Tag Archives: BioMarin

October 24, 2012 · 4:29 pm

Placebo study could impact PKU clinical drug trials

Findings from a study published in the Oct. 23 edition of PLOS ONE, a peer-reviewed online scientific journal, suggests that people with a gene variation that leads to higher dopamine levels in the brain respond better to placebos than those individuals with low dopamine levels.

The science, health and technology news website LiveScience reported on the study and described how researchers tested to see whether a person’s genes can control a placebo response:

PKU, Phenylketonuria, Gene Mutation, Gene Variance, PKU Clinical Trials, Placebo

“To find out, Hall and her colleagues analyzed DNA from 104 patients with irritable bowel syndrome who were randomized to one of three groups: One was told they were on the waiting list for treatment, another received a placebo in the form of seemingly real, curt acupuncture, and the third group received fake acupuncture from a caring, warm practitioner who looked patients in the eye, asked about their progress, and even touched them lightly, Hall told LiveScience.

Patients with the high-dopamine version of the gene felt slightly better after seeing the curt, all-business health-care provider that gave placebo acupuncture. But they were six times as likely to say their symptoms improved with a caring practitioner as those with the low-dopamine gene, who didn’t improve much in any group.

The findings suggest that medical studies called clinical trials could identify treatment versus placebo effect by grouping patients by gene variant, Hall said. Knowing up front the level of placebo effect for a clinical trial could reduce the cost of the trial significantly by using fewer participants, for instance, she said.”

How does this relate to PKU?

PKU patients have very little or no phenylalanine hydroxylase (PAH), an enzyme in the body that converts phenylalanine into tyrosine. Tyrosine is used by the brain to synthesize dopamine, an important neurotransmitter involved in motor functions and mood. This means that PKU patients, especially those “off-diet” or those not regularly consuming formula, will experience relatively low levels of dopamine. This is the reason that some of the side effects experienced by PKU patients on an uncontrolled diet can include anxiety, depression and other mood disorders.

No doubt, it will be interesting to see whether these new findings will have any impact on how BioMarin or other pharmaceutical companies will structure future PKU clinical trials. Researchers will have to consider whether having a mixture of on-diet and off-diet PKU patients randomly assigned to control and experimental groups will have any bearing on the trial’s accuracy. Or perhaps a closer look at the specific gene mutation that allows some individuals to operate with higher dopamine levels will someday provide answers for how to increase dopamine in those of us who could benefit from a little more.

–NM

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August 3, 2012 · 11:23 am

A revamped PKU.com is on its way!

Just this past week, I was fortunate enough to participate in a telephone survey administered by a representative from GA Communication Group, a Chicago-based marketing agency that has partnered with BioMarin for the complete redesign of PKU.com. When I spoke with GA Communication Group, the agency was in the process of interviewing several subgroups of the PKU community including on- and off-diet patients, Kuvan patients, dieticians and PKU parents. The questions not only focused on the ways in which these groups used PKU.com, but there was also a genuine interest behind gaining more understanding into the complexities of receiving a diagnosis, talking about it with friends and family, as well as understanding the mechanics behind tracking and documenting phe intake.

PKU.com screenshot , Phenylketonuria, BioMarin

Pictured above is a screenshot of the current homepage for PKU.com. BioMarin and GA Communication Group have partnered together to redesign the site and hope to launch the new site later this year or by early 2013.

There’s no surprise that a significant portion of the interview delved into the subject of new communication technologies. After all, a lot has changed in terms of the way we seek out and share information through online platforms. For example, when prepping for the telephone interview, I was surprised to learn that I had in fact created a PKU.com user profile when I first stumbled upon the site in 2007. Despite having registered an account, I didn’t actually fill out any of the empty fields under my profile. I speculated to the GA interviewer that in 2007 it was very likely that I was hesitant to put myself out there. Much has changed since then. Not only do I have a Facebook page, but most people I know would think I’m crazy if I didn’t have one!

