Spliceosomal Peptide P140 for Immunotherapy of SLE
Spliceosomal Peptide P140 for Immunotherapy of SLE
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can lead to progressive organ damage. Patients with SLE experience unpredictable bouts of disease flare and are normally treated with high doses of corticosteroids or immunosuppressants which can have side effects that include obesity, diabetes mellitus, high cholesterol, high blood pressure and increased susceptibility to infection. These drugs may also contribute to irreversible complications such as ovarian failure, or increased risk of bladder cancer. To avoid these side effects, researchers are now focusing on developing alternative treatments that target the disease and are less toxic.
One such substance is P140, a short chain of amino acids known as a peptide that acts on the immune cells involved in SLE. P140 is a type of compound that is entirely different from what has previously been used for the treatment of lupus. In an early phase II clinical trial on patients with SLE, researchers found that P140 was safe, well tolerated and improved the clinical status of patients with lupus. The study was published in the December issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home ).
Led by Sylviane Muller of the CNRS's Institut de Biologie Moléculaire et Cellulaire in Strasbourg, France, under the sponsorship of ImmuPharma France, the study involved 20 patients with SLE from two centers in Bulgaria. All participants received three injections of P140 two weeks apart, but one group received 200 micrograms each time, while the other received 1,000 micrograms.
The authors measured the effectiveness of P140 by measuring anti-ds DNA antibodies that specifically occur in SLE. They found that anti-ds DNA levels significantly decreased in the 200 microgram group, but remained virtually unchanged in the higher dose group. They also measured immunoglobulin levels, that normally increase in response to infection and are also seen in patients with SLE, and found that they slowly decreased in the lower dose group. More importantly, the study showed that scores on the SLE Disease Activity Index (SLEDAI) significantly decreased in the lower dose group compared to baseline.
P140 was shown to be safe in the study, with only mild adverse events reported in the higher dose group. Only one adverse event, a mild rash at the injection site that quickly went away, was related to the drug.
"These findings confirmed the results of a phase I study in healthy volunteers and were in accordance with the results of preclinical animal toxicology studies," the authors state, adding that other peptide-based therapies have also been successful in animal studies. A phase IIb clinical trial of P140 involving about 200 patients from Latin America and Europe is already underway.
The authors note that this drug is specific to lupus, affecting cells in the immune system of SLE patients but not patients with other related autoimmune diseases such as rheumatoid arthritis. It also does not lower resistance to infection in mice, as do the immunosuppressants normally used to treat lupus. The authors conclude that P140 is "a novel potential candidate for the specific treatment of SLE patients of virtually any origin."
Item is available via Wiley InterScience at http://www.interscience.wiley.com/journal/arthritis.
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can lead to progressive organ damage. Patients with SLE experience unpredictable bouts of disease flare and are normally treated with high doses of corticosteroids or immunosuppressants which can have side effects that include obesity, diabetes mellitus, high cholesterol, high blood pressure and increased susceptibility to infection. These drugs may also contribute to irreversible complications such as ovarian failure, or increased risk of bladder cancer. To avoid these side effects, researchers are now focusing on developing alternative treatments that target the disease and are less toxic.
One such substance is P140, a short chain of amino acids known as a peptide that acts on the immune cells involved in SLE. P140 is a type of compound that is entirely different from what has previously been used for the treatment of lupus. In an early phase II clinical trial on patients with SLE, researchers found that P140 was safe, well tolerated and improved the clinical status of patients with lupus. The study was published in the December issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home ).
Led by Sylviane Muller of the CNRS's Institut de Biologie Moléculaire et Cellulaire in Strasbourg, France, under the sponsorship of ImmuPharma France, the study involved 20 patients with SLE from two centers in Bulgaria. All participants received three injections of P140 two weeks apart, but one group received 200 micrograms each time, while the other received 1,000 micrograms.
The authors measured the effectiveness of P140 by measuring anti-ds DNA antibodies that specifically occur in SLE. They found that anti-ds DNA levels significantly decreased in the 200 microgram group, but remained virtually unchanged in the higher dose group. They also measured immunoglobulin levels, that normally increase in response to infection and are also seen in patients with SLE, and found that they slowly decreased in the lower dose group. More importantly, the study showed that scores on the SLE Disease Activity Index (SLEDAI) significantly decreased in the lower dose group compared to baseline.
P140 was shown to be safe in the study, with only mild adverse events reported in the higher dose group. Only one adverse event, a mild rash at the injection site that quickly went away, was related to the drug.
"These findings confirmed the results of a phase I study in healthy volunteers and were in accordance with the results of preclinical animal toxicology studies," the authors state, adding that other peptide-based therapies have also been successful in animal studies. A phase IIb clinical trial of P140 involving about 200 patients from Latin America and Europe is already underway.
The authors note that this drug is specific to lupus, affecting cells in the immune system of SLE patients but not patients with other related autoimmune diseases such as rheumatoid arthritis. It also does not lower resistance to infection in mice, as do the immunosuppressants normally used to treat lupus. The authors conclude that P140 is "a novel potential candidate for the specific treatment of SLE patients of virtually any origin."
Item is available via Wiley InterScience at http://www.interscience.wiley.com/journal/arthritis.
