October 2003 Update


This update details how The Stop ALD Foundation is successfully continuing to take an entrepreneurial approach to Adrenoleukodystrophy (ALD) and Adrenomyeloneuropathy (AMN). In this update we will cover how we continue to drive forward on our three main focus areas:

  1. Therapy development
  2. Awareness
  3. Prevention

We continue to make progress and leverage our funding and resources to amplify and magnify dramatically the donations from the generous people and organizations that have funded the Foundation to date. We continue to need your financial support to drive forward in our efforts and save the children and adults devastated by this horrific and rare disease.

Please feel free to contact us if you have any questions concerning this update. Our contact information can be found by clicking on Contact Us at our web site www.stopald.org. You can also call 713.756.3232 or write to us at:

The Stop ALD Foundation
500 Jefferson Street, Suite 2000
Houston, Texas 77002-7371


Gene Therapy

Gene therapy has been a top priority for The Stop ALD Foundation since its inception. Since the discovery and description of Adrenoleukodystrophy in 1910, a comprehensive understanding of the disease process has eluded scientists. At the dawn of the new millennium, the role of very long chain fatty acids (VLCFAs), the metabolite that is abnormally high in individuals with a defective ALD gene, has yet to be determined. The reason one patient gets one form of the disease at a particular age versus another patient getting an entirely different form is completely unknown. While The Foundation fully supports furthering knowledge in these essential areas, searching for therapies the only way to help patients is The Foundation's top priority.

One important piece of the puzzle that has definitively and uniformly been determined is that all patients afflicted with ALD have a defect in the ALD gene. Therefore, in an effort to take advantage of the recent explosion of knowledge and technology in molecular biology and genetics, the simple yet elegant notion has arisen that would employ inserting a correct copy of the ALD gene DNA which codes for the ALD protein. Early work performed both in cell cultures and in mice has shown that this approach demonstrates meaningful promise as a potential therapy for patients.

The last Stop ALD Foundation update reported that the Foundation had secured the partnership of the biotechnology company, Cell Genesys, which is headquartered in California. While Cell Genesys made huge advances in this project, the company had to respond to the economic climate by narrowing its therapeutic focus during the first quarter of 2003. While this is certainly disappointing news, The Foundation is now in negotiations with the company as well as with various leading investigators in the U.S. and Europe to establish a new series of partnerships. The Foundation will be able to take advantage of much of the hundreds of thousands of dollars of investment already made by Cell Genesys on behalf of this project; it is simply a matter of filling in the gaps in the most efficient and productive ways possible.

Part of the reason Cell Genesys shifted its focus was the perceived climate shift that occurred in response to an adverse event encountered in a French SCID (bubble boy) gene therapy trial. Although the vast majority of treated children were effectively cured from this often-fatal disease, two of these boys now are battling leukemia, so far successfully.

In immediate response to this issue, The Foundation took a very proactive stance. Foundation action included a private meeting with the director of the division in the Food and Drug Administration (FDA) responsible for gene and cellular therapy. In that meeting, The Foundation stressed the importance of advancing the gene therapy agenda in diseases, such as ALD, which are so devastating. The meeting was extremely positive and productive and The Foundation firmly believes that the FDA is receptive to innovative therapies such as gene and cell therapy for deadly and rare diseases like ALD.

Multiple representatives from The Stop ALD Foundation attended and participated in several FDA and National Institutes of Health (NIH) meetings held in Washington, DC to ensure that progress in gene therapy continues. The meetings and participation worked. The FDA allowed research to continue.

The Stop ALD Foundation's gene therapy project is ongoing. Critical pre-clinical work is being conducted at laboratories in France and the U.S., all of which is necessary prior to opening the clinical trial for humans. As a result of the Foundation's work, this project continues to receive very strong encouragement from many sectors, including the FDA, NIH, the French INSERM (the equivalent of the U.S. National Institutes of Health), AFM (a very influential and well funded group that is the French equivalent of the Muscular Dystrophy Association) and leading ALD research institutions in the U.S and France. We have also been fortunate in securing the participation of the leading investigator from the French SCID trial, a dedicated researcher of international acclaim.

To ensure that the Foundation can get to human trials as quickly as possible, during this past American Society of Hematology meeting (ASH) in December 2002, The Foundation's Chief Science Officer secured the collaborative support of a research team that has one of the very few groups of monkeys that have been transplanted with cells containing the gene therapy vector quite similar to the one The Foundation proposes to use in the ALD clinical trial.  This monkey colony was created for other research purposes.  In clinical trials, the issue of safety comes up as well as efficacy.  And quite naturally, people are often quite interested in results obtained in larger animals than mice. Non-human primates fit this interest.  This is a reasonable question for the anticipated ALD gene therapy trial.

