Lincoln Lewis Wheatley

Lincoln Lewis Wheatley, son of Zachary & Kelly Wheatley, was born into this world on October 24, 2008. Unfortunately, and without anyone’s knowledge, he was also born with Gaucher’s Disease. At about 2 to 3 months of age, Lincoln began to exhibit the start of classical clinical symptoms related to the disease…however, the early symptoms are often common problems, such as cough and cold, poor weight gain, stiffness, etc. Thus, doctors rarely look to something as serious as this disease and for good reason. Hence, this is a primary issue with early diagnosis. With Lincoln, it wasn’t until his little weight gain and chronic breathing issues became too much that doctors started to look at other possibilities. Of course, Lincoln was smiling and happy the whole time, not a care in the world. Every doctor visit, every hospital stay…he was a trooper. At approx. 7 to 8 months of age and after an extended hospital stay, when doctors noticed an enlarging  liver and spleen, it was determined that Lincoln may have Gaucher’s disease. Although very rare, Gaucher’s is part of the larger family of genetic “storage disorders” (closely related to Tay-Sach’s, etc.). Of course, Lincoln’s parents along with all the doctors, were devastated by the news. On July 13, 2009, Lincoln passed away in his Mom and Dad’s arms…very peaceful and quite happy. Although his life was cut short, his time here was very special. He was always happy and his parents know he is smiling down on them right now.

 A New Family Arrives

In February of 1994, a family from California had arrived with their 1-year-old son for their first visit at the NIH. As I interacted with this family that first week I was impressed with their proactive nature. They had many questions – many of which were answered well into the evening hours after a long day of testing. Although I would arrive home late on those evenings, I did not mind because the questions were intelligent and thoughtful. To my surprise, prior to each subsequent visit I would receive from this family a Federal Express package – whereby the questions were sent in advance. Eventually they asked two questions that were very difficult to answer.

1. How is the disease affecting Gregory’s brain?
2. Is anyone doing research to find a cure?

 To the first question I answered “we do not know” and to the second I answered “not really … any serious research”. I knew this was disheartening news, but at the time it was the truth.

 Gregory Passes Away … The CGRF is Born

Greg and Deborah Macres lost their son Gregory to Gaucher disease in April of 1997. I was pleased that subsequent to Gregory’s passing the family continued to stay in touch, and often discussed the possibility of establishing a charity to fund research on Gaucher disease. I was supportive, but withheld my enthusiasm understanding that this family was still coping with the grief of losing a child.

 Thinking back to those phone calls some 12+ years ago I never imagined that this desire, spawned by the devastating loss of a son, would result in the Children’s Gaucher Research Fund and the progress they have made over the past 10 years. The Macres family, and other families from around the country, began raising funds, and in 2001 they found their first opportunity to fund serious research on neuronpathic Gaucher disease. It was in the form of a newsletter I sent to the Macres’s from the Weizmann Institute of Science in Israel. In that newsletter there was a small article written by Dr. Tony Futerman indicating that they had formulated a theory, and his laboratory had a keen interest in investigating their theory as to how the brain is affected in children with neuronopathic Gaucher disease. Prior to this I had not met Dr. Futerman, but that year I visited his laboratory in Israel. I was very impressed with his facility, and to my surprise found that we had similar views as to what might be causing brain disease in these children.

 Ten Years of Work … Ten Years of Progress

Over the past ten years the CGRF has funded Dr. Tony Futerman’s laboratory, resulting in very important research that has been published in nine separate scientific journal articles. Today, the answers to those two difficult questions sited above have very different answers. Because of the efforts of the CGRF we are significantly closer to understanding how the brain is affected, and yes, there is now serious research being pursued. Additionally, the CGRF recently funded the creation of an Inducible nGD Mouse Model; if successful this will significantly advance serious research in coming years.

 Rare Diseases and Families

Often rare diseases do not attract interest or funding, and frequently sit idle for many years with little progress. Over the years however, families have made great contributions to medical research on rare diseases. It usually comes in the form of funding basic scientific research, thus creating the building blocks of understanding. Once these building blocks of understanding are put in place the disease then attracts more interest, and more funding for research. The CGRF has done just this – funding basic science – resulting in publications in scientific journals – sponsoring three international scientific conferences with a fourth scheduled for 2012 – the funding of the Indiclble nGD Mouse that will be available for use by laboratories around the world – links that have been made with some of the 26 other lysosomal diseases that affect the brains in children – the potential connection to Parkinson’s – all  contributing to bringing us further down the road toward a cure.

