Katharina Schwan, who studies genetic counseling at California State University in the San Francisco/Bay Area, is conducting a research study on families who have received a positive ALD newborn screening result. Participants receive $25 compensation for their time. Please click here for more information.
The Stop ALD Foundation is excited to announce that the University of Pennsylvania's Orphan Disease Center has awarded a $100,000 research pilot grant to Dr. Ali Fatemi at The Kennedy Krieger Institute.
A significant hurdle for translating preclinical work into clinical trials for Adrenomyeloneuropathy (AMN) is the slowly progressive nature of AMN with extremely variable rates of progression. There is a critical need for surrogate biomarkers which can predict disease progression, or identify individuals who are rapid progressors. Effort is needed to be “clinical trial ready” so that therapeutic treatments can be tested for efficacy.
This grant will fund assessment of existing Kennedy Krieger longitudinal magnetic transfer (MT) and diffuse tensor imaging (DTI) magnetic resonance imaging (MRI) of the brain and cervical spinal cord of AMN patients to look for significant changes over a 12-month period. In addition, standardized neuroimaging protocols will be implemented which can be executed at 4 main ALD Connect clinical trial centers. The identification and implementation of a multicenter imaging protocol for AMN is needed to allow the full implementation of the ALD Connect multicenter clinical trial network.
This work will serve as an important foundation for the broad research community, supporting a range of therapeutic approaches being studied by many dedicated researchers.
This $100,000 grant was a result of the University of Pennsylvania Orphan Disease Center's annual Million Dollar Bike Ride. The Million Dollar Bike Ride focuses on raising money for rare disease research doubling the amount of money raised by its participants. The Stop ALD Foundation lead the ALD team and raised a total of $50,000, of which The Stop ALD Foundation contributed $40,000, amplifying donor money into important research areas. Dr. Fatemi’s grant will advance much-needed research.
Grant Awarded: $100,000
Project Title: Multicenter Cross Standardization of Magnetic Resonance Imaging Methods for Adrenoleukodystrophy/Adrenomyeloneuropathy.
Project Goal: Implement, cross standardize and validate MRI protocols necessary for clinical trials in Adrenomyeloneuropathy (AMN), the adult form of X-linked Adrenoleukodystrophy (ALD), for the ALD Connect Consortium.
Brief Background: Adrenomyeloneuropathy (AMN) is the adult variant of X-linked ALD and is a slowly progressive neurodegenerative disorder due to mutations in the peroxisomal AcylCoA transporter, ABCD1, with no current therapeutic options. However, over the last 10 years, at least 5 different biotechnology companies have developed a research and development program for AMN and encouraging results are emerging from preclinical studies. Furthermore, several neuroimaging methods have been studied in AMN and could serve as biomarkers. Yet, the conduction of clinical trials is hampered by rarity of the disorder and lack of standardized quantitative outcome measures. In an effort to overcome these issues, ALD Connect, a new consortium, was established a few years ago with the goal to cross-harmonize data collection.
Importantly, MRI imaging protocols are not standardized between centers specialized in ALD for clinical trials, due to varying MRI scanner models and paradigms. In collaboration with Dr. Seth Smith, we have developed tools that will allow the harmonization of imaging protocols between the nation’s five main clinical sites.
- Aim 1: Develop a standardized imaging protocol and MRI sequence for AMN trials which is executable by all included site MRI scanners and infrastructure.
- Aim 2: Implement imaging protocols by performing on-location MRI brain scans of a single healthy control subject at each trial site. Assess equivalency of MRI scan data between sites at The Kennedy Krieger Institute, and implement necessary protocol changes at the trial sites. Establish a communication and review platform between AMN and imaging experts for the trial sites as a multi-center imaging network.
In a First, Gene Therapy Halts a Fatal Brain Disease
For the first time, doctors have used gene therapy to stave off a fatal degenerative brain disease, an achievement that some experts had thought impossible.
The key to making the therapy work? One of the medicine’s greatest villains: HIV.
The patients were children who had inherited a mutated gene causing a rare disorder, adrenoleukodystrophy, or ALD. Nerve cells in the brain die, and in a few short years, children lose the ability to walk or talk. More...
