A Rare Disease Patient Perspective

I would like to use this blog post to explain why the rare disease community is different, and why it deserves a different approach to the approval of treatment.

This weekend I started reading Inside the FDA: the politics behind the food we eat and the drugs we take. In one of the first chapters of the book, the authors describe criticism that the FDA received after approving SSRIs, a special class of anti-depressants. Briefly, the drugs were tested in adult patients and later prescribed en masse to adolescent patients. Many of these patients had horrible side affects, including suicidal or even homicidal episodes.

It is very scary to me that cases like that could affect the approval of the potentially life-saving drug that my son needs. Our son Reed is 4 and has Sanfilippo Syndrome, a very rare disease that is life-limiting. Patients typically live to age 15 or so. The disease is neurodegenerative – meaning that while they live, their brains and nervous system accumulate a waste product that gradually degenerates all their abilities.  It even affects their personalities. It is one of a group of genetic disorders referred to as MPS diseases.

So what makes the rare disease community different from ordinary potential drug consumers?

We are informed

Rare disease patients are informed. I hate to say it, but often we are more informed than many of the local doctors we visit on the state of science and medicine as it relates to our conditions.

Within the first week of our son’s diagnosis, we reached out to the leading experts in the world on Sanfilippo syndrome. I had detailed conversations with them. I spoke with Liz Nuefeld at UCLA. Dr. Nuefeld is the matriarch of Sanfilippo research and someone who has spent a lifetime trying to help develop treatments for children like my son. She spoke to us for an hour from her office on a Saturday. Dr. Nuefeld painted a very dire picture regarding the prognosis for our son. She was very frank, honest and caring.

Dr. John Hopwood from University of Adelaide gave me a call from his office in Australia and spoke with me in detail about what HE would do if his son was affected. He urged me to try very hard to participate in the intrathecal enzyme replacement drug trial.

I asked him very careful questions about risk versus benefit. I recall asking him “Is it risky?” His response to my question? “The risk without treatment is a 100% chance of death.”

We talked about the competitive landscape for treatments, about the use of genistein and gene therapy, etc. His viewpoint was that the first treatment which would likely help Reed is intrathecal (IT) ERT. I trust Dr. Hopwood for two reasons 1) he actually did studies which showed the effective diffusion of intrathecally administered enzyme replacement in dogs (which are similar in brain size to humans; 2) he is a man that clearly cares. Dr. Hopwood travels the world attending MPS research conferences and actually stays with families. He is connected to the community, not sitting in an office somewhere far removed from the people who are suffering. He understands our plight.

I contacted Shire (the company developing the intrathecal enzyme replacement therapy for Sanfilippo syndrome) and spoke directly with the medical director for the Sanfilippo program. He is a very kind man, who is clearly very sympathetic. I don’t envy his position – having to constantly deal with desperate parents like me. He spent over an hour with me, and has been very honest and open with me in our conversations.

I also spoke with Dr. Emil Kakkis. Dr. Kakkis has started the Every Life foundation with the goal of speeding lifesaving treatments to the clinic for children like my son. Emil has spent a lot of time with me, in person and on the phone. He understands the drug development process, because he has lived it, many times.

Is this unique? No. But try reaching out and pulling together a phone call with world leading experts on cancer, heart disease, Alzheimer’s, etc. You would not be able to do it.

We are connected

A new world in the rare disease space was opened by the advent of blogs and social media. Twenty years ago, it is likely that parents of a child with a rare disease would not have met another child with a similar rare disease, or talked with their parents. Now I can see pictures on Facebook and I can see, first hand, the trajectory that children affected with Sanfilippo and Hunter Syndrome will take without treatment. It is heartbreaking, but it is also empowering and motivating.

Perhaps more importantly, it is very hard to “control the message”. I read blogs every day and learn about the lives and progress of patients undergoing similar treatments for diseases similar to my sons. A couple of favorites of mine are Saving Case and the Purcell family’s blog. These are the blogs of families whose children have Hunter Syndrome, a disease similar to Reed’s –one for which intrathecal enzyme replacement therapy is already under a clinical trial in the United States. Their blogs, and those of others, inform the MPS community about children who are participating in Shire’s intrathecal ERT treatment in the United States for that disease.

