The shepherd’s gift: Devastating disease could be thwarted
ABERDEEN — When traveling through ag country, it’s not very common to see sheep grazing along country roads. In 1867, when inventory data began, the United States had about 45 million sheep and 38 million people. Today, the United States has about 5.2 million sheep and about 316 million people.
The Dakotas reflect that trend. The federal Agriculture Department says the South Dakota sheep and lamb inventory on Jan. 1 totaled 275,000 animals. In North Dakota, the sheep and lamb inventory totaled 74,000.
According to one producer, if research is approved, there could be a need for an additional 75,000 ewes each year to provide a potential treatment used to help patients suffering from Huntington’s disease (HD).
Dakota Lamb Growers Cooperative members heard from Larry and Sue Holler of White, S.D., on Saturday about why it is important to raise more sheep that carry the GM1 gangliosidosis trait. They hope these sheep can someday help those affected by HD. Coop members are considering an increase in production so that when clinical trials are started, lambs will be available to produce the material that holds promise for those with this devastating disease.
The Hollers said there are about 30,000 clinical HD patients in the U.S. with an additional 75,000 that carry the dominant genetic defect in the huntingtin protein gene. Using current estimates, one lamb could treat one HD patient for one year. The naturally occurring molecule, GM1 ganglioside, accumulates in the tissues of an affected lamb due to a single gene mutation in the enzyme that would normally break down the GM1 molecule. One fourth of the lambs produced in the GM1 flocks have the genetic condition GM1 gangliosidosis and produce elevated levels of GM1 ganglioside — reaching 40 times that of a normal lamb. Tissues are collected from affected lambs at slaughter, and the GM1 ganglioside is extracted in the laboratory.
At the present time, the GM1 can’t be synthesized, and GM1 sheep are the only verified source to economically produce GM1 ganglioside.
An FDA pre-investigative new drug meeting is anticipated in January. A Phase 1 clinical trial could be in place by late 2015, according to the Hollers. If the clinical trial outcome goes as expected, sheep producers will face the challenge of raising enough lambs fast enough to treat HD patients.
Researching the gene
While the term GM1 ganglioside is unfamiliar to most, it is critically important to a group of people who suffer from Huntington’s disease.
Families affected by HD formed a 501c3 non-profit called “The Shepherd’s Gift” to support development of GM1 for HD treatment. They hope to raise money to support sheep producers in their efforts to bring GM1 to the clinic.
During the last 20 years, the Hollers have built a flock of 400 genetically selected carriers for the GM1 gangliosidosis trait. The genetics have been shared with other producers in South Dakota, North Dakota, Iowa and Minnesota, adding 4,000 ewes to the project. The Hollers have worked with researchers to get the GM1 material into clinical trials for Huntington’s disease in conjunction with Dr. Steve Hersch, a clinical doctor and researcher from Harvard Massachusetts General Hospital.
Holler estimates that it could cost a couple of million dollars to get the substance to clinical trials. Dr. Hersch is concentrating on the funding and the trials while the Hollers are focused on raising sheep. They anticipate the FDA will be closely monitoring the progress.
The researchers hope the upcoming review by the FDA will be favorable, and they can quickly prepare for the clinical trial.
“It will be challenging to produce enough lambs to meet the need fast enough for those suffering with HD. That’s why it’s so important for us that these producers have taken the first steps to start growing the flock that will be needed in the future,” Holler said. “Through selective breeding, we’ve introduced a lot of different genetics, creating carrier sheep that should work in anyone’s flock.”
Carrier ewes are clinically normal and are raised in normal sheep production systems. At birth, affected lambs act normally and show no clinical differences from normal flock-mates. However, the affected lambs will eventually succumb to the gradual accumulation of GM1 ganglioside. They are slaughtered, and the needed tissues are collected and stored at 5 to 6 months of age. A genetic test is used at birth to identify affected, carrier and normal lambs.
Raise more sheep
Producers in the room were excited about the prospect about raising more animals.
Jeff Petersen has purchased nine of the carrier rams for his operation near Oakes, N.D.
“I think it’s a unique opportunity to help provide profitability,” Petersen said. “And the project has a great human aspect to help a community of people seeking to find a cure for their disease. It will be great if by raising lambs we can extend and improve the quality of their lives.”
Petersen believes this program will spur growth in the sheep industry. If the program works as expected, producers could receive $500 for a 60-day affected lamb. The current price for lambs is $1.50 to $1.60 per pound for a 140 lb. market lamb, resulting in a price of $210 to $224 per animal.
He believes this will encourage people to expand their flocks. It fits well with smaller to mid-size farms looking for an avenue to increase value on their operation. The investment required for sheep is lower compared to cattle.
At one time, there were a lot of sheep raised in the area. Petersen would like to see that return. Those who raise sheep do have some challenges, such as predators and fencing for animals. “A lot of buildings could be used for sheep production, including hoop buildings, old dairy barns, machine sheds could be retrofitted for animals,” Petersen said.
He said sheep adapt well, and there is a lot of crop residue that could be utilized for feed. He also pointed out that feed is readily available from the ethanol plants and sugar beet plants.
There was some sheep swapping taking place Saturday as the Hollers delivered two rams to Pete Kronberg from Forbes, N.D. Pete and his brother Thomas work with their dad Keith, raising 860 sheep. The family has raised sheep for a long-time.
“You have to have a different mindset to raise sheep,” Pete said. “We plan to expand next year, so it’s good to get the genetics started in our flock. If we can increase our lambing percentage to 200 percent, raising sheep could be very profitable, potentially more profitable than $7.50 a bushel corn.”
The undertaking will require further expansion of the GM1 flock as well as development of a producer network that can contribute production of affected and carrier animals into an integrated animal production system.
The Hollers said there are facilities to process all lambs currently produced; however, it is anticipated that a dedicated facility will be required to collect tissues from the large numbers of animals that would be needed for pharmaceutical production.
“This project is about value-added sheep production and the chance to help those who suffer with an untreatable disease. We believe these special lambs were created for this very purpose,” Holler said. “Raising affective lambs is not really any different than raising other lambs.” Holler estimates they will need 75,000 carrier ewes in the network to eventually produce enough GM1 for Huntington’s disease patients. Then there is Parkinson’s disease (PD). GM1 has already been shown to put Parkinson’s disease into a remission state in human clinical trials, and with over 1 million Parkinson’s patients, the demand for GM1 sheep could be significant.
“We are livestock producers, that’s where we stand,” Holler said. “Raising affective lambs is not really any different than raising other lambs.” Holler said. “Post mortem, the animals are the healthiest lambs we’ve raised. We estimate we will need 75,000 to produce for Huntington’s. There is the possibility that the substance could be used for Parkinson’s disease as well.”
“The technology is in place. The safety of GM1 has been established. The only thing holding up the process of bringing GM1 to the HD community is money,” Holler said. “We hope to send out every carrier ram that we can raise into the system. We can’t do it fast enough for those affected by Huntington’s disease.”
Larry Holler has a D.V.M. degree from Kansas State University and a Ph.D. from Washington State University. Sue Holler has a B.S. in Animal Science and a M.S. in Reproductive Physiology from Purdue University. For more information visit www.glycoscienceresearch.com.
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