Parents Lobby States To Expand Newborn Screening Test For Rare Brain Disorder
Kerri De Nies received the news this spring from her son's pediatrician: Her chubby-cheeked toddler has a rare brain disorder.
She'd never heard of the disease — adrenoleukodystrophy, or ALD — but soon felt devastated and overwhelmed.
"I probably read everything you could possibly read online — every single website," De Nies says as she cradles her son, Gregory Mac Phee. "It's definitely hard to think about what could potentially happen. You think about the worst-case scenario." More...
The 2017 Million Dollar Bike Ride Pilot Grant Program is now open! The MDBR Pilot Grant Program provides a one-year grant to support research related to a rare disease represented in the 2017 Million Dollar Bike Ride. Thirty-three (33) total grant opportunities are listed below.
Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.
To Apply: Please review the RFA guidelines here. Interested applicants must first submit a Letter of Interest (LOI) which can be found here. This LOI is due by Monday, September 18, 2017 by 8pm EST. Full applications are accepted by invitation only after LOIs are approved.
Research Focus Areas for Pilot Grants:
1) Adrenoleukodystrophy (ALD): One $101,164 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Grants should focus on activities that lead towards a clinical trial. Adrenoleukodystrophy (ALD) is an X-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.
The Stop ALD Foundation is excited to announce that the University of Pennsylvania's Orphan Disease Center has awarded a one-year, $100,000 research pilot grant to Dr. Florian Eichler at Massachusetts General Hospital. Dr. Eichler and his team have already established an Adrenomyeloneuropathy (AMN) animal model proof of concept showing a gene therapy approach could provide benefit where no treatment is currently available. Today when young men with Adrenoleukodystrophy (ALD) begin showing adult-onset signs of AMN, they slowly lose their ability to walk. This pilot grant will help move Dr. Eichler's research program forward towards human studies. However, additional funds will still be necessary to initiate the study.
This $100,000 grant was a result of the Penn Orphan Disease Center's annual Million Dollar Bike Ride. The Million Dollar Bike ride focuses on raising money for rare disease research doubling money raised. The Stop ALD Foundation lead the ALD Team and raised a total of $50,000 of which The Stop ALD Foundation contributed $40,000, amplifying donor money into important research areas. Dr. Eichler's grant will advance much-needed research into a promising treatment for Adrenomyeloneuropathy (AMN). This $100,000 pilot grant is just the beginning and we encourage other donors and foundations to fund this important AMN research further to help it move towards a clinical trial.
2016 Million Dollar Bike Ride Grants
The 2016 Million Dollar Bike Ride Pilot Grant Program is now open! The MDBR Pilot Grant Program provides a one-year grant to support research related ALD/AMN.
Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.
To Apply: Please be sure to read the MDBR RFA Guidelines before applying. Submit your Letter of Interest (LOI) via the link below no later than Friday, September 23, 2016 by 8pm EST. Full application is by invitation only, after review of LOIs.
LOI Submission Form: LOI Submission Form Due 9/23/16 by 8pm EST.
Research Focus Areas for Pilot Grant:
Adrenoleukodystrophy (ALD): One $100,000 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Adrenoleukodystrophy (ALD) is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.
Cold and rainy and worth every minute of it! The Stop ALD Foundation participated in the annual Million Dollar Bike Ride at UPenn in Philly on May 7, 2016. We have until May 30, 2016 to accept donations. Our goal is $20k and at that goal our fundraising will be doubled to $40k. Click here to make a donation. Honored to ride today with Kyle Bryant of FARA!
The 3rd Annual Million Dollar Bike Ride for Rare Diseases is coming up May 7th in Philadelhphia. Please consider riding or making a donation where UPenn has a grant to DOUBLE all donations. Great chance to make a difference and have your contribution doubled! http://www.milliondollarbikeride.org/
Secretary of Health and Human Services Sylvia Mathews Burwell, accepted the recommendation to expand the Recommended Uniform Screening Panel (RUSP) to include the addition of X-linked Adrenoleukodystrophy (X-ALD) and Mucopolysaccharidosis type 1 (MPS I). The Affordable Care Act requires that most health plans cover evidence-based preventative care and screenings provided for in the comprehensive guidelines supported by Health Resources and Service Administration (HRSA).
