 More
than 40 years after Dr. Jérôme Lejeune discovered that people with
Down syndrome have an extra chromosome in their cells, the basic
mechanisms behind the intellectual and neurological disabilities
associated with this genetic disorder remain unknown. As a neuroscientist,
trained physician, and the parent of a six-and-a-half-year-old
girl with Down syndrome (Tyche), I have spent the last five and
a half years of my career searching for a potential drug therapy
for this genetic disorder. During these years, I have had many
positive professional experiences, such as being the recipient
of the NDSS Science Scholar Award, being the only person awarded
with a major grant from the NIH to study exclusively potential
pharmacotherapies for Down syndrome, and serving as a co-organizer
of the last International Chromosome 21 Meeting. Of course, during
this time, I also have had my fair share of frustration. Frustration
not only with the normally slow pace of scientific progress,
but also with the amazingly low amount of research support for
this field.
About
two months ago, under the sponsorship of the MHDSA, I presented
a seminar at the Eleanor Roosevelt Institute entitled: "In
Search of a Pharmacotherapy for Down Syndrome." The goals of
that talk were to share with other parents some of the recent research
findings from my laboratory, as well as to review some of the current
ideas on the nature of Down syndrome. I also took the opportunity
to voice my opinions on the origins of the disproportionally poor
funding for Down syndrome research compared to other disorders that
lead to intellectual disabilities. Therefore, I was pleasantly surprised
to see that one of the consequences of that seminar was to fire
up the interest of many of the parents not only for Down syndrome
research but also for the issue of funding for Down syndrome
research. At
the request of friends at the MHDSA, I will write about what was
said in that seminar.
My
view of the impact of trisomy 21 on people's cognitive abilities
is essentially the same as voiced by the late Dr. Lejeune in his
1990 article ("Pathogenesis of Mental Deficiency in Trisomy
21") in the American Journal of Medical Genetics:
"[Down
syndrome] is an implacable disorder depriving the children of the
most precious quality afforded by our genetic patrimony, the full
power of rational thinking."
The driving force for my work, and the philosophy of my laboratory,
is the idea that the intellectual disabilities associated with Down
syndrome may be at least partially reversible. We hypothesize that,
akin to what happens in many psychiatric and neurological diseases,
a significant component of the intellectual disabilities associated
with Down syndrome is the result of a dysfunction in the ability
of neuronal cells to communicate to each other. (Note that, as a
parent, I am much less offended by the word disease than
by expressions such as birth defect and chromosomal aberration,
which are still very popular in many modern books of medical genetics.)
That is why a large part of our current work focuses on looking
for differences in the way brain cells from mouse models of Down
syndrome communicate to each other as compared to cells from typical
mice.
From
these studies, as well as neurological studies involving persons
with Down syndrome that have been carried out in my laboratory
and by others, a somewhat fuzzy but promising picture is emerging.
We hope to have enough data in the near future to start building
a rational basis to test potential drug therapies for Down syndrome.
As it has been the case for many modern therapies, any potential
treatment probably will be tested first in animal models and
then in persons with Down syndrome. Such development can potentially
lead to a significant leap in the quality of life of individuals
with Down syndrome. Of course, because of the very nature of
the scientific work, there is no guarantee that any of this will
ever work. What is absolutely certain, though, is that it never
will if we do not keep trying!
Now,
back to the issue of funding for Down syndrome research . . . Why
is it that autism, fragile X syndrome, or even Rett syndrome (which
affects less than one in 10,000 people worldwide) get so much more
research support, from both private and federal sources, than Down
syndrome? I think that at least part of the blame lies in the prevailing
culture of the parent community. For example, even the apparently
straightforward idea of comparing the intellectual disabilities
associated with Down syndrome to a psychiatric or neurological disease
may seem odd to many parents. After all, one of the greatest achievements
of parents who raised children with Down syndrome in the 1970s and
80s was that through massive advocacy efforts, they were able to
increase the level of inclusion of people with Down syndrome to
unprecedented levels. In this process, much of the language originally
used by the civil rights movement of the 1960s and 70s was incorporated
to the discourse of various advocacy groups for people with both
physical and intellectual disabilities. That is why we hear many
times expressions such as "segregated or integrated schools"
and so on and so forth. Whereas there is nothing wrong about borrowing
from a successful model, it is also accurate that we cannot have
it both ways. If we accept that the intellectual disabilities, which
represent an integral part of having Down syndrome, is simply an
immutable condition or just another variation of the
typical human experience, this would obviate the need for research
in this field. This would be especially true for research like the
one that is carried out in my lab, where we have made it our primary
goal to search for a drug therapy for Down syndrome.
