The good shepherds: Glycoscience Research Inc. advocates for cure for Huntington’s disease
December 16, 2016
This season, as we recall certain shepherds being delivered news of hope and joy, a group of modern day sheep owners and researchers are awaiting news that will also bring hope – particularly to those suffering from Huntington's, Parkinson's and Alzheimer's diseases.
The hope lies in a molecule called GM1 ganglioside. The wait is for clinical trials to use it on patients.
GM1 is naturally occurring in all mammals, but is found in high prevalence in sheep afflicted with a condition known as GM1 gangliosidosis. GM1 from bovine has been shown in clinical trials to slow and even reverse the debilitating neurological collapse of victims of Huntington's disease, referred to by those unfortunate enough to be familiar with it as simply "HD."
"Basic research has shown that if you take a culture dish of nerve cells and feed them GM1 ganglioside, they start growing new axons, which are the cell processes that make nerves function," says Dr. Larry Holler, founder and owner of Glycoscience Research Inc. of White, S.D. "We have always thought that couldn't be done – to regrow nerves."
For the past 20 years, Holler and his wife and business partner, Sue, have been working to bring GM1 into clinical trials to treat these neurological diseases. The procedure has been long, with the rigorous regulatory nature of the pharmaceutical industry all but halting progress at times.
In January, Holler and his team of collaborators – which includes Dr. Steven Hersch, a clinician and researcher at Harvard/Massachusetts General Hospital (Holler himself holds DVM and PhD degrees) – will submit a grant proposal to the National Institutes of Health that would fund safety and proof of concept studies necessary to lead to a clinical trial. This is the second time the corporation has submitted a grant to the NIH; the first was rejected.
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Holler says years of trying to get an industry focused on synthetic laboratory production of molecules to accept a product that comes from an animal source has been a struggle.
"Pharmaceutical companies are afraid of anything that requires animals to produce a drug," says Holler. "It's too complicated, too messy. But the reality is, there is no other way to produce GM1 ganglioside – if we could synthesize this in the laboratory, it would have already been done."
They hope to hear the status of their submission by March. If it's a go, clinical trials would be anticipated about three years down the road.
"We're cautiously optimistic that they would be willing to consider that these sheep will represent a cure for HD," says Holler.
The efficacy of GM1 ganglioside was well documented in the late '80s and early '90s, and it was one of the most prescribed treatments in Europe for neurological diseases. An Italian company partnered with U.S. researchers to study GM1 from cattle brains – until the break of European mad cow disease forced a halt. Holler notes that there is also research published in Canada that has shown GM1 ganglioside delivered directly to the brain can reverse signs of HD.
"The results have been nothing short of amazing," says Holler. "They can take mice that are on their way to dying and make them clinically normal again. The impact, at least in our animal studies, is pretty dramatic."
The molecule has previously been injected directly into brain tissue, but Holler says he thinks future application will likely be though something similar to a nasal spray.
The discovery of the high prevalence of GM1 ganglioside in the affected sheep was the result of studying the condition because it also occurs in humans. Sheep with GM1 gangliosidosis have concentrations of GM1 ganglioside at 30 to 40 times higher than normal animals – an incredible advantage over the original bovine samples.
While GM1 gangliocidosis is not a desirable trait – sheep suffer from musculoskeletal weakness and usually reach end stage of the disease by five months of age – it is recessive, and herds with the trait are carefully planned and contained. Because the lambs are harvested earlier and, due to the research tissue involved, carcasses are not allowed to enter the food chain. Producers who agree to select for the trait in their herds are paid a subsidy and the lambs are purchased by Glycoscience Research Inc.
Right now GRI has 13-14 cooperators that breed for the recessive genetics and are currently raising sheep for the research. Holler says that although the science field may think the sheep aspect is a burden, "from an animal production standpoint, these animals are worth a lot more for their chemical production than their lamb and wool. We believe it's a tremendous opportunity for value added sheep production in the U.S.," he says.
For the Hollers, and the families of those living with HD, the road to the cure can't come fast enough. The fact that it can come through something as organic and earth-derived as a lamb is more than coincidence.
"It's been a phenomenal journey," says Holler. "If I look back, I can see God's footprints throughout every step of this process.
"It's definitely not been an easy road. Probably not a day or a week goes by that my wife and I don't look at each other and wonder if we can keep on. But we think about the people and the friends we have met with HD – it's such an unrelenting disease; it just destroys these people – and we know we have to keep going."