 Those Two Questions … Now Have Different Answers

Thanks to those of you who support the efforts of the CGRF, the answers to those two questions sited above are markedly different than they were on that day at the NIH; when a mother and father were simply trying to understand how they could best help their son. We believe, because of your support, that the building blocks are in place and that a new phase in nGD research is around the corner.

Dr. Raphael Schiffmann M.D., M.H.Sc. – Director of the Institute of Metabolic Diseases at the Baylor Research Institute in Dallas, Texas, and Chairman of the Scientific Advisory Board for the Children’s Gaucher Research Fund.

“The Independent Charities Seal of Excellence is awarded to the members of Independent Charities of America and Local Independent Charities of America that have, upon rigorous independent review, been able to certify, document, and demonstrate on an annual basis that they meet the highest standards of public accountability, program effectiveness, and cost effectiveness.  These standards include those required by the US Government for inclusion in the Combined Federal Campaign, probably the most exclusive fund drive in the world.  Of the 1,000,000 charities operating in the United States today, it is estimated that fewer than 50,000, or 5 percent, meet or exceed these standards, and, of those, fewer than 2,000 have been awarded this Seal.”

Remember: 100% of your donation goes to medical research.

Jason and Amber Jaynes share their commitment:

“When our daughter passed away we knew that we wanted to do something to honor her and keep her legacy alive. We also wanted to be able to help bring community awareness about the disease our daughter suffered from. With it being such a rare disease many people have never heard of it. We decided to start an annual motorcycle ride in her memory. We have done this the past two years. In doing this event we have reached out to many local media outlets to help us to spread the word.

Our event each year features a motorcycle dice run, a silent auction, a raffle, and selling bar-b-que plates. We have been very blessed with being able to put these events on by 100% donations from the community. Many people in our community are now familiar with Gaucher Disease and my daughter’s story because of these fundraising events. We donate the proceeds to The Children’s Gaucher Research Fund each year. We hope to be able to continue this event every year.”

Read their story – “Sweet Willow”

 First a little background.

I have had the honor of being supported by three research grants from the CGRF over the past decade or so. Each time that I have submitted an application for a renewal of my funding, my knees have trembled! Would I receive an additional award? Do my scientific peers, who independently evaluate my research grant applications, think that progress has been sufficient to merit another award? What would happen to the research on neuronopathic Gaucher disease in my laboratory if the work was not funded? Fortunately, I have been privileged to receive funding, with the most recent round of funding being awarded towards the end of 2010, for a period of three years. And for this I express my thanks, not only to my scientific colleagues who rated my research as worthy of funding, but also to the CGRF and its generous and committed donors.

 How much money is needed for research?

Some of you may be wondering why so much money is needed for scientific research (for your information, the grant which I was just awarded is worth $100,000 per year for three years). Well, research is very expensive. A major expense, and perhaps the major expense, is personnel. I currently have two outstanding graduate students, studying towards their PhD degrees, working on the CGRF-funded projects. Another major expense is laboratory supplies – from simple chemicals to the specialized tools needed to perform technically-demanding aspects of the research. And then there is the cost of international collaborations, of which we have a number. So although the sum awarded to my laboratory may sound like a large sum, every cent is needed to push the research forward.

 How long does research take?

Another question that I am sometimes asked is why it takes so long to discover the causes, and the biochemical mechanisms that cause neuronopathic Gaucher disease. After all, the disease has been known for decades, there is an excellent therapy for type 1 Gaucher disease (that is, the form of Gaucher disease that does not affect the brain), and surely there are hundreds of researchers working on neuronopathic Gaucher disease all over the world? These are all good and relevant questions, but the answers may surprise you. First, even though the genetic cause of Gaucher disease is known, and has been known for decades, the biochemical question of why specific areas of the brain are affected in Gaucher disease, and not others, is simply unknown, as is the reason that some patients develop brain symptoms whereas others do not. As for therapy, I am sure that I have no need to tell any of you that Cerezyme (enzyme replacement), which is used for type 1 Gaucher disease patients, is simply ineffective in the brain since it cannot cross the blood-brain barrier. And finally, and this might be really surprising, but there are actually very few research laboratories working directly on neuronopathic Gaucher disease – one of the reasons for this is that the disease is very rare, and there are limited sources of research funding available from international and federal research funding agencies. This is of course where the CGRF comes in – having recognized the need to support research, the CGRF has pushed ahead and made research possible, at least in my laboratory. Moreover, funding by the CGRF has enabled us to establish a number of important collaborations with leading research laboratories all over the world.