GA Communication Group and BioMarin plan to wrap-up the research phase of the PKU.com redesign effort very soon. However, it will be several months before the rest of us get to see the final product. Ultimately, I would like to see the new PKU.com have a more user-friendly interface – one that can be easily accessed from any number of electronic devices. I’d also like to see a portion of the site used for communicating current PKU research initiatives. With BioMarin sponsoring this site, I’m not sure how much of a conflict of interest that might present if there are other companies interested in PKU research. Perhaps a strategic partnership with either the National PKU Alliance or some other non-profit organization for managing that portion of content would help resolve that dilemma.

On that note, how many of you regularly visit PKU.com? And if you’re familiar with the site, what would you change about it? I even thought it might cool to incorporate a Skype-like video conference feature so that registered users could chat with each other long distance. Whatever your thoughts are; be sure to submit them in the comments section below. Looking forward to hearing from you!

–NM

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April 6, 2012 · 4:38 pm

Maternal PKU and Sapropterin

This past February, the National Institutes of Health (NIH) hosted a scientific review conference on Phenylketonuria to discuss the “state of the science and future research needs.” The event was free and open to the public, but even if you could not cover the cost of travel and accommodations, the two-day event was also broadcasted live via webcast. I managed to log-on during my lunch break and listened intently to a session on PKU and Pregnancy. To my surprise, much of the PKU and Pregnancy presentation focused on Sapropterin and its use during maternal PKU (Sapropterin is the generic name for Kuvan, the first prescription drug approved by the U.S. Food and Drug Administration to lower blood phe levels in PKU patients).

To be clear, Kuvan is not recommended for maternal PKU unless the benefits outweigh the risks. That is because when ranked on the FDA’s pregnancy classification of drugs, Sapropterin is considered a category C drug since it is still unclear whether Sapropterin crosses the human placenta.

Research presented at the NIH conference confirmed that in some rare instances, Sapropterin had been prescribed to pregnant PKU patients, but only when the woman could not achieve dietary control at the start of her pregnancy. As early as 2005, Sapropterin was the focus of a study led by medical pioneer and PKU advocate Dr. Richard Koch. The patient was responsive to Sapropterin and during her pregnancy, she continued the medication at 40, 60, and 100 mg per day in the first, second, and third trimesters. Used in combination with low-protein food, optimal phe levels were achieved without any nausea and vomiting. More importantly, the woman’s child was born normal. Four years later, another study conducted by one of the presenters, Dr. Gabriella Pridjian from Tulane Hayward Genetics Center, reported on another pregnant PKU patient who had difficulty tolerating low-phe protein supplements. She was instructed to divide the Sapropterin up twice daily and ultimately had a healthy baby delivered through c-section. Pridjian noted that there were plans to eventually formally test the baby (who was now three years old) for any intellectual or developmental issues.

In addition to these two case studies, the NIH panel reported that other pregnancies involving the use of Sapropterin were currently underway. In addition to concerns about whether Sapropterin harms a developing fetus, doctors admitted it was hard to determine if symptoms such as headache, rhinorrhea, vomiting, fever, abdominal pain, rashes or nasal congestion were a result of the prescription drug or simply associated with the pregnancy.

Even though the maker of Kuvan, BioMarin, does in fact encourage pregnant women who were exposed to Kuvan during their pregnancy to participate in ongoing studies about the drug’s effect, there are no plans for future controlled studies. Based on what little has been conducted, including the two case studies I’ve mentioned here, initial reports of using Sapropterin during pregnancy are encouraging. However, continued research on this matter is definitely a must, especially with concern to the long-term implications the drug might have on a PKU woman’s child.

–NM

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March 20, 2012 · 1:56 am

Kuvan Responder Trial: Prepping for a Second Attempt

Since my Kuvan responder trial last August, I’ve had many conversations with BioMarin representatives who say they are not yet ready to “throw in the towel” when it comes to deciding whether I am a responder to the first PKU prescription drug.  The results of my first attempt were determined inconclusive; however, as a PKU patient currently off-diet, my eating habits are certainly more complicated than those folks who normally embark on this journey.

