Huntington’s Disease is a genetic disorder in which the symptoms appear in mid-life usually between the ages of 35 and 50. The onset is insidious with mental signs often appearing first followed by generalized physical deterioration. Treatment is supportive with no specific medication available to counteract the symptoms. Once diagnosed the patient faces a slow downhill course as all bodily functions are lost.
There is now a glimmer of hope that may offer some promise in treating this dreadful disease.
The cause of Huntington’s Disease is a deficiency of a molecule named GM1 ganglioside. There is a fine line with this molecule — too much is not good and a lack or deficiency can lead to conditions such as Huntington’s. Humans and animals alike have GM1 ganglioside in their systems, some in their nervous systems and some in other tissues of the body. Mother Nature has provided most individuals a checks and balances system which controls the amount of this substance, accomplished by an enzyme.
The easy answer to help control Huntington’s would be to find a way to produce GM1 ganglioside.
Dr. Larry Holler, a veterinarian and faculty member at South Dakota State University, has selectively bred a line of sheep that lack the enzyme which controls the production of GM1 ganglioside. These sheep have a condition called GM1 gangliosidosis which causes them to make far more of the molecule than is necessary to meet their needs. Dr. Hollar has been breeding this line of sheep for over 20 years after figuring out the genetics necessary to maintain this unusual trait. GlycoScience Research is the name Dr. Holler has given to his production facility.
Lambs born with this condition produce up to 40 times the amount of GM1 necessary to sustain life. It is a condition that is incompatible with life and affected animals ultimately die. This disease will affect one in every four lambs born to carrier parents. Carrier parents will produce one lamb that is affected, two that are carriers (they show no symptoms) and one lamb that is normal. A test has been developed to determine the genotype status of each individual animal as an aid in selecting breeding stock that will allow for flock expansion. And it is these lambs that may serve as the source for the product that may help control Huntington’s.
Affected lambs are slaughtered and their nervous system tissue is harvested and frozen. At this point in the research the use of the carcass is not approved for consumption but based on current information it should be considered edible.
The flock maintained by Dr. Holler has been in the USDA Export Monitored Scrapie Certification Program for many years and has operated as a closed, high health sheep flock for the past 20 years. He currently has a flock of 450 carrier ewes with an additional 50 normal ewes. The normal ewes are used as recipients for embryo transfers and for the production of additional carrier animals.
The search for this potentially beneficial material is not new. In the late 1980’s and early 1990’s a firm was working with cattle brains as a source of GM1 and found that the quantities which could be extracted from them were enough to be commercially viable. At about this time Mad Cow Disease came on the scene rendering further study on cattle of no value. Other workers doing research on mice found that they could reverse the symptoms of Huntington’s in the species using GM1. It was at this time Dr. Holler came to realize that his sheep might help Huntington’s patients.
For any drug to find its way onto the market to treat disease in humans it must undergo a rigorous series of trials by the Food and Drug Administration (FDA) before being approved for such use. Dr. Holler has been working with Dr. Steven Hersch, clinician and researcher at Harvard/Massachusetts General Hospital, to work this drug through the system and it has met with some success. In January 2015, the FDA approved sheep as an acceptable source of GM1 to progress towards an Investigative New Drug (IND) application which would lead to human clinical trials. As is so often the case the big hang up is funding. At this time, money available for research is very tight and the competition for available dollars is intense.
Another factor that has to be considered is the number of sheep with the condition that are actually available to supply GM1 in the quantities needed for a pharmaceutical company to set up a production line that would be economically viable. It is estimated that it would take one to two lambs to supply the quantity of drug necessary to supply the needs of one patient for one year. Given the number of patients with Huntington’s and other possibly treatable diseases such as Parkinson’s, the number of sheep required would be very large.
The word of this progress has not been lost on the sheep breeders. Many of them have made inquiries as to how to develop programs in their own flocks that would have the potential to add significant income to their operations. At this time, some 17 additional flocks have signed on to the program which amounts to about 5,000 additional ewes.
The further development of this exciting program should encourage all of those afflicted with Huntington’s and related neurological diseases that hope is on the way. It is the further hope of those who have worked so long in the development of these advances that their efforts will be rewarded in a very real way.
For more information about GlycoScience Research and Dr. Holler’s work, visit www.glycoscienceresearch.com.