 New researchers involved

One other point before I get into the nitty-gritty of my research. I actually foresee a significant increase in the involvement and recruitment of new researchers into the neuronopathic Gaucher research area. In January 2011, I had the honor of chairing the first ever Gordon conference specifically devoted to the study of lysosomal storage diseases – for those of you not in the know, Gaucher disease belongs to a family of genetic diseases known as lysosomal storage diseases, and 180 researchers and students gathered together in Galveston, Texas, to discuss the latest advances. You should also be aware that Gordon conferences are considered the premier research conferences in the world, and the fact that the Gordon conference organization saw fit to sponsor this new conference provided significant new momentum for the field in general. The discussions at the conference were lively, and based on the large numbers of discussions that members of my laboratory had with other participants, I believe that issues related to understanding the pathological mechanisms at play in neuronopathic Gaucher disease will be pushed to the forefront of lysosomal disease research in the coming years. The importance of Gaucher disease research will also be strengthened by the recently-discovered genetic relationship between some forms of Gaucher disease and Parkinson’s disease. This is not the place to go into this issue in any more detail, but the neuroscience community is much more aware of neurological aspects of Gaucher disease than they were even five years ago. This has to be good for the research field.

 My research

Let’s now get down to some of the details of my research. When I was first funded by the CGRF, we had demonstrated an important connection between changes in calcium levels and the death of nerve cells – this research is all published, and you can find links to the work via the CGRF web page (www.cgrf.org). Suffice to say that all of this work was performed using cultured cells, that is to say, nerve cells which we isolated from mice (or rat) brain, and grew in a culture dish in an incubator. The reason we worked on cultured cells, rather than on more advanced models, was because no advanced models were available. This has changed recently, and our research will now be able to address areas that could not have previously been tackled.

 A mouse model is generated

A huge breakthrough came in 2007 when Dr. Stefan Karlsson, in Sweden, generated a mouse model of neuronopathic Gaucher disease. A mouse model is basically a genetically-manipulated mouse that resembles, to some extent, a human disease, and allows issues to be examined that could not be studied otherwise. For instance, new therapies are invariably tested first on mouse models of human diseases, before they can be tested on human patients. Dr. Karlsson generously made his mouse available to researchers worldwide, including to my laboratory. Now that we had this mouse, we were able to pursue research directions that had been impossible beforehand. For instance, Einat Vitner, one of the two graduate students currently supported by the CGRF, was able to show changes in levels of a molecule called ‘cathepsin’ in the brains of the mice. The release of cathepsins from cells in the brain is consistent with a model of brain dysfunction known as neuroinflammation, which interestingly, has been shown to occur in a number of other lysosomal storage diseases. Another research area was to examine which specific areas of the brain were affected in the mouse. This study was performed by the other graduate student, Tamar Farfel-Becker, who defined, for the first time, the progression of some of the neuropathological changes. Remarkably, she found that some areas which are affected might be able to provide an explanation for some of the symptoms found in children. For example, an area known as the substantia nigra reticulata was affected, and this area is known to play an important role in some of the eye movement problems observed in children (for those of you really interested in this work, it was just published in the distinguished journal, Human Molecular Genetics). These examples of some of our results lead me into a discussion of what we are planning to do over the next two and a half years of our funding.

 Three major research areas

We are working on three major research areas. First, we want to understand why certain areas of the brain are affected in the disease, and of no less importance, why certain areas are not affected. If we could understand this, we might be able to make predictions about the kind of therapies that are needed. Second, we want to understand the process that I mentioned above, namely neuroinflammation, in disease progression. As I also mentioned, neuroinflammation has been observed in a number of other brain diseases, and also in other lysosomal storage diseases, meaning that lessons learned, and tools available from some of these other studies might be applicable to neuronopathic Gaucher disease. Finally, we want to take advantage of the two goals above to try to discover new therapeutic options. For instance, there are many common drugs that can be used to treat neuroinflammation – might these be useful to ameliorate disease symptoms in the mouse, and then possibly in humans? I should say that so far this approach has not been successful in the mouse that we received from Dr. Karlsson – however, there is a caveat in the use of the Karlsson mouse inasmuch as it only lives in the laboratory for a relatively short period (2-3 weeks), meaning that the window of opportunity for treatment is fairly limited.

 A mouse is a mouse – NOT REALLY

This is one of the reasons that the CGRF has also funded attempts by myself and two colleagues in the Weizmann Institute, who are experts in mouse genetics, to make a new mouse model. I am unable to go into detail at this stage, but I am confident that we will have something exciting to report soon.

