GlycoScience Research Inc. 

Executive Summary of  ovine GM1 ganglioside Project

The proposed project is based on the need to develop a safe, plentiful, source of GM1 ganglioside for therapeutic use for clinical trials in Huntington’s disease, Parkinson’s disease, spinal cord injury and stroke.  The literature contains numerous recent publications on the potential applications of GM1 ganglioside.  The missing link is a safe, plentiful and sustainable natural source for ganglioside production.  Prior developments in the GM1 ganglioside field were pioneered by Fidia Pharma Spa in the late 80’s and early 90’s.  Their technology was based on GM1 production from bovine brain collected at slaughter plants throughout Europe.  Fidia had developed the GM1 ganglioside platform for many potential applications and had phase II clinical trials in progress for spinal cord injury and Parkinson’s disease when bovine spongiform encephalopathy (BSE, Mad cow disease) was diagnosed in cattle in England.  With the discovery of BSE, raw material from non-source verified animals of any species could not be reliably used for ganglioside production for pharmaceutical use.  With the Fidia technology, normal bovine brain ganglioside yields are approximately 230 mgs of GM1 ganglioside and 1400 mgs of mixed ganglioside per Kg of tissue.  GlycoScience Research has developed a new, verified, ovine (sheep) source for GM1 ganglioside production that will exceed these levels 30 to 40 fold, and provide needed raw materials for pharmaceutical applications.

Ganglioside Production from Ovine GM1 gangliosidosis sheep

GlycoScience Research (GSR) has developed a flock of sheep that are carriers for GM1 gangliosidosis.  Ovine GM1 gangliosidosis is an autosomal recessive, lysosomal storage disease in sheep associated with a profound deficiency of the lysosomal enzyme acid beta-galactosidase.  The stored products include GM1 ganglioside, asialo GM1 ganglioside and galactose-containing glycoproteins and long chain galactose containing oligosaccharides.  Affected animals contain markedly elevated levels of GM1 ganglioside and asialo GM1 ganglioside in the brain, spinal cord, and lesser amounts in other tissues in the body.  Since this disease is an autosomal recessive in inheritance, 1 out of every 4 lambs from carrier x carrier mating will be born with this disease.

The GSR flock is certified in the USDA Export Monitored Scrapie Certification Program and has operated as a closed, high health sheep flock for the past 20 years.  A molecular genetic test has been developed to determine genotype status of each individual animal and aid in the selection of carrier animals for flock expansion.  Tissues for ganglioside production are collected at slaughter at approximately 4 to 5 months of age and stored at -20°F until processed.  Currently, the carcass is not allowed to enter the commercial food chain; however, significant levels of GM1 ganglioside have not been detected in muscle tissue.  There is no reason to believe that with the demonstration of normal food safety and wholesomeness standards, the meat product from these lambs will not be allowed into normal marketing channels.  GSR has facilities to process all lambs currently produced, however, it is anticipated that a dedicated facility will be required to collect tissues from a large numbers of animals, as would be needed for pharmaceutical production.  Ovine GM1 ganglioside is currently produced from brain tissue supplied by GSR to Avanti Polar Lipids in Alabaster, Alabama.  Ovine GM1 ganglioside is currently produced for research use only.  Levels of GM1 ganglioside from brain are approximately 1.5 – 2.0 grams per brain.  Levels in spinal cord and other tissues such as salivary gland, adrenal gland, liver, kidney spleen, intestinal mucosa and many others are significantly elevated and maximum yield per lambs is expected to approach 4 to 5 grams based on preliminary data.  A more thorough analysis of all tissues will need to be performed.  Optimal extraction procedures, purification methods, maximum yields and production efficiencies will have to be optimized for large-scale production.  Avanti Polar Lipids has the capacity to develop necessary protocols for GMP manufacturing of ovine GM1 or provide necessary expertise if production was performed by a newly created entity.  Additional GM1 ganglioside can be recovered by conversion of polysialogangliosides or asialo GM1 to GM1 ganglioside depending on costs of production.  The overall goal will be to maximize the production of GM1 ganglioside from each affected lamb at a production cost that will maximize the affordability of a finished product.

GSR currently has a flock of 450 carrier females and approximately 50 normal females that are certified in the USDA Export Monitored Scrapie Certification Program.  We would continue to select primarily for carrier females, but maintain normal animals for use as recipients for embryo transfer procedures and production of additional carrier animals.  A number of carrier rams from a variety of genetic backgrounds are available to breed the GSR flock and to be used in the establishment of new flocks.  It is the vision of GSR to maintain a flock of carrier animals and provide the ovine GM1 gangliosidosis genetics to cooperator sheep flocks that would be willing to produce animals for pharmaceutical use.  Facilities are currently available to house the existing flock; however, additional facilities are in development for future expansion.  This flock is managed as a high health, sustainable commercial sheep flock.  Extensive development has taken place over the past 20 years and currently, procedures for production of GM1 gangliosidosis lambs for pharmaceutical production are in place.

