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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