Needless to say, I’ve given the matter much thought and do feel that it might be worth a second go-around with the Kuvan responder trial later this year. A couple things will be done differently though. Here’s a look at some of the changes that will hopefully lead to a more definitive result.

Obtain baseline data of phe-levels prior to Kuvan responder trial—Since my unrestricted diet complicated matters, I am sending my clinic a blood sample and comprehensive food diary once a month in order to establish a baseline phe-level. During my first Kuvan responder trial, I was manually tracking protein using my iPhone’s notepad app. This time, however, I’ve starting using a different, free iPhone app called MyFitnessPal which tracks all sorts of nutritional data including protein. I just completed my baseline phe-level for the month of March. For that day, I had consumed 83 grams of protein and my phe-level came back at 17.6mg/dl. By the time I make a second attempt at a Kuvan responder trial, I should have 4 or 5 of these baseline phe-levels to work with.

Using My Fitness Pal for tracking protein

Left-hand screenshot shows food diary for March 13.
Right-hand screenshot shows nutrient details for all food consumed that same day.

Collaborate hand-in-hand with a Kuvan clinical coordinator—Communication issues and the lack of a well-defined trial process may have impacted the results of my first Kuvan responder trial so I was happy to hear that BioMarin has created a new position called the Kuvan clinical coordinator. This person serves as a liaison between PKU patients who are exploring the use of Kuvan and the metabolic clinics that prescribe it. A quick Google search found a BioMarin job posting which described the new position’s responsibilities as collaborating “with assigned patients to ensure compliance with the clinic’s protocol, assess response to Kuvan therapy, advocate for patient needs, conduct patient-level education, and…to address specific issues and needs that arise following the decision to initiate the Kuvan trial.” I have already met my clinic’s assigned Kuvan clinical coordinator and do feel she will bring some much-needed structure to the process.

Less variation in food consumption—The last adjustment currently being considered for my second Kuvan responder trial is the possibility of eating the same foods and same portions throughout the duration of the trial. As I understand it, this second trial may need to extend as long as three to four weeks. Eating the same breakfast, lunch and dinner for that amount of time might be rather tough, but to help make it easier, one alternative I’d like to explore is re-purposing the food data I’m already tracking in the MyFitnessPal app. That same information can be used to create a list of meal combinations I can alternate between during the trial while still consuming the same approximate amount of protein.

As you can see, preparation is key! It sounds like a lot of work—which is why I am waiting until after grad school to attempt a second time—however, if it works and I am determined to be a Kuvan responder, the benefits can far outweigh a couple weeks of inconvenience.

–NM

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February 19, 2012 · 3:20 pm

Kuvan Responder Trial: Delayed Results Presented and Explained

First let me express my apologies for being away from this blog for so long. I spent the final months of 2011 researching, writing and defending my masters’ thesis. It was a very intense process that consumed any free time I might have had left after also working fulltime as a communications and marketing specialist. I am now in the process of working through my last class at the University of Tennessee and as I edge closer and closer to my May 10 graduation, my focus is once again shifting back towards PKU.

One of the subject areas I left unresolved during my five-month hiatus was the results of my Kuvan responder trial. To be fair though, I had anticipated hearing at the end of the trial a clear yes or no as to whether or not I was considered a responder to the first PKU prescription drug. Instead, my phe levels were all over the place and a number of variables were suspected to have led to the erratic results. Needless to say, I needed to work through some of this confusion before reporting back to my blog followers. To sum it all up in one word, the results were inconclusive. Here’s a closer look at my blood test results:

PKU Kuvan Responder Trial Results DataFor any readers who might need some additional context, I have been told that a person who does not have PKU will normally have a phe level of 0. If that same person just finished eating a meal that is high in protein, their phe level might register at a 1 or 2. However, once the food has been fully digested, the phe level will return to 0. Clearly, from these results, my phe level hasn’t dropped anywhere near safe levels.

