The search goes on for a single-dose non-surgical way to sterilize dogs & cats

From ANIMAL PEOPLE, April 2010:

 

DALLAS–More than 50 contenders for the
$25 million Michelson Prize for the invention of
a successful non-surgical method of sterilizing
dogs and cats registered for an intensive
briefing about how to win the money at the April
8-10, 2010 Alliance for Contra-ception of Dogs &
Cats conference in Dallas.
The first step, for most, will be
winning some of the $50 million research and
development funding offered by Found Animals
Foundation founder Gary K. Michelson, M.D., to
help the contenders approach the jackpot.
To do that, the contenders must present
ideas that clear rigorous screening for
feasibility, practicality, and safety by the
Found Animals Foundation scientific advisors.
As holder of more than 900 patents issued
or pending worldwide for medical instruments,
procedures, and other medical devices, mostly
used to treat back pain, Michelson has a clear
idea what he wants to see: a single-dose
treatment that will quickly, inexpensively
sterilize dogs and cats for life, and can win
regulatory approval for widespread use.


If the money was equally distributed
among the applicants, Found Animals Foundation
executive director Aimee Gilbreath told ANIMAL
PEOPLE, it would soon be gone, not necessarily
with anything to show for it. Millions of
dollars have already been invested during the
past 50-plus years to develop animal
contraceptives, but no product has come close to
meeting the Michelson criteria, simple as they
are.
The Michelson Prize may go to the
inventors of an immunocontraceptive, a
chemosterilant, or some other method as yet
unknown, but it is not likely to go to anyone
soon, cautions Gilbreath.
“To our knowledge, there isn’t any
product at nearly a stage of development that is
worth getting excited about,” Gilbreath said.
“Our presentations will focus on work in the
research pipeline and discussion of what has been
tried in the past, why it hasn’t worked, and
promising new avenues for exploration.”

Why not pet food?