Future Directions

GSR’s current emphasis is utilizing GM1 for the treatment of Huntington’s Disease (HD). Through collaboration with Dr. Steven Hersch, Harvard/Massachusetts General Hospital, ovine GM1 has been shown to decrease the mutant (disease-causing) huntingtin protein by 50%. In order to facilitate research progress, GSR is working on identifying partners to bring ovine GM1 ganglioside to the market as soon as possible.  The undertaking will require further expansion of the GM1 genetics. Currently, seventeen cooperator flocks, incorporating an additional 5000 ewes, have signed agreements with GSR to contribute production of affected and carrier animals into an integrated animal production system, while additional sheep producers are eager to join.  Tissue collection and processing will eventually be conducted in a facility similar to a modern abattoir.  We anticipate that meat and pelts from this project will be eventually marketed through normal channels once the safety concerns of the USDA are addressed.  Ganglioside production must be optimized to achieve maximum yields per affected lamb in order to be able to provide adequate product for the intended markets.  While other groups have suggested that synthetic ganglioside would be a more palatable alternative to a natural product, the reality is that the technology, although developed over a decade ago, cannot produce the significant quantities of GM1 ganglioside that will be required for pharmaceutical use.  It is the belief of GSR that unverified raw materials from any species will not be acceptable by the FDA for pharmaceutical production.  Currently raw material from ovine GM1 affected lambs is available to produce adequate material to conduct preliminary research and subsequently start a clinical trial for Huntington’s disease.

GlycoScience Research was incorporated in 1998 in White, SD.  This family-owned corporation was formed to develop a new sheep source for production of GM1 ganglioside for use in pharmaceutical applications including Parkinson’s disease and spinal cord injury.  The management team of GSR currently consists of its founders, Larry and Sue Holler.  Larry has a DVM degree from Kansas State University and a Ph.D. from Washington State University.  He is currently employed as a diagnostic pathologist and animal reproductive disease specialist in the Veterinary and Biomedical Sciences Department at South Dakota State University.  Sue Holler has a B.S. in Animal Science and an M.S. in Reproductive Physiology from Purdue University.  She has been employed in research, teaching and diagnostic positions at University of Idaho, Washington State University, and South Dakota State University respectively.  Together Larry and Sue manage the farm and research flock.

The rest of the hoof trimming crew:  Sue, Andrew, and Paul

Dr. Larry Holler, DVM, PhD, Pres. GSR trimming hooves



19 Responses to Summary



    • admin says:

      Liga 20 is not that difficult to make from GM1 but you do loose a little yield. For Parkinsons, it would be a very useful molecule. Suprising, it doesn’t work for Huntington’s as only GM1 appears to be effective. You cant make Liga 20, you need to start with GM1. The sheep have a genetic condition, GM1 gangliosidosis, that results in 40x accumulation of GM1 over normal animals. The abundance of GM1 would make it a great place to start production of derivitives like Liga 20. We have tried to work with a group on Parkinson’s befor, but we parted ways when it became clear that they were more interested in owning us so they could sell us, then getting GM1 approved for use. We are still trying to develop our source for GM1 ganglioside production, but its difficult getting the attention of pharma or VC for that matter. People are afraid of anything produced from a natural source. We have developed these animals in a closed, control system for over 20 years. Every animal is tracked from birth to death. The FDA is apparently convinced that our program is adequate. Hopefully we will find a way to use these special animals to help people. Thanks for the question. Larry

  2. Jamie Rutland says:

    Hello guys my name is Jamie, im 25 and i live in england. UK. Ive just came across your website and i am very intreged to know what GM1 can offer for Huntingtons? My dad has recently been diagnosed with the disease and is in the early stages. I also have 2 children of my own and i am absolutely devestated. I am also going to find out if i have the gene for my wife and childrens sake. I should know in about a years time. Please get back to me as i would do anything to try and save my family. Thankyou x

    • admin says:

      GM1 ganglioside was developed many years ago as a treatment for several neurologic diseases including Parkinsons and Spinal cord injury. The Sipione group in Canada recently reported GM1 ganglioside reverses clinical disease in several mouse models of HD. The problem that I have being trying to convince the Sipione group and the HD community in general is that while the early work in GM1 ganglioside was done with chemical purified from unknown soure cow brain, the advent of Mad Cow disease made this source and any like it unusable. We are trying to develop our sheep source for this purpose for several reasons. First, because of the genetics of our animals, affected lambs have 40x normal levels of GM1. Secondly, every animal has a record from birth to death. No new animals are added to the flock and the animals are certified in the USDA export monitored scrapie certification program. We currently sell the ovine GM1 for research use through Avanti Polar lipids, but we hope to be able to scale up to treat HD patients. Unfortunately, we are having a difficult time getting anyone to talk with us. But we will not give up. We have made great progress with the sheep source and are ready to expand to meet a pharmaceutical market. We have completed preliminary animal studies with our GM1 with a researcher at Mass General in Boston and a short two week treatment was enough to reverse the mutant Huntingtin protein levels to normal. We hopefully will find someone to help navigate the FDA and complete the work necessary to put GM1 on the market.
      It is for you that we keep going.
      Larry Holler DVM, Phd

