The combination of enzyme replacement therapy (ERT) and Zavesca (miglustat) substrate reduction therapy (SRT) for a limited period improved disease symptoms in two women with Gaucher disease type 1 (GD1), according to a case study.
The study, “Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports,” was published in the Journal of Medical Case Reports.
Gaucher disease is one of the most common lipid storage diseases and is caused by mutations in the GBA gene. People with Gaucher do not produce enough glucocerebrosidase, an enzyme that breaks down a specific type of lipid molecules called glucocerebroside.
The result is the buildup of glucocerebroside in the liver, spleen, bone, and nervous system, ultimately affecting their function. GD1, which does not affect the nervous system, is the most prevalent type of the disease.
Presently, the disease is managed with either intravenous ERT or oral SRT, with some studies showing that SRT can be used as maintenance therapy after stabilization on ERT.
ERT, such as Cerezyme (imiglucerase), consists of the delivery of copies of the enzyme glucocerebrosidase to replace the deficient one, thus breaking down excess lipid molecules.
SRT, such as Zavesca (miglustat), partially blocks the production of the lipid itself, reducing its accumulation in the cells.
Although these treatments are usually used as monotherapies, some reports have described the use of combination therapy for a short period in Gaucher disease patients.
In this study, the cases of two female patients with GD1 who received combined ERT and Zavesca therapy to overcome unresolved clinical symptoms were reported by a team at Mount Sinai Hospital in Toronto, Canada.
The first patient was diagnosed at 17 and experienced worsening bone problems, even with Cerezyme treatment. Although a switch to Zavesca improved her bone symptoms, tremors led her to stop Zavesca and return to Cerezyme therapy.
Because her bone symptoms failed to improve, she began using a different ERT called VPRIV (velaglucerase). However, this treatment also did not lead to major improvements. The patient’s bone symptoms improved only when Zavesca was introduced in combination with VPRIV.
Gradually, the patient stopped ERT therapy, and her condition has been maintained successfully with Zavesca alone, with no recurrence of tremors.
“Thus, the miglustat [Zavesca] acted as a ‘booster’ to ERT in lessening bone pain in this patient,” the team wrote.
A second patient was diagnosed at the age of 3. She received Cerezyme for nine years, after which she switched to Zavesca while participating in a Zavesca clinical trial.
Although her core disease symptoms were maintained during Zavesca therapy, her disease parameters were slightly altered. She also experienced tremors and gastrointestinal problems.
Doctors decided to boost her Zavesca therapy with Cerezyme infusions, which successfully improved both disease symptoms and parameters. However, the combination therapy was terminated due to her relocation, and she remained on an increased dose of Cerezyme therapy.
“Overall, our two GD1 patients benefited from combination therapy, perhaps more in the case of patient 1 than in patient 2,” the team wrote.
Researchers concluded that although the majority of GD1 patients will not need combination therapy, “the current case reports demonstrate that judicious use of combination therapy may be of benefit in some cases.”