Animal advocates may be disappointed that
the Michelson Prize criteria do not include the
further stipulation that the winning method be
potentially accessable for unsupervised use by
individual rescuers. For more than 30 years dog
and cat rescuers have yearned for a product that
could live up to the promises that accompanied
the introductions of several different “birth
control pet foods” between 1963 and 1978.
At that time there was still relatively
little concern about the longterm effects of
birth control drugs on human health, almost no
consideration of the use of pharmaceuticals as
biological weapons, and was not yet any
regulatory attention to the effects of drug
residues in in the environment.
The “birth control pet foods” included
progestin-based hormonal contraceptives.
Repeated dosing was required, and sustained use
led often to pyometra. Two products from this
generation of animal contraceptives are still
available–Ovaban, for dogs, and Feral-Stat,
for cats. But neither is actually a sterilant.
The “birth control pet food” introduced with the
greatest fanfare, Mibolerone, was a progestin
product closely related to the post-coital human
contraceptive RU-486. It had the same issues as
the rest, however, and the active ingredient
was banned in the U.S. as an abortificant from
1988 to 2000.
“I’m not sure that we’ll ever get to
something that could be distributed by lay
people, but I bet we could get to something that
a vet tech can do–perhaps under indirect
veterinary supervision,” Gilbreath told ANIMAL
PEOPLE. “Our goal is for it to be at least as
easy as vaccinations are now,” Gilbreath added,
anticipating that the Michelson Prize will
probably be won by an injectible product.
Procter & Gamble toxicologist Mark
Lafranconi, manager of the $300 million P&G
program to develop alternatives to animal
testing, surveyed the P&G regulatory experts on
behalf of ANIMAL PEOPLE as to whether a “birth
control pet food” could gain regulatory approval
today, even if it worked perfectly in laboratory
settings.
“I have polled across our organization
and the unanimous conclusion is this type of
initiative would never receive approval,”
Lafranconi reported, “no matter what the
jurisdiction, for the reasons you have already
identified. Inability to control access and
exposure is the major limiting factor.”
Agreed Linda Rhodes, vice president for
clinical development at AlcheraBio LLC, of
Metuchen, New Jersey, a division of Argenta
Inc., “I would say that there is no chance that
the government will approve a substance to be
given to feral animals using a bait, flavored
substance or food, by lay people, given what we
know about the science today. In order to not
impact people, especially children, or other
wildlife, such a substance would have to be
completely species-specific. For example, a
drug that could only be effective in cats and no
other birds or mammals. Given today’s science,
there is no drug or substance that I can think of
that has that level of species specificity.”
The oral rabies vaccine Raboral has been
used successfully since 1969 in foxes, raccoons,
and coyotes, but only in pellets that can only
be dissolved by the stomach enzymes of the
specific target species.
“Oral rabies vaccine scattered as bait
for raccoons, fox, and other wildlife, has
been successful,” Rhodes acknowledged, “but
only because it is administered as part of
government programs, and because human or
multi-species ingestion has only beneficial
results, i.e. vaccination against rabies.”
Rhodes was previously director of
clinical development projects for production
animals at Merial Ltd., the maker of Raboral.
She now chairs the Alliance for Contraception in
Dogs & Cats board of directors.
Whether a new “birth control pet food”
could be marketed today “really will depend on
the country,” said Humane Society of the U.S.
chief of staff Andrew Rowan, an ACC&D board
member who has professionally followed
developments in toxicology and birth control for
more than 30 years.
“You can buy all sorts of medications
over the counter in many developing countries
without much in the way of regulatory oversight,”
Rowan pointed out, “so if one could develop a
chemosterilant that was not too toxic, it could
find its way to the market in some countries for
use by the general public. In the U.S.,”
Rowan suggested, “it would depend how it was
classified. If it was viewed as an animal
health product, then the veterinary profession
would be loath to cede control over
distribution. If it was classed as a pesticide,
the situation would be different. You can look
at Ovocontrol as an example. It is available in
the U.S. for use by non-medical people because it
is classed as a pesticide. Of course,
something targeted rather narrowly at bird
reproduction is likely to be treated rather
differently from a chemical that interferes with
mammalian reproduction.”
Offered David M. Petrick, who is both a
veterinarian and a lawyer, and heads Delta
Consortium Regulatory Consulting Inc. in
Princeton, New Jersey, “If the issue is whether
a product will be offered for sale
over-the-counter, at which point all
professional judgment is lost, I don’t think so,
but it will certainly depend very specifically on
the product itself, how it is administered, the
margin of safety, and safety to the
environment. But even if the product is a
prescription veterinary drug, the regulations
state they can only be used ‘by or on the order
of a licensed veterinarian.’ In this case, ‘on
the order’ could certainly mean a group of
volunteers designated and trained by a
veterinarian, who would be supplying the product
and who would be responsible in the Food & Drug
Administration’s eyes. Likewise, if the
Environmental Protection Agency were involved,
EPA may require a certified pesticide applicator
to use the material, in which case it would not
be a vet, but a licensed pesticide professional.”
Petrick previously worked in regulatory
affairs and product development for both American
Cyanamid and Schering-Plough Animal Health. He
is also vice president of regulatory affairs for
Velcera Pharmaceuticals.
USDA Animal & Plant Health Inspection
Service regulatory specialist John Eisemann,
identified by Janet Raloff of Science News as
“the go-to guy for identifying what permissions,
waivers or requests are required before wildlife
managers can apply poisons or anti-fertility
drugs,” told the spring 2010 national meeting
of the American Chemical Society about “legal
tactics by which wildlife officials can thwart
invasive vertebrate species with off-the-shelf
chemicals,” Raloff wrote in the March 22, 2010
edition of Science News.
“He noted, for instance,” Raloff
continued, “how scientists have used a
contraceptive vaccine,” called Gonacon,
“designed to control white-tail deer populations,
on rodents. It offered a nonlethal approach to
reining in a population explosion of non-native
fox squirrels on a University of California
campus. In another instance,” Raloff said,
“wildlife managers employed a cholesterol
inhibiting drug to reduce sex hormone levels–and
the urge to reproduce–among monk parakeets.”
So some openings may remain for
introducing a “birth control pet food,” if such
a product is developed, even if it does not meet
the Michelson criteria.