When the opportunity arises to study central nervous system tissue in these monkeys, The Foundation will help to ensure that the analysis takes place.  When the original monkey experiment was conceived these scientists weren't interested in brains, let alone ALD. Now The Foundation has made a major inroad into this path of animal subjects animal subjects that are extremely costly and thus very limited in number and hard to come by. Once again, the Foundation has leveraged your funding and gotten another already funded research team interested in ALD and willing to help us to find a cure for ALD.

Mesynchymal Stem Cell (MSC) Therapy

The Mesynchymal Stem Cell (MSC) Therapy project involves scientists and physicians from St Jude's Hospital (Memphis, Tennessee), Children's Hospital of Philadelphia, Tulane (New Orleans, Louisiana), and leading researchers and physicians in Germany. This experimental therapy involves the use of MSCs taken from the bone marrow of adult donors. The MSCs would be delivered into the blood and brains of ALD patients who are at an advanced ALD stage. In the first phase trial of MSCs, these stem cells would be used in conjunction with conventional bone marrow transplants.

The theory is that these MSCs can start halting and repairing disease damage rapidly while the full bone marrow transplant takes effect. These patients are not suitable candidates for traditional bone marrow transplants due to the advanced state of their disease. These are advanced-stage ALD patients who are running out of time and cannot afford the typical 6 - 18 months it takes for a bone marrow or cord blood transplant to halt ALD disease progression. This time lag would either lead to very severe physical and mental debilitation (i.e. rapid progression to a vegetative state) or death. This unique therapeutic endeavor involving MSCs would allow for rapid and immediate delivery of donor cells to the brain the ultimate destination of importance in an ALD patient, with the hope that the positive impact on the disease can thus begin much sooner. Meanwhile, the traditional bone marrow or cord blood transplant is undergone in conjunction with the experimental therapy in order to take advantage of the well-recognized longer-term benefits of these types of transplants. The MSCs would come from the same donor as the bone marrow used for a bone marrow transplant.

In December 2002, in conjunction with the American Society of Hematology (ASH) Conference in Philadelphia, The Stop ALD Foundation hosted a workshop for all key MSC therapy participants in order to review the project. Many details were discussed and everyone agreed on what they need to do to move forward. Today, the work is moving forward in creating the MSC Phase I clinical trial protocol documents and we expect that it will be submitted to the FDA in 2004.

Up-Regulation of ALDR:
A Gene Very Similar to The ALD Gene

The human genome was sequenced, almost in its entirety, some three years ago. The successful sequencing produced myriad findings about human DNA. One is that some human genes overlap in their structure with others. It is almost as if some genes are incomplete or slightly inaccurate tracings of others. These genes are termed homologues.

Recent evidence suggests that the gene most homologous to the ALD gene (which is also known as ABCD1) may have a somewhat overlapping function. This homologous gene is called ALDR or ABCD2.

The protein of the ALD gene is either nonfunctional or not produced in someone with ALD; however, that person's homologous genes, such as ABCD2, function properly. That being said, these homologous genes are only producing at normal capacity which is not enough to make up for the original ALD genetic defect. Recent laboratory experiments have demonstrated that if one were to over express the ABCD2 gene so that there was a super-normal level of that gene's activity, it may have an impact on the course of ALD. When a gene produces a higher level of protein, which is the same as over expressing the protein for which it codes, this is termed up-regulation.

So the question arises: How can the ABCD2 gene be manipulated to be up-regulated in a safe yet effective manner? Researchers know that different drugs have direct impact on the activities of various genes. In both the public and private domain there are thousands of compounds that have only been examined in a narrow fashion. The drugs that are being investigated or even being currently used to treat, for example, acid reflux, are not also analyzed to see if they have a specific impact on any one particular gene out of the 35,000 genes. This is called cross-use. One well known example of cross-use of a drug is Viagra. This compound was originally examined for cardiovascular purposes. Its effect on male impotence was initially regarded as a side effect. Ultimately this effect became the primary indication for use of the drug.

It is highly possible that given the incredibly vast quantity of pharmaceutical compounds that have been both discovered and created over the last 100+ years, that drugs may already exist which may have the ability to up-regulate a particular gene of choice. In the case of ALD, one gene of choice would be the homologue referred to earlier  ALDR. This research entails very sophisticated and very costly screening methods. In this effort, The Stop ALD Foundation has gained the cooperation and support of one of the worlds leading pharmaceutical companies, GlaxoSmithKline (GSK). After numerous meetings in the US and Europe, as well as discussions between The Foundation, GSK, and leading researchers in the field, an organized methodology was agreed upon. Certain compounds will be evaluated in a leading laboratory in Vienna, Austria headed by a world-renowned scientist, Dr. Johannes Berger, while another category of compounds will be further investigated by a leading research institute in Strasbourg France headed up by another internationally acclaimed researcher, Dr. Jean Louis Mandel. Since these are all laboratory experiments, The Foundation expects that data will begin to emerge over the next few months that will help to further refine and target ongoing research. This is a classic Stop ALD Foundation strategy: put all the potential contributing parties together, ultimately resulting in an efficient and directed series of scientific collaborations.