In addition to blood tests, I was also asked to track mood or disposition changes I experienced throughout the trial. I will admit that after being on Kuvan for several days, I felt as though I might be slightly more relaxed and getting a better night’s sleep. However, assuming that because I knew this medicine might improve the way I feel, there’s a possibility that these mood changes could also be attributed to the “placebo effect”—the idea that a treatment appears to exhibit results simply because a patient believes it will work.

Ultimately, my clinic recommended I consider a second Kuvan responder trial; this time with more emphasis on controlling some of the variables that might be responsible for the inconclusive results. I haven’t rejected the idea of giving it another shot, but obviously with grad school still in progress, it will probably be several months before I do. During my next post, I’ll take a look at what some of those variables are and also discuss what changes might occur in a second Kuvan responder trial.

–NM

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August 10, 2011 · 6:31 pm

Keeping an Off-Diet Food Diary during a PKU Kuvan Responder Trial

Off-Diet PKU Kuvan Responder Trial Food DiaryWhen BioMarin’s Kuvan was approved by the FDA in 2007 as the first prescription drug to treat phenylketonuria (PKU), directions for taking the prescription drug stipulated that a low-protein diet must also be followed. However, when I first discussed a Kuvan responder trial with my clinic in the fall of 2010, I was advised that I could remain on a non-restricted diet as long as I consume close to the same amount of protein each day. I suspect that this relaxation was granted with the understanding that if I do in fact respond to the drug, then lower phe levels are better than completely unbridled protein intake. They key; however, to making sure that you consume roughly the same amount of protein each day means keeping a very detailed food diary.

Initially, I found it tricky to figure out a good method for capturing my daily protein intake. I explored the possibility of using Cambrooke’s DietWell app—a fabulous tool for the PKU community—but the more I experimented with it, the more I realized that the items that are truly high in protein are absent from its database.

So now that I’m nearly a week into my Kuvan responder trial, just how have I managed to keep track of my protein consumption? Well, here are the three “secrets” to my success:

  1. Take advantage of publicly available information—Obviously, checking a food product’s nutrition label is a great place to start when keeping a food diary. Be sure that the first thing you look at is the serving size because many products you buy in the grocery store will contain multiple servings per container. Use a weighted food scale, measuring cups or measuring spoons to gauge you portions. For times when not eating at home, try to plan ahead. Many restaurants list nutritional information on their Websites, have apps you can download to your mobile device or sometimes you can even ask your server for a printed brochure of nutritional information.
  2. Men’s Health—Whether it’s the New York Times Bestselling “Abs Diet” or the popular “Eat this, Not that” series, Men’s Health does an excellent job of providing all the information you ever possibly want on a food item. I especially like their recipes where we can cook healthy, in the comfort of our own home, and know exactly how much protein there is in a serving size. I’m sure other recipes, whether in a magazine or posted on a popular cooking website, will provide the same type of useful information. The Men’s Health product line has worked very well for me though.iPhone notepad app screen shot Kuvan Responder Trial PKU
  3. iPhone Notepad App—Lastly, because I am getting my protein equivalent information from a variety of sources, I decided to use my iPhone’s notepad application to track my meals. Even though this notepad app came standard on my iPhone, it has the mobile convenience of the DietWell app, but the flexibility of a blank page. I’m able to enter whatever food product I ate, total the daily protein amount, and when I’m done, forward the finished document directly to my email.

–NM

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August 4, 2011 · 12:47 pm

Today’s the Day – Kuvan Responder Trial Begins!

PKU, Kuvan Responder Trial, It's on like Donkey KongBelieve it or not, the phrase “It’s on like Donkey Kong” is listed in the Urban Dictionary and is recognized as a term to express that now is the time to throw down and compete at a higher level. That’s my motto as I embark on the first day of my Kuvan responder trial.