  3. Dr.Dhanushkodi says:

    Dear Dr.Larry Holler,
    I am from India. I am basic science researcher working on neuroprotection in temporal lobe epilepsy and Parkinson’s disease. We recently published our preliminary findings about the neuroprotective action of GM1 against kainic acid induced neurodegeneration. We infused V. cholerae sialidase into lateral ventricles to enhance the endogenous GM1 level for neuroprotection. For my future research I would like to make it more clinically relevant and want to try GM1 analogue like LIGA-20. However, I am finding it difficult to identify the sources from which I can obtain LIGA-20. I seek your advice in this regards and kindly request you to direct me to a source where I can get this drugs.
    Please consider this as a personal communication.
    With best regards,

    • admin says:

      Dear Dr. Dhanushkodi,
      I am not aware of any Liga 20 that is commercially available. The Liga 20 that is in the literature is left over from Fidia Pharma back when they where still in business. The manufacuted their Liga 20 and many other derivitives starting from GM1 ganglioside. Our GM1 is available for research use and we are hoping to get approval from the FDA for a clinical trial in Huntington’s as soon as possible. Our GM1 is currently marketed through Avanti Polar Lipid in Alabama. They might be able to help produce some Liga 20 for you if you are interested. Their contact number is 205- 663-2494 for international sales. If I can be of any assistance, you can contact me also at, 605-688-5798.
      Take care,
      Larry Holler DVM, PhD

  4. Beverly Rogers says:

    Dear Dr Holler
    My name is Beverly I belong to a JHD an HD Group on Yahoo an one of the ladies came
    On there an wrote us all a long very Impressive Email About you And your wife’s
    research . My stepson Jason Died Nov 2011 of
    Pneumonia He aspirated His lungs field and they couldn’t really do anything for him
    He made his dad promise to let him go. He was Diagnosed at 22
    And dead at 30. No one in our family has this not on moms side or dad side If they did it was never diagnosed.
    He has a brother an a sister Same parents I watched him go From a Vibrant man nothing. It’s too late for him But I use so many research doctors in Memphis Tennessee St. Louis Texas I will send all that I can to all of them if u let me know what to send them I’m just a county girl from the hills of Arkansas but trust me those Doctors know when I’m coming. Tk you for all your hard work an we will push this untill they get Tired of hearing us .

    Have not been tested

    • admin says:

      Dear Beverly,
      Thanks for the post. The first place to start with the medical community is to send them a link to the PNAS paper by Simonetta Sipione from the University of Alberta, detailing the animal studies with GM1 for HD. We have link to the article back in the reference section. Hopefully this information will convince them to investigate further. They can learn about our project on this website or they could contact me directly.
      Take care and thanks for your interest,
      Larry Holler DVM, PhD

  5. Tara Hansen says:

    GM1 for JHD 🙂

  6. Linda Gisvold says:

    we sure need your help, my 14 yr. old granddaughter has jhd, she has been on several meds, ” no help,some make it worst.”She needs all the help we can find. This sounds like a good thing, please get us in your prayers and in your search to help find a cure.

    • admin says:

      We will keep your granddaughter in our thoughts and prayers. These lambs are a special creation of God, and we believe that his purpose for them will soon be revealed.
      Take care,

  7. DR HOLLER says:

    DR HOLLER is there any where in the world i can take my wife for gm1 treatment for parkinson’s
    36 ADMIRAL DR.
    440 946 9236

    • admin says:

      My heart goes out to you and your wife. There is no GM1 available that I am aware of. We are working as hard as we can to get our GM1 approved for HD and PD. We have made quite a bit of progress, but the task sometimes seems overwhelming. But we will not give up until we have completed the task.
      Feel free to call me if I can be of any help.
      Take care,
      Larry Holler
      605 605-0984

  8. Mary says:

    My brother shared your website with me as his wife has HD and we are very interested in your research. I’ve been managing Clinical Research Studies for about 20 years in both Pharma and Device industry. I would like to find out more about your research and potential clinical trial. My email is and I can also be reached at 262-825-8304.
    Kind Regards,

    • admin says:

      Thanks for your interest in our project. I will send you an email in addition to this response. I enjoy visiting with your brother and I share his need for urgency.
      Take care,
      Larry Holler

  9. Tricia Wempe says:

    Go Larry and Sue!

    I am so amazed at your perseverance and hard work! 20 plus years with GM1 work is a long time.

    May God speed your success with the HD population! We are a desperate community that needs drug intervention yesterday!

    Hang in there!

    Warm Regards, –Tricia Wempe

    • admin says:

      We pray that these lambs can bring great relief to the HD community. It’s be a long road, but God has been faithful in sustaining us over the years.
      Keep praying,

  10. Ali Choucry says:

    I am a researcher in Pharmacology and Toxicology, and have been interested in the possible benefit of gangliosides and their derivatives in ischemic stroke. However I have been looking everywhere for the LIGA20 without success. Do you have any idea where can I obtain it? Thanks in advance!

    • admin says:

      To my knowledge, no one is currently making LIGA20 since Fidia quit making it year ago. If I am correct, I believe you start with the parent GM1 and modify accordingly. We might be able to make some for you from the sheep GM1 through Avanti Polar Lipids.
      Larry Holler DVM, PhD

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