The 2015 Million Dollar Bike Ride Pilot Grant Program is now open. Please first review the RFA guidelines before submitting your pre-application using the webform below. All pre-application submissions are due Monday, September 14, 2015 by 5:00 pm (EST). If your pre-application is approved, you will be notified with an invitation to submit a full-application, due October 19, 2015.
For questions regarding this pilot grant program, please contact Samantha Charleston at firstname.lastname@example.org, or (215) 573-6822.
Click here to view the 2015 MDBR Pilot Grant RFA Guidelines: 2015 MDBR Pilot Grant RFA Guidelines
Click here to submit your pre-application:
Research Focus Areas for Pilot Grants:
Adrenoleukodystrophy (ALD): Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, known as Adrenomyeloneuropathy (AMN) develops in young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved.
One $50,000 pilot grant is available with a focus on treatments for Adrenomyeloneuropathy (AMN), the adult form of the disease. We are interested in proposals that would provide a path towards a treatment, including advancing the understanding of what can be used as endpoints when conducting an AMN trial. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.
Legislation requiring the Illinois Department of Public Health to provide all newborns with screening tests for the presence of adrenoleukodystrophy (ALD) under a new law sponsored by State Sen. Dale Righter (R-Mattoon) was signed Wednesday by Gov. Bruce Rauner.
“Screening for ALD at such an early stage will help save lives,” Righter said. “All too often, those with ALD are diagnosed too late for treatment to work. It’s a terrible disease, but this law helps us get out in front of it and save our children.” More...
MD1003 is an experimental medicine that consists of extremely high doses of pharmaceutical-grade biotin. Whereas daily biotin requirements are in the range of 30 MICROgrams/day (mcg), this agent is dosed at 300 MILLIgrams/day (mg). There are 1,000 micrograms in ONE milligram.
ALD Connect Work Group 3 had a discussion with Dr. Frederic Sedel, the CEO of MedDay Pharmaceuticals in May 2015. MedDay is the French biotech that is developing MD1003 in both multiple sclerosis (MS) and adrenomyeloneuropathy (AMN). Biotin is also known as Vitamin H or Vitamin B7. Recently, the company reported positive data in Progressive MS, so we wanted to hear Dr. Sedel's advice for AMN patients who might be interested in taking alternative forms of MD1003 off label. There is a European AMN trial ongoing with results expected next summer (2016).
In spite of a promising outcome in MS, there are concerns unique to AMN that prevent a direct correlation between the two diseases. In fact, that is one reason the company is advancing the AMN clinical trial. Here are some specific issues that Dr. Sedel shared with The Stop ALD Foundation:
Possible Impact on AMN
Biotin is a co-factor for several enzymes involved in energy production and as such is believed to be beneficial for AMN patients. Biotin is also a cofactor of acetyl – CoA carboxylase. This carboxylase is involved in fatty acid synthesis and may play a role in myelin synthesis. Due to its role in fatty acid synthesis it is theoretically possible that MD1003 may impact (increase) VLCFA levels. Although the effects of VLCFA in ALD remain to be fully elucidated, there are a percentage of AMN patients who convert to cerebral onset, which is a more severe disease. Thus there may be a theoretical increased risk for deleterious effects in the background of increasingly elevated VLCFA’s. However, VLCFA increase has not been observed so far in preliminary studies in one patient treated by MD1003, nor in laboratory experiments using patients’ fibroblasts (skin cells).
Teratogenicity (Birth Defects)
It is still not clear if these very high doses of biotin might be associated with birth defects. Teratogenicity has been observed in one animal species at a dose close to the therapeutic dose used in humans. Given the gravity and seriousness of such a side effect, it is strongly recommended that women of childbearing age avoid this product. It is also not known if any effects might be transmitted through a man's reproductive organs.