It was just six or seven weeks ago that I announced plans to delay the Kuvan responder trial due to hectic personal and professional activities.  So what’s changed? Not a whole lot. Life is still hectic. I’m still working and going to grad school. But I think I’ve gained perspective. The trial won’t last forever and if I can just make it through the next two and half weeks, then we’re golden!

During the Kuvan responder trial, I am required to keep 6 daily food diaries, take 7 blood samples and consume 13 tablets of Kuvan each morning.

Walgreens a.m./p.m. pill boxTo help juggle all the pills I have to take, I went out a purchased pill box. This one—with its a.m. and p.m. compartments—is pretty convenient since I will take Kuvan in the morning and my allergy meds in the evening. Might seem kind of silly, but its organization and routine that is going to get me through this process. If you’re taking Kuvan and want to get one for yourself, I purchased this one from Walgreens for $9.99.

I’ll check back in frequently to let you know how it’s going. At the end of the whole experience, I’ll report any symptoms, note whether I feel any improvements in concentration or mood, and of course, let you know if I am a responder.

Wish me luck – ‘cause it’s on like Donkey Kong!! :-)

–NM

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July 5, 2011 · 9:15 pm

MRI Scans Helping to Advance PKU Research

MRI Brain Scans

When my husband and I recently attended the Network PKU Conference in Denver, Colo., there was a very interesting presentation given by Dr. Shawn Christ, director of the Clinical Neuropsychology Laboratory at the University of Missouri’s Brain Imaging Center. His research focuses on the brain and why conditions like PKU impact its structural and functional integrity.

After reminding attendees that hi-phe levels can build up and cause damage, Christ explained that he and his team have started using magnetic resonance imaging, or MRIs, to study impact to the brain. The equipment located at the Brain Imaging Center not only uses magnetic fields to generate images of the brain, but is also outfitted with hi-definition projectors and surround sound speakers for conducting visual and auditory memory experiments.

When used on PKU patients, MRI scans can capture any damage that might have been caused to the white brain matter, thus providing a glimpse into the structural integrity of the brain. What’s more though, Dr. Christ has begun looking at the functional integrity of the brain by asking research subjects to solve math problems while undergoing an MRI. Another test the team might use examines memory function by asking participants to watch a series of letters and then push a button when the letter they see is the same as what they saw two letters before.

Dr. Christ performed these tests with six PKU patients (who had elevated protein levels) and six non-PKU patients. He then looked to see what parts of the brain people with PKU are using differently than those without PKU. What Dr. Christ found was that PKU patients were activating specific areas of the brain more than the non-PKU participants. In other words, they were compensating.

Fascinating, huh? Well, it gets better. The research, as it turns out, can be applied beyond PKU. That’s because people with learning disabilities, autism and even schizophrenia will all benefit from research focused on brain structure and function. Here’s a video created by the MU News Bureau that further explains the possibilities:

Research from University of Missouri Brain Imaging Center May Lead to Treatment of a Variety of Mental Disorders from MU News Bureau on Vimeo.

In the future, Dr. Christ hopes to explore why it is that some PKU patients are more affected by hi-phe levels than others. He is also planning to team up with BioMarin to see what happens in the brain when phe levels are dropped using Kuvan treatments.

I’m certainly looking forward to hearing more about the ongoing research Dr. Christ and the other researchers are pursuing at the University of Missouri’s Brain Imaging Center!

–NM

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June 12, 2011 · 7:46 pm

Kuvan Responder Trial Delayed

hectic overwhelmingLet’s be honest, life can be hectic. I regularly put in 40+ hours per week, I’m pursuing my master’s in public relations, I try to make it to the gym every now and again, and tonight, I just finished vacuuming my condo from head to toe so that I can finally reclaim my house from all the hair that my two cats have left behind. Let’s not forget the laundry, grocery shopping, and the occasional wedding or baby shower. Honestly, it sometimes feels like I barely have time to hang out with my husband.

