’s son) loved to have his picture taken, Harapan enjoys a good nose rub, and Savanna purrs just like any other house cat (although much louder).

The Board also learned about the crucial conservation work CREW is performing on a daily basis. Through advanced animal research and plant research, CREW is working to secure a positive future for endangered species. CREW’s current Signature Conservation Projects include exceptional plants, rhinos, small cats, and polar bears.

The next MPG Board meeting will take place in February 2015 and, although it won’t include visits with endangered species or exotic animals, it will bring the Board another opportunity to review new and innovative proposals in the search for a single-dose, nonsurgical sterilization method for cats and dogs. The whole Michelson Prize & Grants team looks forward to it!

Michelson Prize & Grants Featured on NPR

The Michelson Prize & Grants in Reproductive Biology was recently featured on 89.3 KPCC-FM, the Southern California National Public Radio affiliate, to discuss the success of the program to date in the search for a single-dose, permanent, nonsurgical sterilization method for cats and dogs.

The story features insight into the Michelson Prize & Grants program from both Aimee Gilbreath, Executive Director of the Found Animals Foundation, as well as Dr. R. Scott Struthers, the President and Chief Scientific Officer of Crinetics Pharmaceuticals and a current Michelson Grantee.

The story comes at an exciting time for the Michelson Prize & Grants program, as two more grants get underway. Cristina Gobello, MV, DVM, Small Animal Specialist, DECAR, a Professor and Investigator at the Laboratory of Reproductive Physiology at the National University of La Plata and the National Research Council of Argentina, recently began her second Michelson Grant-funded project, a four-year grant totaling $132,576 titled, “Prepubetal administration of a long term release GnRH agonist in domestic dogs: A Pilot Study.” Dr. Gobello recently completed another three-year project funded by the Michelson Grants totaling $91,638.

Additionally, Sergio Ojeda, DVM, a Senior Scientist in the Division of Neuroscience at the Oregon National Primate Research Center will begin a two-year grant totaling $471,487 in October for his project, “Engineering viral vectors to target the cat hypothalamus with sterilizing molecules.”

As the sole funders of the Michelson Prize & Grants program, Dr. Gary K. Michelson and Alya Michelson are proud of the continued commitment that researchers such as Drs. Struthers, Gobello, and Ojeda are making towards finding a single-dose, permanent, nonsurgical sterilant for both cats and dogs. Says Dr. Michelson, “I am excited by the progress we’ve made in the nearly six years since we launched this program. We congratulate Drs. Gobello and Ojeda on their newly approved grants and thank Jed Kim and KPCC for their thoughtful coverage.”

For more information about all Michelson grantees, visit our Current Grantee Profiles and Research Findings pages.

New Advisors Appointed to Scientific Board

The Michelson Prize & Grants welcomes two new members to the Scientific Advisory Board: Dr. Margaret Barr and Dr. Amy Ross.

Margaret Barr, DVM, PhD is a Professor of Virology and Immunology at the College of Veterinary Medicine in Western University of Health Sciences. Her research includes investigating the molecular epidemiology of canine parvovirus and rickettsial agents in Southern California. Dr. Barr also serves as project director for the Snow Leopard Functional Genomics Initiative, which studies the immunogenetics of captive and wild snow leopards.

Amy Ross, PhD, is the President of the Board of Governors of the University of Southern California Alumni Association. Her background is in Experimental Pathology, which led to more than 25 years of experience in the bone marrow transplantation and cancer diagnostics field. Dr. Ross’ research focused on the detection of tumor cells in the circulation of breast cancer patients as a means of targeting early relapse.

Dr. Barr and Dr. Ross will join the twenty other world-class advisors on the Board dedicated to guiding the MPG program toward the goal of a single-dose nonsurgical sterilant. To read more about our advisors and their areas of expertise, please visit our Board Bios page.

The Michelson Prize & Grants Goes to Europe

In February, Michelson Prize & Grants Program Manager Becky Cyr had the incredible opportunity to attend the 11th International Symposium on GnRH in Salzburg, Austria. The three-day program, which attracted 170 participants from 35 different countries, was packed with sessions on the hypothalamic-pituitary-gonadal axis in cancer and reproduction. This was an important meeting for the Michelson Prize & Grants program, because every attendee was studying an aspect of gonadotropin-releasing hormone (GnRH), the master control hormone for reproduction. GnRH has long been a target for a nonsurgical sterilization method in animals, because it is evolutionarily conserved among different species and both males and females. This means that if someone can engineer a vaccine to immunize against GnRH for the lifetime of an animal, or deliver a cytotoxin to target and permanently kill or inhibit GnRH neurons, we could have a contender for the Michelson Prize. About 1/3 of our funded projects involve targeting GnRH neurons.

Because this meeting’s attendee base was such a receptive audience for our goal of developing a permanent, nonsurgical sterilant for companion animals, the Michelson Prize & Grants program organized an evening session on the second day of the conference, during which four Michelson Grantees presented their research approaches. The session began with a brief overview of the MPG program’s background and goals, our international research grants, and prize philanthropy model. Then, Drs. Auke Schaefers-Okkens (Utrecht University), Scott Struthers (Crinetics Pharmaceuticals), Doug Jones (Iowa State University), and Greg Dissen (Oregon Health & Sciences University) presented specific approaches that they are currently using with Michelson Grant funding to immunize against, ablate, or inhibit GnRH neurons. The session was very well attended, and attendees had stimulating questions for our grantees.