SenesTech

Despite expert skepticism, a June 2008
report by Arizona Biosciences News rekindled hope
that a “birth control pet food” might be just
around the corner.
The report focused on the work of a
company called SenesTech to develop a rodent
birth control product called ContraPest.
“Until recently,” said Arizona
Biosciences News, “the active ingredient in
ContraPest was known in the scientific community
mainly as a menace. The industrial chemical
4-vinylcyclohexene diepoxide, or VCD, is widely
used in manufacturing products such as tires,
polyesters, and epoxy resins. Women working in
industrial settings who have received high-dosage
exposure to VCD have suffered serious
reproductive damage.”
Partnering with the Australian
government’s Invasive Animals Cooperative
Research Centre, SenesTech has tested VCD as a
possible way to sterilize rats and wallabies.
SenesTech has also experimented with a VCD
product for dogs called ChemSpay.
Concluded Arizona Biosciences News, “One
of SenesTech’s first tests of ChemSpay occurred
on the Navajo Nation.” SenesTech founder Loretta
Mayer’s team “treated 170 dogs with VCD; all
are sterile, and none have died. With funding
support from the U.S. Humane Society, SenesTech
is continuing research toward a single-injection
treatment that veterinarians and public-health
officials could use to control overpopulation of
both domesticated and feral dogs and cats.”
Rowan was unable to identify any
involvement by the Humane Society of the U.S.,
but HSUS is a major funder of the Alliance for
Contraception in Cats & Dogs, and ACC&D did fund
one early study of ChemSpay.
Explained ACC&D president Joyce Briggs,
“ChemSpay, initially developed to model human
menopause in mice, was a novel approach to
non-surgical sterilization which piqued our
interest early on. ACC&D funded a small study in
2006 to evaluate whether the ChemSpay approach
may be effective in dogs. That study was not
able to demonstrate effectiveness. SenesTech’s
subsequent work has focused on mice and rats,
though representatives of the company have said
that they plan to return to work on formulations
for cats and dogs in the future. ACC&D recognizes
that this approach is in very early stages in
terms of applications in cats and dogs. We have
asked SenesTech to keep us apprised of progress ,
and will share any relevant, non-proprietary
information that becomes available.”
SenesTech did not respond to repeated
inquiries from ANIMAL PEOPLE in 2009 and early
2010. According to the SenesTech web site,
“Consumption of ContraPest will cause female rat
sterility within one month of ingestion.
ContraPest is being formulated in a rat
attractant specific bait minimizing consumption
by non-target species. Our product is
environmentally neutral. It is rapidly
inactivated in dosed rats and the excreted
metabolite is inactive. ContraPest will not
bioaccumulate nor enter the food chain.
Therefore predators of the rats will not be
accidentally dosed. The rats who consume the
ContraPest bait have no physiologic changes other
than elimination of all eggs in the ovary,
resulting in permanent sterility. It is expected
to be marketed within two years to the 13
Southeast Asian countries that are responsible
for the vast majority of world rice production.”
Confirmed Australian Commonwealth
Scientific and Industrial Research Organisation
vertebrate pest stream leader Lyn Hinds, “I have
been undertaking trials on this chemical product
here in Australia and in Indonesia. However,”
she said, “due to the commercial-in-confidence
nature of the research, no specific publications
or details of the results are available at this
stage.”
VCD studies
But scientific journals have reported
about the contraceptive effects of VCD.
Headlined Toxicology and Applied
Pharmacology in August 1999, “A Single Dose of
the Ovotoxicant 4-Vinylcyclohexene Diepoxide Is
Protective in Rat Primary Ovarian Follicles.”
Though longterm exposure to VCD can produce
sterility, the five co-authors concluded that
“These data provide evidence for a ‘protective’
response against the normal rate of atresia in
primary ovarian follicles following exposure.”
Since the Michelson Prize requires that
the winning substance be effective after a single
dose, this finding would appear to exclude
ChemSpay.
Summarized a 2001 report in Biology of
Reproduction, “Following 30 days of daily
dosing, the majority of small preantral
follicles in immature as well as in adult rats
are destroyed. Previous studies have shown that
15 daily doses of VCD (80 mg/kg, i.p.) destroy
about 50% of oocytes contained in small preantral
ovarian follicles in rats.”
In other words, a VCD product might have
to be administered every day for two weeks to a
month to be effective.

VCD is carcinogen

VCD can have other effects. The
International Agency for Research on Cancer found
in 1994 that “Skin application of VCD produced
benign and malignant skin tumours in all studies
in mice and in a study in rats. In one study in
mice, it also increased incidences of ovarian
and lung tumours in females.”
National Institute of Environmental
Health Sciences researcher James Huff confirmed
in Toxicological Sciences in 2001 that VCD
“induced both squamous cell and basal cell
neoplasms of the skin” of most male and female
rats and mice. “Both benign and malignant tumors
of the ovaries were caused by dermal exposure in
female mice,” Huff added, also noting a
possible association of VCD exposure with lung
cancer in mice.
The production of squamous cell tumors is
of particular concern in considering VCD
applications for use in dogs and cats. Explains
University of Illinois veterinarian Sandra Manfra
Marretta in Recognition and Treatment of Oral
Tumors, “Squamous cell carcinoma is the most
common oral tumor in the cat and is the second
most common oral tumor in the dogŠThe prognosis
in dogs with oral squamous cell carcinomas if
therapy is timely and correct is fair with
approximately 50% of treated dogs living one
year. The prognosis in cats with oral squamous
cell carcinoma is very poor because of the rapid
growth of this tumor in cats.”
Pharmaceutical developers often thread
their way through a maze of potential obstacles
to perfecting and marketing new products,
including the possibility that an ingredient may
cause cancer at particular dose levels. Thus the
published studies indicate not impossibility so
much as the potential degree of difficulty
involved in perfecting ChemSpay and winning
regulatory approval for it.