What I’m trying to get at here is that last week, when I was supposed to begin my Kuvan responder trial, I started to feel a little overwhelmed. The thought of having to record every single thing I’m going to consume for the next three weeks does not appeal to me in the least. In addition to recording all foods, I also need to make sure that the amount of protein I consume one day does not vary drastically from the next. This takes some thought, some foresight and a whole lot of preparation. What’s more, because I’m currently off-diet, a lot of the foods I regularly eat, which are high in protein, are not included in the wonderful food lists, cook books, and software applications that are specially created for a low-protein diet.

To the rest of the PKU community, all this recording, measuring and weighing doesn’t sound that abnormal; however, with my life unfolding at break-neck speeds, I venture to guess that my non-PKU friends and family are wondering how I’ll even find the time to add this to my plate. The simple answer is you have to make it work, and, eventually, I will. Yet, for now I think there is some value in acknowledging the frustrations and hesitancy I have in getting started on the responder trial. Perhaps there are other off-diet adults considering Kuvan who can benefit from my ramblings, or maybe writing about the experience will turn out to be cathartic. Nonetheless, I intend to work through it and find some ways to make it more manageable.

USDA logoOne such way is that I believe it would be helpful to have access to equivalency data for foods that are high in protein. What I mean by that is this: where can I find information that tells me that the protein found in 4 ounces of chicken is equal to X-ounces of ground beef? I spoke with my clinic about my questions and I was directed to the U.S. Department of Agriculture’s (USDA) National Nutrient Database. Unfortunately, I found the site cumbersome to use, so I continued to conduct some online research. I eventually came upon a meat and protein chart maintained by Dr. J. D. Decuypere, a chiropractic physician with a nutrition background. According to her site, the doctor uses the same data provided by the USDA, but in my opinion, displays it in a more user-friendly format. My clinic also said that in general, 1 oz of meat is equal to 7 g of protein.

Hopefully, this information will help me feel more confident in tackling a responder trial. I’ll certainly continue to keep you posted. For those other off-diet PKU patients out there who took the Kuvan trial, how did you manage the process?  Did you figure out any tricks for making it easier? Share your thoughts in the comment field below. I’d love to hear from you!

–NM

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June 5, 2011 · 11:26 pm

Starting my Kuvan Responder Trial

Kuvan LogoUp until four years ago, the only method for treating people with Phenylketonuria (PKU) was the low-protein diet. I remember being a young girl and my mother telling me that the second there was a cure, she would immediately sign me up. Nowadays, we still don’t have a cure, but we do have the first prescription drug for the treatment of PKU. It’s called Kuvan and it was developed by a pharmaceutical company called BioMarin. Here’s a brief video clip from the U.S. Food and Drug Administration announcing its approval.

Unfortunately, Kuvan doesn’t work for everyone, so before you can receive a prescription, you are required to go through trial to see if you actually respond to the medication. I will be starting my Kuvan trial this week and here’s how it breaks down:

PKU Kuvan Responder Trial

  • I should be receiving my package of Kuvan on Monday (that’s tomorrow)
  • Then on Thursday, I’ll start keeping a very specific food diary (notepad icon). I’m not yet on the low-protein diet, but my clinic advised that as long as I consume close to the same amount of protein each day then we should be in good shape. Otherwise, it would be impossible to tell if Kuvan was working or if I just ate less protein.
  • In addition to the food diary, I also have to take 7 blood samples (red circles). The blood work is pretty intensive in the beginning, but that’s to make sure we get a good baseline reading.
  • Then about three days into the trial, I’ll start taking my Kuvan (yellow circles). The number of pills you take depends on your body weight. I was prescribed to take 13 pills. I need to take Kuvan at about the same time every day and with food since it is acidic and can cause stomach problems.

At the end of the trial, we should know whether I have responded to Kuvan or not. I have some concerns about possible side effects, some of which can be very serious, and I haven’t made any final decisions whether I will take Kuvan even if I am a responder. I am confident that I will not take Kuvan during any pregnancies. Nonetheless, the more information I have, then the better my decisions will be.

Stay tuned and I’ll let you know how it goes!

–NM

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