In a potentially groundbreaking development, Canadian doctors have successfully used stem cell transplants for the first time to treat two cases of stiff person syndrome, a rare neurological condition in which a patient’s muscles suddenly and painfully contract, often leaving them immobilized or walking with a “tin soldier” gait.
The procedure, which was pioneered by Dr. Harry Atkins, a bone-marrow transplant specialist at the Ottawa Hospital Research Institute, led to the full clinical remission of two female patients suffering from the debilitating disease. ‘To our knowledge, this is the first report documenting that [stem cell transplantation] can produce long-lasting and complete remission of stiff person syndrome,” the researchers report.
Stiff person syndrome (SPS), which is also referred to as Moersch-Woltman syndrome, is a disease characterized by stiffness of the skeletal muscles, painful muscle spasms and, in severe cases, restricted mobility and/or inability to walk. The disorder, which affects an estimated one in a million people, is thought to occurs when the immune system turns against a person’s own tissues, in this case attacking cells in the brain and spinal cord.
However, the exact cause of SPS remains unknown. Doctors believe it has something to do with a deficiency of glutamic acid decarboxylase, or GAD. GAD is involved in the body’s production of gamma-aminobutyric acid, which helps control muscle movement. In patients with SPS, antibodies mistakenly attack certain neurons that produce GAD, leaving the body without the protein it needs.
The symptoms of SPS generally start to appear in patients after age 30. People with SPS initially experience muscle stiffness or discomfort. As the disease progresses, muscle spasms and rigidity become more pronounced. These muscle spasms can last anywhere from a few minutes to several hours, and are triggered by unexpected noises, physical contact, stress and/or emotional anxiety.
“Sometimes this happens when they’re startled,” said Dr. Atkins, who headed a team that transplanted stem cells into two women with the disease. “So you can imagine walking across the street and someone honks the horn and you can’t move, or you start falling and because your muscles can’t move, you just fall and you hurt yourself.”
“It really does provide a barrier with just going on with your life,” added Dr. Atkins.
Autologous hematopoietic stem cell transplantation (auto-HSCT) has been used to successfully treat patients with autoimmune diseases such as multiple sclerosis and scleroderma, which are resistant to more conventional treatment. A regimen of high-dose chemotherapy and antilymphocyte antibodies rid the body of diseased immune cells (immunoablation) before the immune system is regenerated with auto-HSCs. However, this is the first time the procedure has been employed to alleviate the symptoms of SPS.
Full remission achieved with novel stem cell transplant
Dr. Atkins, who was working on stem-cell transplants as a treatment for other auto-immune disorders, knew nothing about stiff person syndrome when a patient with the disease contacted him, begging him to perform a stem-cell transplant on her. After careful research, he agreed.
Dr. Atkins said he was particularly struck by one of the patient’s comments: That many people with the disease commit suicide because it is so horrible to live with. “That really stuck with me,” he said, “their lives are really affected in ways you can’t imagine.”
On Monday, Atkins and his team from the Ottawa Hospital Blood and Marrow Transplant Program published case studies of the first two transplants, both of which involved immunoablation and auto-HSCT, in the prominent journal JAMA Neurology. The results — both cases are now in remission — are being called a breakthrough and are garnering Atkins and his team attention from people outside Canada seeking treatment.
One of the women was diagnosed in 2005 at age 48 after having progressive leg stiffness, spasms, falls and walking with a “tin soldier” gait. The auto-HSC was performed in 2009. One month after the transplant, her SPS symptoms were resolved and she was fully mobile six months after the transplant and returned to work and playing sports. She remains asymptomatic nearly five years after transplantation.
The second woman was an otherwise healthy woman who had had periodic leg muscle stiffness that lasted several hours and she was eventually diagnosed with SPS in 2008 at age 30 years. She had stopped working and driving, and moved back in with her parents before undergoing auto-HSCT in 2011. Her post-transplant course was complicated by four periods of severe muscle spasms within 18 months of transplantation. The woman has been able to return to work and her previous activities. She has not had SPS symptoms in more than a year.
“I think for the period we’ve commented on for both patients, they’ve done very, very well,” said Dr. Atkins. “And it’s nice to see them back enjoying life.”
Conventional treatment for SPS involves a number of medications, including anti-anxiety drugs, muscle relaxants, anticonvulsants and pain relievers. Intravenous immunoglobulin can also reduce muscle stiffness and lower sensitivity to noise and other triggers. While such treatments can ease symptoms, they don’t cure the disorder, and not all patients get relief from the drugs.
Still, Dr. Atkins stressed that not every patient with SPS would be considered for a stem-cell, or bone-marrow, transplant, which requires that the person’s immune system be destroyed with high-dose chemotherapy before their previously removed and purified stem cells are reintroduced to create a new, disease-free immune system.
“It should only be considered where nothing more conventional is working … the symptoms have to be severe and the impact on their life very, very profound because there are risks associated with this,” he said, adding: “It is not a cure. We don’t know how long these remissions will last; it is just a few patients with a short follow. And there are risks associated with this procedure, it is not like taking a pill.”