44 Saber Tails Summer 2019
Petit Basset Griffon Vendéen Club of America
Dr. Komáromy recommends testing
all offspring of
‘clear by parentage’ parents.
The crisis has lessened but it is not over. Of the 509 PB-
GVs in North America who have been tested so far (as of
February 2019), 205 are carriers of the POAG mutation.
Responsible PBGV breeders have had their breeding
stock tested. They are aware of the need to breed carriers
to clear in order to avoid producing affected offspring,
and the need to test the litter. However, as Dr. Komáro-
my noted, mistakes are inevitable and not all breeders are
responsible. Thus, it is likely that affected PBGVs will be
born in the future.
In particular, Dr. Komáromy spoke about the designa-
tion ‘clear by parentage’. If a sire and dam have both
been DNA tested and are designated as ‘clear’, then their
offspring can be designated as ‘clear by parentage’ and do
not have to be tested. The Orthopedic Foundation for
Animals (OFA) will only clear by parentage for one gen-
eration. Offspring of a second generation (sire and dam
are both clear by parentage) must be tested. The PBGV-
CA policy is less stringent and will allow the offspring of
‘clear by parentage’ parents to also be designated as ‘clear
by parentage’. Dr. Komáromy recommends following
the OFA guideline and testing all offspring of ‘clear by
parentage’ parents since the world is not perfect and mis-
takes can happen on the part of the breeder or the testing
lab. The expense of testing every other generation must
be weighed against the emotional and financial costs of
producing a litter with affected puppies.
Beagles are leading the way. The most exciting news
in Dr. Komáromy’s seminar centered on his laboratory’s
progress in developing a gene therapy for POAG. Dr.
Komáromy maintains a research colony of Beagles that
develop POAG due to a mutation in the ADAMTS10
gene (a relative of the ADAMTS17 gene that leads to
POAG in PBGVs). He has cloned the normal (function-
al) version of the ADAMTS10 gene into a commonly
used gene therapy vector, called adeno-associated virus.
In Dr. Komáromy’s trial, six pre-symptomatic Beagles re-
ceived intraocular injections of the therapeutic virus in
one eye each. Their other eyes served as untreated con-
trols. The results so far have been very promising. In 4
of the 6 dogs, intraocular pressure in the treated eyes
remained low while pressure in the untreated eyes started
to rise. Two dogs showed no effect of the therapeutic
virus, which may be due to the low dose that was given.
Dr. Komáromy thinks that a slightly higher dose of virus
might be necessary to get 100% effectiveness. Fortunate-
ly, the only adverse effects have been slight inflammation
in the treated eyes.
PBGVs could take the lead. Will this promising gene
therapy for POAG be tested in PBGVs? Is it safe? When
can it begin? These are all questions that Dr. Komáromy
fielded after his seminar. He said that the first step is to
adapt the virus for PBGVs so that it expresses the AD-
AMTS17 gene that is defective in PBGVs, rather than
the ADAMTS10 gene that was used in Beagles. This
step should be straightforward. Then the virus should be
tested in one or two pre- or early-symptomatic PBGVs.
Dr. Komáromy estimates that this could happen within
the year. Dogs would need to undergo detailed eye ex-
ams before and after the viral treatment. If there were
no or minimal adverse effects, then treatment could be
extended to other affected PBGVs.
We discussed the possibility of Dr. Komáromy obtaining
federal or foundation funding to cover the expenses of an
experimental gene therapy trial in PBGVs. The chances
of funding a PBGV trial seem slim given that there are
so few affected dogs. However, the chances go up when
we take into account that the same gene therapy could
be useful for the many breeds that are susceptible to pri-
mary lens luxation due to ADAMTS17 mutation. Thus,
successful gene therapy of POAG in PBGVs could be the
first step towards widespread gene therapy of primary
lens luxation. PBGVs could take the lead in develop-
ment of a treatment for a more prevalent eye disease.
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