 Is there cause for optimism?

So this is where we are to date. Is there cause for optimism? Yes. New researchers are being attracted to the field. One mouse model is available and others are on the way. Neuroscientists are becoming interested in Gaucher disease research. Links are being found between Gaucher disease and other lysosomal storage diseases, and also Parkinson’s disease. Are we close to finding a cure? Well, certainly nearer a cure than a few years ago, but much more basic research is still required before therapies will be available. How long will this take? And to that question, I must honestly say that we have no idea. Scientific discoveries normally occur due to the right environment being established for ideas to develop and come to fruition, and due to funding being available to put these ideas into practice. I can only say that my laboratory is doing its utmost to understand what is going on in the disease, and to take these findings along the path that will lead to a cure. And none of this would be possible without the wonderful support of the CGRF, and for this I express my deep gratitude.

When I went for my 36 week checkup the doctor sent me for an ultrasound because my blood pressure was extremely high.  She came back into the room very concerned because something was not quite right with the baby’s liver.  I was then sent to the local hospital to see a specialist.  He confirmed that something just wasn’t quite right and determined that I should not give birth in Jackson, but rather deliver in Memphis where I was close to LeBonhuer.  I was scheduled to see a specialist in Memphis on Monday August 10, 2009 the day before my birthday, and 3 weeks before my due date.

We arrived at the specialist office and he took several ultrasound pictures himself.  After viewing the results he came into the room and informed me that Willow would be born that day.  After the C-section the first glimpse I got of my daughter she was in an incubator being rushed to the NICU.  She was Polk a dotted all over her body and her abdomen was extremely large.  We spent 9 days in the NICU there and my husband, family, and friends were all very worried about Willow.  She seemed to be doing well but the doctors could not figure out the exact cause of the dots or why her abdomen was enlarged.  Day after day her spots began to fade and the doctors were running test after test and could not figure out what was wrong with her.

On our 9th day there her team of doctors approached me and informed me that we were being transferred to St. Jude because they thought she may have leukemia.  My world came crashing down.  Surely this beautiful gift from God could not have such a horrible disease.  We were transferred to St. Jude, our first day their Willow who was 10 days old was taken for a bone marrow biopsy.  This included Willow being put to sleep and the doctors drilling into her little hips to extract marrow to test for Leukemia.  The test came back negative and we were so positive that this was something she was going to outgrow.  However her liver and spleen were enlarged and her blood test continued to show low hemoglobin and low platelets.  She was hospitalized twice more for bone marrow biopsy’s and once for a skin biopsy.  The 3rd time she was tested I received a call not long after on February 6, 2010.  Her doctor informed me they had figured out what was wrong with her and that it wasn’t Leukemia but a disease called Gaucher’s. I was so thankful it wasn’t cancer until I came home and googled Gaucher’s. I learned that Gaucher’s was a horrible mean disease that hardly any infants or babies survived.

We were transferred to a specialist who tried to help us understand the disease a little better and tried to determine the best course of treatment for Willow.  She had not ever seen an infant that had presented with symptoms before birth and had to consult some colleges before deciding her treatment course.  After our first visit with the genetics specialist Willow became very ill and we were admitted to LeBonhuer.  We wound up spending a month their and during that time many other horrible problems caused by Gaucher’s were uncovered.  

We came home with a central line and Willow not being able to eat anything by mouth. She was hooked to an IV for 17 hours a day.  We began enzyme replacement therapy while at the hospital and she continued to receive it once a week.  She spent the last 4 months of her life at home with her loving family.  On her 1st birthday we woke to find she had passed in her sleep.  We were devastated; our worst fears had come true.  Each day is a struggle but I know our beautiful daughter is without sickness in the arms of our Lord.  She has taught us so many things that without her we never would have understood.  She has made my husband and I better people.  I am grateful for our time together here on earth and hope I will be reunited with her one day.

Amber and Jason Jaynes

Jackson, TN

Our family chooses to live in the present.  The could have, would have, should have’s in respect to doctors and how this journey unfolded is counterproductive.  We feel Emily’s diagnosis was found exactly when it was supposed to, and leave the unknowns to the Universe.  I hold hope for Pediatrics to integrate the knowledge of genetic disorders as a possible indication for any abnormalities in their patients, additionally to look outside the box with the understanding that every child is unique and does not present the exact same symptoms.

One day at a time, one moment at a time, is the approach we adopt here in NJ.  When my thoughts seem to stray off course, Emily reminds me the importance of keeping a clear focus on the present by singing he favorite chant “Happy Sun Heart”.