The GnRH symposium was a great success, and we are proud to have been a sponsor of such an important meeting. We’re looking forward to a busy conference season this year, with the upcoming Society of Toxicology Annual Meeting & ToxExpo on March 23-27 in Phoenix, AZ, and Experimental Biology on April 26-30 in San Diego, CA. We hope to see you there!

New Michelson Prize & Grants Website Launches on World Spay Day

February might be our favorite month out of the whole year. Not only is it Spay/Neuter Awareness Month, but today – February 25, 2014 – is also the 20th anniversary of World Spay Day.

If you’re reading this blog and you’re already a fan of the Michelson Prize & Grants program, the importance of spay/neuter is certainly not lost on you. Not only does it bring about specific health and behavioral advantages, like eliminating or reducing your pet’s chances of developing certain types of cancer and stopping your pet’s hormonally influenced reproductive behaviors, it also prevents the birth of unwanted litters. With an estimated 6-8 million cats and dogs entering animal shelters in the United States each year, spaying and neutering (also called “sterilizing”) our companion animals continues to be of utmost importance.

To celebrate World Spay Day’s 20th anniversary, we are very excited to announce the official launch of our new Michelson Prize & Grants website. We hope that you’ll take a few minutes of your day to browse through our new Frequently Asked Questions feature to learn more about our program, scroll through our easier to navigate Research Findings to read important conclusions drawn from completed Michelson Grant-funded projects, and review our Michelson Grant Application page for clarified instructions on how to apply for a research grant.

This year also marks the 5th anniversary of the Michelson Prize & Grants program. We continue to seek out new researchers who can join us in our mission to develop a permanent, single-dose, nonsurgical sterilant for male and female cats and dogs, and are very enthusiastic about the 30+ projects we have approved for funding to date through the generous contributions of Dr. Gary K. Michelson and Alya Michelson.

Dr. Gary K. Michelson Donates $50 Million to New USC Bioscience Center

Dr. Gary Michelson, founder of the Michelson Prize & Grants program, has donated $50 million to the University of Southern California for the construction of a new bioscience research building on campus.

The USC Michelson Center for Convergent Bioscience will bring together researchers of multiple fields from within the USC Dornsife College of Letters, Arts and Sciences and the USC Viterbi School of Engineering. USC News stated that the goal of the 190,000-square-foot center is “to turn the biological sciences into a quantitative and predictive science, fast-tracking the detection and cure of diseases.” With building completion expected three years from now, the Michelson Center will soon become a hub of scientific breakthroughs in health and related fields.

Many Michelson Grantees take a similar interdisciplinary approach in their research toward development of a single-dose nonsurgical sterilant for cats and dogs. We hope to one day fund the innovative researchers at the USC Michelson Center for Convergent Bioscience with Michelson Grants.

New Advisors on Board for MPG

Two new leading experts, Dr. Josep Rutllant and Dr. Joanne Zahorsky-Reeves, have been appointed to the Michelson Prize & Grants Scientific Advisory Board.

Josep Rutllant, DVM, PhD is a professor of anatomy and embryology in the College of Veterinary Medicine at Western University of Health Sciences. Dr. Rutllant has many years of experience in general areas of sperm cell biology and function, including isolation of spermatogonial stem cells and Sertoli cells from dogs, and patterns of MHC protein expression during porcine spermatogenesis.

Joanne Zahorsky-Reeves, DVM, PhD is the Regulatory Affairs Program Administrator in the Division of Laboratory Animal Medicine at University of California, Los Angeles, also serving as a board certified laboratory animal veterinarian. Dr. Zahorsky-Reeves completed her PhD in comparative and experimental medicine and focused her postdoctoral research on xenotransplantation genetics.

Our Board advisors provide invaluable insight, individually by applying their specific areas of expertise when reviewing letters of intent and grant proposals, and collectively by fostering exciting ideas on how to bring the MPG program closer to the goal of a single-dose nonsurgical sterilant.

We welcome Dr. Rutllant and Dr. Zahorsky-Reeves in joining us to solve this global challenge!

To read more about our Scientific Advisory Board members, please visit the Board Bios page.

Three New Grantees Announced

We are pleased to announce that the Michelson Prize & Grants in Reproductive Biology has three new projects that are recently underway!

Dr. George Bentley, an Associate Professor of Integrative Biology at the University of California, Berkeley, has been awarded a two-year grant totaling $249,999 for his project titled, “Over-Expression of the Novel RFamide Gonadotropin-Inhibitory Hormone: Proof of Concept Study in Rats.”

Dr. Jonathan LaMarre, a Professor in the Department of Biomedical Sciences at the University of Guelph, will receive a two-year grant totaling $260,310 for his study titled, “Targeting piRNA/Endo-siRNA Pathways for the Control of Companion Animal Fertility.”

Finally, Dr. David Putnam, an Associate Professor in the Department of Biomedical Engineering at Cornell University, has been awarded a two-year grant totaling $352,365 for his proposal titled, “Self-boosting pathogen-like particle multi-antigen vaccine for female immunosterilization.”

We very are excited about the promise that these new projects hold for taking us closer to our goal of developing a single-dose, nonsurgical sterilant for cats and dogs. For more information about these and other current Michelson grantees, visit our Current Grantee Profiles and Research Findings pages.

Dr. Gary Michelson, the founder and sole funder of the Found Animals Foundation, has devoted up to $50 million in international grant funding through the Michelson Prize & Grants program. Since awarding our first grant in 2009, we have committed over $12 million to approved projects in nonsurgical sterilization research. We are looking forward to receiving more innovative proposals during our upcoming grant cycles in 2014!