600 Million

But almost a year and a half after the
Arizona Biosciences News appeared, ANIMAL PEOPLE
heard from five different animal advocacy donors
and fundraisers, just a few weeks apart, that
ChemSpay or an unnamed similar product will, as
one put it, “Change the world!” One of them
specifically cited SenesTech as the developer.
Four of the five, including the one who
mentioned SenesTech, turned out to have
associations with a new nonprofit organization
called 600 Million Stray Dogs Need You, headed by
Alex Pacheco, who cofounded PETA in 1981 and in
1998, after leaving PETA, briefly headed the
New England Anti-Vivisection Society.
Wrote Pacheco in a December 13, 2009 web
posting, “We are talking with scientists about
teaming up to develop animal birth control
pellets that will allow us to end a vast amount
of suffering around the world. It’s a long,
expensive and complex process that involves
everything from getting FDA and EPA approval to
negotiating with the governments of impoverished
nations, where we plan to distribute the birth
control pellets for free.”
The 600 Million rhetoric escalated in
connection with a February 28, 2010 dinner
hosted by Animal Rescue Resource Found-ation
cofounders Craig and Pam Neilson, of Vista,
California, to promote investment in developing
a “Super Birth Control Pill for Dogs.” The
Animal Rescue Resource Foundation, formerly
called the Give Some Life Foundation, has funded
surgical sterilization of more than 10,000 dogs
in northern Mexico during the past seven years.
Elaborated a 600 Million appeal mailing,
sent in mid-March, “We are in the process of
developing specialized, long-term ‘super’ birth
control pills (in the form of food pellets) for
dogs… formulas that will provide years of
contraception, from just one doseŠIt must be a
pill. Injections will not solve the problem
because they are too difficult to administer to
millions of dogs running loose. Pills on the
other hand can easily be mixed with food. We are
in the process of hiring scientists to fast-track
this. We are building a network to enable
distribution of the pill in more than 60
countries.”
Asked for specifics, Pacheco told ANIMAL
PEOPLE only, “I have access to data and
documents which you do not.” Pacheco said he was
“preparing a list of additional documents and
statements for publication,” and would “release
the documents when they are ready to be
released,” but the only new item he released in
the next three weeks was a letter similar to his
own appeals, signed by Jeff Young, DVM, of
Planned Pethood Plus in Denver, who also cited
no specifics about the birth control product.
Noted ACC&D director of outreach Karen
Green, “Alex has not publicly named the
technology he’s referring to or the partner he’s
working with. SenesTech would make some sense,
since that technology most closely matches Alex’s
claims about a permanent sterilant delivered
orally. However, the SenesTech approach is
still in very early stage research in terms of
proving efficacy and safety in dogs and cats,
and beyond that stage, there are years of
hurdles to getting regulatory approval. While we
would love to see something available that
matches Alex’s description, I’m afraid
we–including our network of directors,
scientific advisors, and colleagues in the
field–have seen no evidence that such technology
is anywhere near.”
Added Green and Briggs in a written
statement, “We are pleased to see other
organizations working on new ways of controlling
pet populations. We hope that 600 Million Stray
Dogs Need You will help raise awareness about the
need for new ways to control reproduction in
animals.
“Until the recent announcement about the
near-ready ‘super birth control pill,'” the
statement said, “the stated goal of 600 Million
Stray Dogs Need You was to create a birth control
pill for animals–focusing on dogs–which
provides contraception for at least six months
and can be mixed into food for easy delivery.
ACC&D has long believed that cat and dog
contraceptives must be long-lasting–a minimum of
three years, but ideally permanent–in order to
have significant impact. Particularly for the
stray and free-roaming dogs in developing
countries, a product requiring semi-annual
treatment is impractical. While we do believe
there may be niche use for a product lasting six
months, we believe such a product is unlikely to
be effective for large-scale population control.”
ANIMAL PEOPLE president Kim Barltett
disagrees. “Since true street dogs– not
‘community dogs’– in the developing world have
an average lifespan of around three years, with
possibly five breeding cycles for each female who
survives that long, an oral birth control
formula lasting six months would have the
potential to cut breeding by about 20%. This
would be a huge reduction in the birth rate by
itself, and if the product were effectively
administered twice a year to all the female dogs
in an area, the birth rate in the treatment area
would plummet. There are a lot of variables and
plenty of opportunities for improper dosing, but
I disagree with the conclusions of ACC&D that a
contraceptive lasting only six months would have
an insignificant impact on a street dog
population.”

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