Investigators learned from the Progressive MS trial that several patients on MD1003 experienced a series of abnormalities on blood tests. Although the lab work was indicative of a disease state in 4 patients (hyperthyroidism), it turned out that these were only artifacts because there is something about the high-dosed biotin that interferes with immunoassays. For example, a person on MD1003 may appear to have thyroid abnormalities to the point where a prescription is provided or even surgery is recommended. The challenge is how to distinguish some of these artifacts from real disease? The lab work would appear the same, regardless of whether the patient is sick or not, and not all diseases are accompanied by overt clinical symptoms. This confusion can be the case with dozens of lab tests in a person on high dose biotin. In contract to the previously mentioned potential for AMN exacerbation and teratogenicity concerns, this is a proven effect associated with the drug, and not just a theoretical or hypothetical happening. Of note, interferences are only observed with certain analysers using biotin as a reagent. The tests can be accurately performed after stopping the treatment with MD1003 for several days (at least one week).
Altered Lab Results Impacting Cortisone Pathways
Given the common incidence of adrenal insufficiency associated with ALD/AMN, and the ongoing and critical need for adrenal replacement, it is essential that patients have accurate ACTH and cortisol monitoring. These laboratory tests can be confounded in patients on MD1003, which could affect proper steroid dosing, and lead to adrenal crises.
Going forward MedDay is developing careful management and educational tools to address the issue of abnormal lab results, which can happen in an estimated 100 different tests.
Purity of Product and Intellectual Property
The product contained in MD1003 is pharmaceutical grade biotin. This is quite different than supplement-grade products, which do not have the same ongoing requirements of purity and potency. Supplement content can vary from batch to batch and also may contain impurities.
That being said, one can likely outsource pharmaceutical-grade manufacturing at an approved and certified facility and obtain pure biotin. As for any drug in development, it is not recommended that this be done outside the context of a clinical trial before the safety and efficacy data have been fully assessed.
We had a great Million Dollar Bike Ride for Rare Disease Resaerch this past Saturday in Philadelphia! Our team was one of 24 total for a variety of rare diseases. We raised over $20k which will be doubled by UPenn to $40k for researchers to apply for ALD research grants. Thanks for everyone's support!
The 2nd annual University of Pennsylvania Million Dollar Bike Ride (MDBR) for Rare Disease Research takes place May 9, 2015 in Philadelphia. For adrenoleukodystrophy (ALD) / adrenomyeloneuropathy (AMN), please help us hit our $50,000 goal by supporting us here.
It would be great if you could also join the ride. Sign up to ride here and select "Stop ALD" as the team you are riding for and "Registration without Fundraising"
The MDBR will match every dollar we raise so we can turn $50,000 into $100,000 for critical ALD/AMN rare disease research. Last year we raised $25,000 and that was doubled to $50,000. The University of Pennsylvania lead the section process awarding the $50,000 grant to a great ALD/AMN researcher at Mass General in Boston.
Please let us know if you have any questions and thanks in advance for your support!
Steve Barsh & Amber Salzman
The donation of Preimplantation Genetic Diagnosis (PGD) tested and affected embryos to stem cell research at the University of Michigan
For couples with a family history of inherited diseases like Leukodystrophies, that cause pain, suffering, and sometimes death, in vitro fertilization (IVF) treatment with Preimplantation Genetic Diagnosis (PGD) makes it possible to build a family without the risk of passing on the mutant gene and known disease to their children.
Inherent in PGD testing is the production of embryos which test positive for genetic defects. Typically, these disease-affected and abnormal embryos are deemed “not suitable for implantation” and are discarded. Couples now have the opportunity to make a valuable contribution to our understanding of the diseases, many times present in their families such as Adrenoleukodystrophy (ALD), Canavan Disease, Krabbe Disease, and Metachromatic Leukodystrophy, by donating these otherwise discarded embryos to embryonic stem cell research at the University of Michigan’s Stem Cell Program.
This University of Michigan program, called MStem Cell Laboratories, has already produced the world’s first ALD disease-specific human embryonic stem cell line†. Embryos carrying any single-gene disease for which PGD testing is available, (such as those listed above) may be donated to the University of Michigan Institutional Review Board (IRB) approved study.
Is it difficult to donate?