Adrenomyeloneuropathy (AMN):
Following All Leads

The Stop ALD Foundation continues to investigate potential therapies for Adrenomyeloneuropathy (AMN). AMN is the name used when ALD manifests itself in adulthood. While the Foundation is not currently involved in any AMN clinical trials, the Foundation actively discusses this form of the disease at all scientific meetings it attends always looking for new ideas and potential therapies. We are in contact with leading AMN researchers in the US and Europe and are following up on their trials and seeing how we can assist them in moving forward.


Umbilical Cord Blood for Transplant in ALD Patients

Umbilical cord blood used in transplantation already has a proven track record of saving lives. The Stop ALD Foundation continues to educate patients, family members, and physicians concerning the pros and cons of cord blood. Sadly, many physicians are unaware of the effectiveness and viability of umbilical cord blood transplantation as a therapy for ALD patients who are not yet severely affected. Umbilical cord blood should be considered as an option for certain candidates. To learn more about the pros and cons of cord blood transplantation and how it compares with bone marrow transplantation, please see www.stopald.org/ald/currenttherapies.asp

In support of cord blood as a stem cell transplantation option, members of The Stop ALD Foundation have testified before the US Senate and at FDA advisory meetings, concerning a new bill being introduced that would provide funding for a US National Cord Blood Bank Network. This funding and network would increase and sustain the number of cord blood units available for transplant in diseases that would include ALD. Thus, no patient will be declined and delayed having a transplant due to a lack of suitable donor cells. Unfortunately, today, this is an ongoing reality with tragic consequences.


Screening Newborn Babies for ALD

Today every state in the US has mandated newborn screening for all newborns, however, that mandate can be for screening for as few as two diseases (Phenylketonuria (PKU) and Congenital Hypothyroidism). A few states mandate screening for up to 25 diseases. Mandated testing is on a state-by-state basis. Neo Gen Screening, Inc. (www.neogenscreening.com, phone 866-4-NEOGEN, from outside the US call +1.412.220.2300) currently offers a reasonably priced supplemental newborn screening test (less then $100) that screens newborn babies for dozens of rare diseases. Currently, that test does not include screening for Adrenoleukodystrophy (ALD). Neo Gen Screening is refining new technology that would enable ALD to be included in the test. Inclusion of an ALD test would raise the cost of the test by only one to two dollars. Neo Gen Screening is hopeful that their new newborn ALD test will be validated and ready for market by the end of 2004.

Many people mistakenly think that all newborn babies are screened for a large variety of rare diseases where early detection can save lives. Unfortunately, due to the way that the U.S. healthcare system works, the comprehensiveness of such testing (and the diseases screened for) varies widely, and families are often completely unaware of the level of screening performed on their newborn. Part of the reason that such testing is not comprehensive is that the cost involved is an expense which is not immediately recouped by the hospital or medical center where the baby is born. Even though insurance might pay for the bulk of the expenses related to having a baby, such expenses at one institution could include a post-natal screening for 45 diseases while at another institution they may only include a screen for two or three diseases. In spite of this, comprehensive post-natal testing is not even offered to new parents as an option for which parents would have to pay a small additional fee (less then $100).

Currently, if parents want to be certain that their newborn baby is screened for a wide variety of diseases, they must first check with the hospital where the child was born about what screens have already been performed and then contact a company such as Neo Gen Screening to begin the supplemental testing process. The testing company will send out a testing kit that parents take to their pediatrician. A small blood sample is taken from the baby and the kit is sent to the testing company for processing. Parents then get the results from the company. The cost for this supplemental testing is around $60 which includes the testing kit and processing fee. As well, there would be charges from the medical professional for drawing the blood sample.

Comprehensive post-natal testing is highly recommended because of the knowledge gained about the possibility of a rare disease surfacing in a newborn baby's life. For many of these diseases, including ALD, early detection, before clinical signs appear, can dramatically improve the chances of successful therapeutic intervention.

Screening for ALD is not mandated by any state, and the prospect that an ALD screen will be included in a post-natal test does not necessarily make it any more likely that such a test will be required by states.