At
the present time, a much more productive attitude would be for
all of us to confront the intellectual disabilities of our children
as an undesirable result of brain dysfunction and to support
state-of-the-art research designed to understand the basis of
this dysfunction and potential ways of significantly alleviating
it. As the popular saying goes: "accepting that you have
a problem is the first step to recovery." Please note that
I am not proposing that we lower our guard in terms of advocacy
efforts, because such efforts are still very much needed. Neither
am I saying that we should not be embracing and loving our children
and striving to help them achieve their full potential with
existing resources. But I think it would be very presumptuous
of us parents of children with Down syndrome to assume that
somehow we are better parents than other parents of children
with disability. While keeping the advocacy pressure up, parents
of children with autism in Canada put together an incredibly
successful organization with the bold name "Cure Autism
Now."
Also highly successful in raising research funds is the fragile
X organization called FRAXA, which also is raising money for research
on potential drug therapies to improve the cognitive abilities
of individuals with this genetic condition. Spurred by the efforts
of such parent groups, nowadays some of the most influential neuroscientists
in the country, including Nobel laureates, are doing research
in the fields of autism and fragile X. Given the lack of available
funding, the popularity of Down syndrome research among such scientists
is unfortunately much lower.
Historically,
whenever firm scientific knowledge is lacking in any given area,
mythology, "educated guesses", and plain old opportunism
tends to fill in the vacuum. That is how, by preying on the hopes
of many parents, a plethora of so-called alternative therapies have
been developed. These include various incarnations of nutritional
supplements, chemical agents not typically meant for human use like
DMSO, ineffective and unpredictable medicines like piracetam, and
bizarre and potentially dangerous things like sicca cell therapy.
During
a recent conversation on alternative therapies, a friend shared
a piece of family history that I thought was quite pertinent to
the issue of Down syndrome today. My friend's mother, a registered
nurse, struggled with the attention deficit hyperactivity disorder
that affected her son as a child growing in the mid 1970s. After
exhausting all the psychotherapic options available, she was desperate
enough to try a few of the many diets then available that claimed
to "cure" ADHD. Of course, none of these worked either.
That was when a new pediatrician suggested that she try the then
new medication called Ritalin. After only a few days, the
behavior of her son improved dramatically. Today, from a troubled
child and a potential sub-employed dropout he is a responsible married
man with a great job in the computer industry. The main two lessons
we can all learn from this story are: 1) diets and portions may
make some parents "feel good" about themselves because
they at least feel they are trying something, but, if the therapy
does not address the basic underlying problem, it will not have
a positive effect on the child; 2) a correctly prescribed drug therapy
may have positive effects even on school-age children with at least
one form of developmental disorder. Of course, one should also be
aware that, just like any other psychoactive drug, there are risks
of overprescription, abuse, and other potentially dangerous side
effects with the use of Ritalin and similar agents in the treatment
of ADHD. But at least there is a real pharmacotherapeutic option
that has proven to have positive effects on a significant number
of individuals affected by this condition. The same is not true
yet for Down syndrome.
To
finish this article, I would like to leave you with the words of
the Scottish special educator and Down syndrome researcher Dr. Jennifer
Wishart, who dared to see beyond the political correctness of the
time and said:
"It is still the case that many children with DS do not progress
beyond the capabilities of the average 6-8 year old, with a significant
number failing to achieve even that. Children with DS may be leading
healthier and happier lives and benefiting greatly from the growing
acceptance of their right to take their place in the community but
we are still failing them when it comes to identifying ways
of helping them to compensate for the very real problems they encounter
in learning basic childhood skills [bold and italics added
to the original text]."
(In
"Cognitive abilities in children with Down syndrome: developmental
instability and motivational deficits. Prog Clin Biol Res, 1995,
393:57-91")
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