Not at all. Prior to beginning their IVF cycle, couples interested in donation of PGD-tested and disease affected embryos review and sign an informed consent document provided by the University of Michigan. During the consent review, our Study Coordinator will speak by phone with both the female and male interested in embryo donation to answer any questions they may have. Our Study Coordinator also works directly with each couple’s fertility healthcare provider to facilitate the embryo donation process.
Where can I learn more?
Visit the University of Michigan Stem Cell Program website at: www.stemcellresearch.umich.edu/donation/donors.html, or you can call our Study Coordinator at +1-734-649-6557, who will be glad to assist you.
* Nakano et al. Cell Stem Cell (2012) Vol: 10 Issue 6
Newswise — PHILADELPHIA — The Orphan Disease Center at the Perelman School of Medicine at the University of Pennsylvania, has awarded its inaugural grants funded by proceeds from the 2014 Million Dollar Bike Ride. Thirteen institutions – from academia in the US, Canada, Germany, and Australia – received grants ranging from $35,000 to $60,000 from funds raised by 13 disease-specific cycling teams...
Team ALD (Adrenoleukodystrophy)
Florian Eichler, MD
Massachusetts General Hospital / Harvard Medical School
Pilot study on adeno-associated virus serotype 9-mediated gene therapy for adrenomyeloneuropathy
Read the whole article here...
As a result of the Million Dollar Bike Ride, the Center for Orphan Disease Research and Therapy (CODRT), announces a Request for Applications (RFA) for a $50,000 a pilot grant for Adrenomyeloneuropathy (AMN).
The Timeline for the RFA / grant Program is as follows:
- August 4, 2014 -- RFA Release Posted.
- September 15, 2014 -- Pre-application deadline; documents are to be uploaded no later than 5 pm ET. Click here for Rare Disease Pilot Grant Pre-application.
- September 18, 2014 -- Invitation to submit a Full-application
- October 15, 2014 -- Full-application deadline (by invitation only). Documents are to be uploaded no later than 5 pm ET.
- December 1, 2014 -- Anticipated start date.
If you have any questions, please contact:
Linda Aversa-Caldwell, MS
Associate Director, Center for Orphan Disease Research and Therapy (CODRT)
University of Pennsylvania
An ALD Connect workgroup lead by Rachel Salzman, CSO The Stop ALD Foundation, and Kendrick Goss, Scientist II at bluebird bio provided an update at the ALD Connect/ULF meeting in Baltimore July 30 - August 3, 2014. A list of potential treatments were considered and narrowed down to the following:
- Ampyra, a K+ Channel blocker, is said to improve nerve conduction, however no published data exists for ALD/AMN. It is approved for MS.
- MD 1003, an anti-oxidant, is energy producing in neurons and repairs demyelination. Data on one AMN patient was reported and a multi-center AMN trial is being launched in Europe (not available in the US). Contact: email@example.com
- EPI-743, an anti-oxidant, shown to reduce oxidative stress in vitro. An AMN trial is close to being initiated in Italy. Contact: Keith Van Haren at firstname.lastname@example.org
- Natalizumab, an anti-integrin, is known to block lymphocyte infiltration in CNS. In-vitro data has been reported but not published. ALD experts have a strong interest in pursuing. It is approved for MS.
- AAV, an in vivo gene therapy treatment. In-vitro and in-vivo mouse data has been shown to lower VLCFAs. More work is ongoing to further prepare for a human study (not prior to 2016).
- Sobiterome, a thyroid agonist that up regulates ABCD2. In-vitro and in-vivo data has been reported but not published. A clinical study is under design.
Team members will continue to consider how to best move forward efforts.
Team members include:
- Joshua Bonkowsky, Univ of Utah
- Nancy Braverman, McGill
- Marie-Josee Duran, ELA
- Florian Eichler, Mass General
- Ali Fatemi, KKI
- John Fink, Univ of Michigan
- Kendrick Goss, bluebird bio
- Stephan Kemp, Univ of Amsterdam
- Troy Lund, Univ of Minnesota
- Sanjay Magavi, Vertex
- Alex McCampbell, Biogen Idec
- Patricia Musolino, Mass General
- Asif Paker, bluebird bio
- Rachel Salzman, The Stop ALD Foundation
- Keith Van Haren, Stanford.
- Inna Tzvang, ALD Connect