The Stop ALD Foundation has initiated a dialogue with Dr. Michael Watson, Executive Director of the American College of Medical Genetics (www.acmg.net). Dr. Watson currently heads a federal committee of genetics experts mandated to advise the US government on neonatal screening for a wide variety of disorders. The Foundation's goal is to have ALD included in the list of diseases for which all newborns are screened. Thus, once the screening technology is in place, families and their children will not have to suffer the tragic consequences of facing an unsuccessful battle with ALD strictly because the disease was diagnosed too late. To help reach this goal of making sure that all newborn babies are screened for ALD, the Foundation made a highly scientific and very detailed submission(www.acmg.net/surveys/NBS-05_22_03/nbs.asp) to Dr. Watson which will be incorporated into the development of a critical decision making tool. We fully expect our contribution to have significant impact on the decisions and recommendations made by the committee's appointed working group.

You can help to ensure that newborn screening for ALD is mandated. Contact your state legislator by looking up their contact information at www.congress.org and let them know early intervention saves lives and saves money in terms of the prevention of costly long-term care. Please take advantage of any personal, professional, or business relationships you might have with your state legislators.

The Stop ALD Foundation is in regular contact with Neo Gen Screening and reviews progress with the scientists assigned to completing the ALD test. In an effort to collect samples that will be utilized in validating and fine tuning the test, Neo Gen Screening would like to receive anonymous samples from newborns with or without ALD. This will help Neo Gen Screening test the accuracy of their new test in order to help others. It is important to note that test results collected during this test validation phase will be processed in a completely anonymous fashion. No names or identifying information will be utilized. If you elect to assist by providing a blood sample, you will be helping a new test come to market that will help to catch ALD at birth.

If you are interested in providing a sample for testing, please contact Dr. Rachel Salzman at The Stop ALD Foundation (phone: 561.665.0455, email: rachel@stopald.org)


New Tools to Help Families Desperately Seeking Accurate Information, Direction, and Answers

There are a number of changes that will be coming to the web site (www.stopald.org) by the end of this year. One change will be the inclusion of a detailed Frequently Asked Questions (FAQs) section. In this section we'll put the answers that we provide to the most commonly asked questions that we receive. Monthly, we receive and quickly respond to hundreds of emails from families, researchers, and patients all over the world. Many of them have the same questions. We have been compiling our responses and plan to post them to this new Frequently Asked Questions (FAQs) section of the web site.

Another change coming to the site is a section entitled I just received a diagnosis of ALD. What do I do? Many inquiries we receive are from families that have just received the absolutely horrifying and devastating news that a loved one has been diagnosed with ALD. They are scared, confused, and lack accurate, credible, and timely information on what they need to do immediately. ALD can move extremely quickly along its destructive path. Sometimes, when the diagnosis is received, it's an early diagnosis as a related older child has been diagnosed and now a younger child is found to have the disease as well, but is not yet symptomatic. More often then not, unfortunately, the diagnosis is received and the child is already affected. At this point, sometimes, an emergency intervention can save the child's lifeTime is of the essence. But for ALD patients and their families, there is a tremendous lack of accurate, up-to-date information in the medical community. Sometimes, it's too late and there is nothing that can be done to save the child. But, then again, sometimes there is a very short therapeutic window measured in days or weeks where parents must move extremely swiftly in order to even have a chance at saving that child's life.

In the I just received a diagnosis of ALD. What do I do? section of the web site, we'll include:

check list of detailed questions to ask medical professionals (along with a brief explanation as to the meaning and importance of the questions). We have found that most people don't know the critically important questions they need to start asking immediately to ensure they are getting the best possible advice and care.

Steps that must be taken immediately

Steps that should be taken when time permits (e.g., having other children and family members tested)

Common ALD-related terms as there is a whole new set of words parents and care givers will need to understand

 Plan to see this new information on The Stop ALD Foundation web site by the end of 2003.


Now We Need Your Help

The Stop ALD Foundation's work is time consuming and takes funding to keep driving it forward. Many of us volunteer our time as we have a deep and personal passion for saving ALD patient's lives since we have family members that have or had ALD. While we are a small Foundation, we carry a big, powerful, and highly leveraged research punch.  Researchers around the world continue to be impressed with our impact and how we move the ball forward in finding better and more effective therapies for ALD and AMN.

But, we can't do it without continued funding.

We ask you to make your financial contribution to The Stop ALD Foundation today, and to ask family members, friends, and co-workers to contribute as well. Unlike making contributions to very large charitable organizations (e.g., a breast cancer research foundation), donors can be assured that their funds will have a large impact and that they will be making a material difference in many children's lives.

Financial contributions should be sent to:

The Stop ALD Foundation
500 Jefferson Street, Suite 2000
Houston, Texas 77002-7371

For more information on how to make a donation online (including via credit card) and how your company may be able to double your donation with company matching funds, please click on Make aDonation on our web site www.stopald.org. You may also call 713.756.3232.

As always, please feel free to contact us at the number listed above at any time and let us know how we may be of assistance. More contact information is available by clicking on Contact Us at www.stopald.org.

Thank you for your continued support.