I speak regularly with these parents and follow closely their status as they work to get admitted to trials, understand their trials and tribulations (no pun intended), and I get their perspective on risk vs. perceived benefits. These are passionate and empowered people. Their perspective has provided great insight to me.

Patients are connected in a way that has never existed previously. If they were mistreated and losing faith in the general approach I would know it– and it would, frankly, influence my decision about future choices for my son. That is amazing power in the hands of consumers.

We are empowered

I have already touched on this with my “connected” point. To emphasize it, I would like to state it in a different way. Sanfilippo Syndrome is rare. My understanding is that roughly 50 babies are born each year who will ultimately be found to have MPS IIIA (Reed’s subtype). That means Reed represents 2% of the potential consumers of any MPSIIIa treatment who were born in 2007.

It is true that Shire’s IT ERT is likely the treatment option that will be available any time soon. However, there is a rich pipeline of potential treatments.

Zacharon has partnered with Pfizer to come to market with a small molecule drug. This small molecule drug has some wonderful potential advantages. If it works, it would potentially be a systemic treatment for the disease (treating more than the brain and CNS) and would likely be a pill or a patch. The big risks with this treatment are timing and proof about whether it works.

A gene therapy trial has launched in Paris. It should begin any day. Proponents claim it will expand to many participants very quickly. The advantage and disadvantage of this approach are that gene therapy is at least semi-permanent. It works by helping the body actually produce the missing enzyme. The risks here are unknown and potentially catastrophic.

Give me the choice between an effective treatment for my son, and something as radical as this, and I choose treatment any day. But will I have that choice?

At some point, new options will be available. We, as parents and consumers, are very well-informed, and have carefully weighed the risks as best we can. If we choose one treatment or another, it is because I have carefully weighed the perceived risks and understand my options.

We represent a great unmet need

Parents are desperate. In the absence of other options, almost any of us would choose desperate measures. Many parents of Sanfilippo kids gave their kids stem cell transplants. Stem cell transplants are extremely risky (20-30% mortality) and, in hindsight, don’t work.   These parents took the only shot available–TO USE AN APPROVED TREATMENT, HOWEVER DANGEROUS.   Sadly, for the ones who did, it doesn’t seem to work. I don’t fault them for trying, and would likely do the same thing in their shoes. Faced with the tough choices that they faced at the time, they took their only shot. What we need are better choices.

Simply holding back on allowing better treatments does not prevent people from taking risks. It forces people into a corner where they must take undesirable risks.

Without help, children will die. We were all reminded of this stark reality by hearing about the death of Rachel last week – a 9 year old girl with Sanfilippo syndrome. This awful fact only heightens my sense of urgency to act on the behalf of Reed and children like him. These kids deserve better treatment options. The science exists — John Hopwood effectively treated dogs with the disease using intrathecal ERT in 2007. Now, five years later, we still can’t try this option in humans here in the United States.

Our children don’t have time to wait. Every day that goes by, we are one day closer to losing our child. For parents, it feels like the weight of the world is on our shoulders.


People with diseases like Sanfilippo syndrome deserve the opportunity to be given treatment. THIS patient community and THIS disease DO NOT correlate well to issues like depression. We are a small tightly knit community, and we know and understand the options. We understand the risks. We choose to take risks because the risk of death is 100% if we do nothing. We are smart, sophisticated and empowered.  We deserve the opportunity to choose the best options for our children.

We have desperate consumers and willing providers. So what is the problem? I will tell you that this is a very, very difficult question to get answered. One thing I can say for certain is that our issue is completely unrelated to those affecting treatments and approvals for SSRIs and depression.

We are not a group of pill-popping casual consumers. We deserve the chance to save our children. Now we just need to get that chance.

Roy Zeighami
Founder, Sanfilippo Foundation for Children

214-901-SF4K (7345)