Dr. Michael Tranfaglia serves as Medical Director and Chief Scientific Officer of FRAXA, a nonprofit organization based in Newburyport, Massachusetts, which is committed to finding a cure for fragile X syndrome. Dr. Tranfaglia is responsible for coordinating the FRAXA foundation’s research strategy and works with university and industry scientists to develop new therapeutic agents for Fragile X, autism, and related developmental disorders. He graduated from Harvard University with a BS in Biology and studied medicine at the University of North Carolina at Chapel Hill. After obtaining his MD from UNC, he stayed on for Psychiatry residency training, and then entered private practice in 1991. Dr. Tranfaglia was a psychiatrist by training and had specialized in the treatment of Anxiety Disorders prior to his son’s Fragile X diagnosis in 1992 prior to founding FRAXA with his wife in 1994. CEO of Global Genes, Nicole Boice, will be presenting an award honoring Dr. Tranfaglia at the 5th Annual Global Health Repurposing Awards (GHRA) which celebrate the power of re-purposing via using existing drugs, devices and nutraceuticals to create new treatments for unmet medical needs.

Dr. Michael Tranfaglia was kind enough to talk with us and explain what drives him and how he became so involved in fragile X syndrome research.

“Our son Andy is 28-years-old, and was born in 1989 with fragile X syndrome. He had some developmental delay that was not really associated with any kind of major illness, and I think this is probably the big difference between fragile X and a lot of other disease. Fragile X is kind of unique among other genetic diseases as in it’s a gene that’s affected  and is really mostly involved in synaptic plasticity and development of the central nervous system. So, these kids are healthy—you don’t really think of children with a genetic disease being perfectly healthy just having some mental problems. With fragile X these kids don’t have any medical problems persay other than a seizure disorder—which once again is part of the brain development issues.

The typical diagnosis happens around age three for anyone who doesn’t have an obvious family history. Now since it’s a X-linked disorder it not only runs in families, it runs very strongly in families. It’s not unusual to have multiple kids in the same family who are affected. Sometimes diagnosis happens prenatally because of other affected siblings within the same family.

Our daughter Laura was diagnosed with Fragile X as an infant. She was only a year old when her brother was diagnosed so the first thing we did was have her tested. If you look at the numbers, and age of diagnosis for all kids of Fragile X it’s actually artificially skewed a bit lower for people who have affected siblings. Because typically as soon as one child is diagnosed, then everyone else gets tested and that includes cousins and other branches of the family.

When our son got diagnosed, we had no known family history of Fragile X—and that’s actually about sixty percent of the new cases of Fragile X. There must be a history but no one has been diagnosed.

The first thing we did when Andy was diagnosed was scour our family history. That’s not totally uncommon, but I supposed the more common presentation is that a child gets diagnosed with Fragile X and then when they start looking around in the family tree they start realizing that Uncle so-and-so has always been mentally disabled. And that must be why.

Every once in a while the families be tested and get diagnosed.

It’s a little tricky. We’ve gone through a phase where Fragile X has been diagnosed much more commonly and we even made it to the phase where the awareness for Fragile X outstripped the occurrence of Fragile X. So a lot of people got to thinking it’s a little over-hyped. And there’s been a little bit of concern about the numbers. The official statistics were that about 1 in 2000 people have fragile X syndrome. Then they started saying it’s tremendously undiagnosed and started doing studies in an number of different ways to find the real statistics and began developing new numbers.

We’re just not coming up with that many people with fragile X.

Bigger studies and more rigorous methodology—but mostly we’ve settled on a basic estimate 1 in 3,000-4,000 people all around the world having the full mutation of the fragile X gene.

There are certain local populations that are more heavily affected because they have more founder effects. For example, there’s a little town in Venezula where every body is related to everybody else. It’s a little jungle and they’ve got a phenomenally high incidence of fragile X. But there’s always going to be place like that in the world.

Generally speaking it’s present in all racial and ethnic groups that have been studied.

Kids, especially boys, who have any kind of displayed developmental delay can be tested for fragile X. It’s a very accurate DNA test that detects this trinucliatide repeat. 

When it was first discovered, the big news about Fragile X was that an odd new mutation had been uncovered and it was the trinucliatide expansion itself that was the big news and not really the disorder. It turns out that it is the same kind of mutation that causes Huntington’s disease and Friedreich’s Ataxia and a number of other conditions. So this is actually an important new mechanism to understand. In the case of fragile X  it really all boils down to not producing the protein. So every gene is important because it produces a protein. And in the case of Fragile X it’s a bunch of different isophorms. People who have fragile X don’t produce this protein.

Now females.

Our daughter is perfectly within the normal range in every way. That’s not to say that’ she’s totally unaffected. We don’t really know what she would be like without the mutation. Our daughter is twenty-five, just got married, graduated from college, didn’t really have any problems. Maybe she would have done better if she didn’t have fragile x—but we don’t really know. You would never think that she had a condition. The only thing that it affects for her now is that she’s in her childbearing years.

The way we think of fragile X now, it’s basically just autism. Most people don’t really know what autism is like if they haven’t interacted with it directly anyways. People with Fragile X would just strike you as being autistic. They have consistent intellectual impairment. Some people have high-functioning Autism, but that doesn’t happen in fragile X. In fragile X, they have a below average IQ and generally test far below average. That turns out to be true with most autism cases as well. Most people with autism have pretty significant intellectual impairments. It’s just that there’s much more of a range in people with idiopathic autism (or undiagnosed causes of autism.)

It tends to be global delay in developmental milestones. Typically when kids are toddlers, the pediatricians are always looking at their developmental milestones—when do they sit up? When do they crawl? When do they walk? When do they talk? Are they toilet trained? That kind of stuff. Kids with Fragile X tend to first show problems with delays in those basic milestones which range from  motor milestones to cognitive milestones—all seem to be delayed. As with everything, there are outliers are some kids that walk and talk at a normal age and still have fragile X. Generally speaking what happens, being a disorder of development, they get further and further behind as they get older. Meaning that children with Fragile X tend to be born normal babies with no obvious defects who just don’t quite develop at the normal rate. And really it depends on how far behind they get and how quickly they get behind that allows suspicion for pediatricians to test for Fragile X—especially if there’s no family history.

Generally speaking, in the US, pediatricians are pretty aggressive in chasing down any developmental delays. That is not the case everywhere. We were just in touch with a Canadian family that is on a very long waiting list to get to see a geneticist and for their son who they believe has fragile X and is already well beyond age three. They’re waiting to get an appointment and that won’t be for another year or so. 

The awareness of fragile X now is considerably greater than it was.”

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