$100,000 AMN Research Grant Awarded to Dr. Florian Eichler, Massachusetts General Hospital

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.

$100,000 ALD/AMN Research Grant. Application Due Sept 23, 2016

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.

Secretary of Health and Human Services accepts the recommendation to expand the Recommended Uniform Screening Panel to include X-ALD and MPS I

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).


RFA for $50,000 for AMN research

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 scharle@mail.med.upenn.edu, 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.

Governor Signs Righter Legislation for Newborn Screening

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 - Biotin European AMN trial ongoing with results expected summer 2016.

MD1003 Update

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.

Laboratory Abnormalities

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.

Penn Orphan Disease Center Announces First Grant Recipients from Million Dollar Bike Ride

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...

The awards:

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...


New therapies being investigated for treating ALD/AMN

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: jf.dhainaut@ela-fondation.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 kpv@stanford.edu
  • 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

$44,000 raised for ALD at May 2014 UPenn Rare Disease Bike Ride!

On Saturday, May 3, 2014, the weather was gorgeous and nearly 20 riders on "Team ALD" participated in the first annual University of Pennsylvania Million Dollar Bike Ride for Rare Diseases.

See the photo gallery here.

  • ~20 riders for Team ALD.
  • 540 total riders in the event.
  • Team ALD raised $22,000 for ALD research and the University of Pennsylvania doubled that (since we met our $20,000 goal) and a total of $44,000 will be directed toward ALD research!
  • Overall, the event raised $1.4 million for rare disease research at the University of Pennsylvania!

Can't wait for the 2nd time the ride occurs in 2015!  Check here for more info.

Great legislation proposed for ALD Newborn Screening in California!

(Sacramento) -- Doctor Richard Pan, Democratic Assemblymember from Sacramento, has authored legislation to add Adrenoleukodystrophy, or ALD, to the list of genetic disorders all California infants are screened for when they're born. Dr. Pan says Assembly Bill 1559 can save a lifetime of debilitating problems for a child by properly diagnosing and treating ALD before its symptoms appear. Dr. Pan says other states already screen for ALD and a federal advisory committee has recommended ALD be added to the newborn screening list in all states. Here's more in this Assembly Access video. http://www.asmdc.org/pan