Carla Rose Schiavone

visit our website/blog @ www.caringbridge.org/visit/happysunheart/mystory

 Click Here to Sponsor the Macres Heaven Birthday Ride - in the comment section write “Heaven Birthday Ride”

Diagnosed December 1993

Greg Macres, Gregory’s father and Co-founder of the CGRF, will begin his 41-mile memorial bike ride around the South Bay area in Palo Alto on the steps of Greg’s boyhood home. He will then ride to Kaiser Hospital in Santa Clara, where over a four year period Gregory received treatment for Gaucher disease, for both routine and emergency services. From the hospital Greg will then ride to Saratoga Presbyterian Church where, in 1997, over 400 friends and family gathered at his memorial service to honor his life. The next stop will then be in San Jose, to the site where Gregory was laid to rest.

Tests at National Institutes of Health

 At his resting place, Greg will join Deborah and Gregory’s brother and three sisters to share stories and reflect on Gregory’s humor, his resilience, and his courage. It will be a celebration of his life, knowing that the legacy of his fingerprints are paving the way toward a cure for children with Gaucher disease.

“This first annual Macres Memorial Heaven Birthday Ride is our family’s way to support the CGRF’s efforts toward finding a cure for these children. We would be honored if you would consider sponsoring this special event.  We thank you in advance for your support.”

Bone Marrow Transplant, 1997

 100% of Every Donation Goes Towards Medical Research.

Despite life's challenges - Always a Smile

This was the commitment made by the founders of the CGRF (Greg and Deborah Macres) when the fund was initiated shortly after Gregory’s memorial service. Since that time over $1.7 million has been raised and important medical research has been funded. This is a long road to travel – the CGRF has chosen to travel this road – and the road to a cure is paved by your generous donations.

Your continued support is greatly appreciated.

The use of twelve reviewers is perhaps excessive, however we take seriously the generosity of our donors and we strive to ensure that every dollar of research is spent wisely. Each reviewer is asked to rank each proposal between 1 and 10 (with 10 being the highest recommendation) and to include specific narrative comments to support their ranking. An overall ranking of 7 and above will be considered for funding, however to date the CGRF has only funded research proposals with an overall average ranking of between 8 and 10.

Tony Futerman Ph.D. Weizmann Institute of Science, Isreal

The highest overall average ranking was received by Tony Futerman Ph.D. of the Weizmann Institute of Science in Israel. The CGRF has awarded this research laboratory a $300,000 research grant to pursue the “Pathophysiological Mechanisms in Neuronal Forms of Gaucher Disease”.

Below are comments submitted by one of our esteemed reviewers:

“This grant builds upon a previous body of research funded by CGRF that has delivered excellent value for the money and multiple [scientific] publications. This is the best of the basic science proposals this round. The aim is to generate insights into differential neuronal pathology and its mechanism(s), probe the involvement of neuroinflammation in neuronopathic Gaucher and test new therapeutic approaches based on the two main aims. The previously CGRF funded inducible mouse model of neuronopathic Gaucher will feed into this research program nicely as it will be available within 12 months. The comparative analysis of the acute Karlsson mouse and the new mouse will no doubt lead to important mechanistic insights into pathogenic mechanisms, leading to new therapeutic approaches that can be tested in the two models. All the proposed studies are important, logical, based on sound preliminary data and building on a proven track record of productivity. All the studies are well within the capabilities of the lab.  I think it is important to keep neuronopathic Gaucher disease research a focus of the Futerman lab and to continue the funding of what has been and will continue to be innovative, rigorous and hypothesis driven mechanistic research. New therapeutic approaches will no doubt arise and be tested by this group based on the aims of the grant and their access to proprietary compounds (even if they can’t be disclosed at this stage) is an additional advantage.”

The Children’s Gaucher Research Fund does not have the ability to fund all 11 research proposals some of which were quite compelling. However, we are taking a closer look (continuing to review) one other compelling proposal with the potential of funding a portion of or the entirely of the grant request.

In years past the CGRF has released similar “Calls for Research”, however the response in 2010 has far surpassed previous interest. This is a testament to the fact that science is accelerating – more is being learned about these brain diseases in children – and more scientific laboratories have an interest in pursuing avenues that may lead to a cure.

These advances in medical science are compelling, and it gives the CGRF further motivation to continue in our quest to raise funds to support this important research. It is your donations that fund this important research – donations can be made online at www.childrensgaucher.org.  We truly appreciate your continued support.

100% of donations received by the Children’s Gaucher Research Fund go directly to Medical Research.