Research from a new study has shown that an autologous non-myeloablative hematopoietic stem cell transplantation in patients with stiff person spectrum disorder might be safe and effective.
Stiff person syndrome or stiff person spastic disorder (SPSD) is a progressive autoimmune neurological disorder characterized by painful and debilitating episodic muscle spasms and stiffness.
In most cases, people with SPSD have antibodies to glutamic acid decarboxylase (GAD), an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA). GABA is a key neurotransmitter needed for the control of muscle movement.
The standard therapeutic approach is the use of GABA agonists, such as baclofen and benzodiazepines, and physical therapy. However, a one-time treatment that could reduce or eliminate the need for treatment with drugs that have the risk of dependence would be a beneficial medical contribution for the management of SPSD. To this end, a clinical trial to study the therapeutic efficacy and safety of nonmyeloablative autologous hematopoietic stem cell transplantation for SPSD was conducted at Northwestern University, Chicago, Illinois.
The researchers conducted a prospective open-label cohort study with 23 patients with SPSD who were between the ages of 18 and 60, had antibodies to GAD, and who exhibited muscle stiffness and painful spasms. The patients were initially treated with cyclophosphamide and filgrastim (for granulocyte production) for hematopoietic stem cell mobilization. They were then hospitalized two weeks later for the immunosuppressant conditioning phase and the hematopoietic stem cell treatment phase.
Patients received a one-time infusion of their hematopoietic stem cells, and various assessments were made throughout the course of the hospitalization. Safety was assessed by survival and according to the National Cancer Institute adverse event criteria. The main outcome measures were reduction or discontinuation of antispasmodic drugs and quality of life.
Seventy-four percent of participants responded, and 47% remained in remission for an average of 3.5 years. However, the response was highly variable in that responders tended to be those who had pre-transplantation intermittent muscle spasms, positive CSF anti-glutamic acid decarboxylase serology, did not have lead pipe rigidity, and who were not taking SSRIs or SNRIs. Although the results are intriguing, more studies are needed to determine an approach that is effective to a broader patient population and cost-effective.
Lyles, A. (2021). Hematopoietic Stem Cell Transplantation Found Safe and Effective for Patients with Stiff Person Spectrum Disorder. Neurology Today, 21(2), 21-22. doi: 10.1097/01.nt.0000733400.95524.1a