Isoprinosine

Isoprinosine is a multi-functional medication which has both antiviral and immuno-modulating properties. It is prescribed against a variety of chronic and acute viral infections such as herpes, influenza and viral hepatitis. It halts the process of neurological deterioration and can be extremely helpful to people with a progressive subacute sclerosing panencephalitis, a viral infection of the central nervous system. Also, it decreases the risk of infection in people who have undergone immune system suppression (e.g. chemotherapy). Isoprinosine fights the infections by mirroring the actions of immuno-stimulating hormones and strengthening the immune system. For these properties the medication is well known in cancer and HIV infection. Studies have shown that administration of Isoprinosine delays the onset of AIDS in HIV positive patients and is a very good complement to any anti-cancer therapy.

BJOG. 2007 Apr;114(4):509;
Oral inosiplex in the treatment of cervical condylomata acuminata: a randomised placebo-controlled trial.Georgala S, Katoulis AC, Befon A, Georgala C, Rigopoulos D.
First Department of Dermatology and Venereology, 'A. Sygros' Hospital, Athens, Greece.
Conventional therapies for human papillomavirus infection aim to remove clinically apparent lesions, while latent infection may remain, representing a threat for transmission and carcinogenesis. The use of a systemic agent may more effectively control the virus. We conducted a randomised placebo-controlled study to investigate the efficacy and safety of oral inociplex in the treatment of cervical condylomata acuminata (CA) that had been resistant to conventional therapies. Thirty-eight white European women, aged 20-43 years, with genital warts of the cervix, refractory to at least one conventional therapy, were randomly assigned to receive either inosiplex, 50 mg/kg daily peros for 12 weeks (group 1), or placebo (group 2). Of the 17 evaluable group 1 women, 4 responded to the treatment completely, 7 responded partially and 6 did not respond. Of the 19 group 2 women, none responded to the treatment completely, 3 responded partially and 16 did not respond. The therapeutic difference between women receiving active and placebo therapy was statistically significant (chi(2)= 6.69, P < 0.01) and remained significant when an intention-to-treat analysis was performed (chi(2)= 7.69, P < 0.01). None of the complete responders experienced recurrence during the 12-month follow up. Adverse effects were mild and resolved upon completion of therapy. Compared with placebo, inosiplex showed considerable efficacy with insignificant and reversible adverse effects and without recurrences. Inosiplex may represent an efficacious and safe alternative systemic form of therapy for cervical genital warts.

Pol Merkur Lekarski. 2005 Sep;19(111):379-82. Links
Immunological and clinical study on therapeutic efficacy of inosine pranobex.
Golebiowska-Wawrzyniak M, Markiewicz K, Kozar A, Derentowicz P, Czerwinska-Kartowicz I, Jastrzebska-Janas K, Waclawek J, Wawrzyniak ZM, Siwinska-Golebiowska H.
Zaklad Immunologii Klinicznej Instytutu Matki i Dziecka, Warszawie.
Many studies in vitro and in vivo have shown immunomodulating and antiviral activities of inosine pranobex. The object of this research was to examine the potential beneficial effects of inosine pranobex (Groprinosin) on immune system in children with cellular immunodeficiency as a prophylaxis of recurrent infections, mainly of viral origin. 50 mg/kg b.w/day of inosine pranobex in divided doses was given to the group of 30 children aged 3-15 years for 10 days in 3 following months. Clinical and immunological investigations were done before and after the treatment. Statistically significant rise of CD3T lymphocytes number (p = 0.02) and in this CD4T lymphocytes number (p = 0.02) as well as statistically significant improvement of their function (p = 0.005) evaluated with blastic transformation method were found. These laboratory findings were parallel to clinical benefits. Control study was performed in the group of children completed by randomization and treated in the same way with garlic (Alliofil).

Lik Sprava. 2004 Oct-Nov;(7):74-7.
[Efficiency of groprinosine in the complex treatment of acute virus hepatitis B]
[Article in Russian]
Karimov IZ.
35 patients with acute virus hepatitis of average severity were examined. They developed after short-term improvement of general state a negative dynamics of clinical and laboratory indexes. 21 patients have received traditional treatment, 14 patients additionally were prescribed groprinosine in a dose of 50 mg/kg daily per/os within 5-10 days. It was shown, that addition of gropfmosme to complex therapy positively influenced on the disease's course, promoted a rapid regress of clinical symptoms, normalization of biochemical indexes of liver's functions and decreased days of hospitalization.

No To Hattatsu. 2004 Jan;36(1):70-4.
Five patients with subacute sclerosing panencephalitis treated with intraventricular alpha-interferon and inosinpranobex
Oshiro S, Minema H, Shiroma N, Hirayasu K, Nakada Y.
Department of Pediatrics, Okinawa Seishi Ryogoen, Naha, Okinawa.
We followed up 5 patients with subacute sclerosing panencephalitis (SSPE) for 14 to 81 months. They were treated with alpha-interferon (INF-alpha) and oral inosinpranobex (INP) in an early stage of Jabbour stage II and within 5 months after the onset. On admission, Ommaya reservoir was implanted for the intrathecal administration of INF-alpha. The dose was 1 x 10(5) U/m2 initially and daily increased to 1 x 10(6) U/m2. A total dose of 30 x 10(6) U/m3 was given to them over a 4-weeks to 6-weeks period. After discharge, a dose of 15 x 10(6) U/m2 in three patients was given weekly and a dose of 30 x 10(6) U/m2 in the other patients. In addition, all patients received oral INP. One patient showed mild progression and remained in early stage of Jabbour stage II. In the remaining 4 patients, the disease progressed to Jabbour stage III. Despite the small number of patients studied here, the results suggest that treatment with INF-alpha plus oral INP is ineffective in an early stage of SSPE.

Pol J Vet Sci. 2004;7(2):97-102.
Effect of methisoprinol on virus replication in cell cultures.
Malaczewska J, Rotkiewicz Z.
Department of Infectious and Invasive Diseases, Chair of Clinical Microbiology and Immunology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn Oczapowskiego 13, 10-718 Olsztyn, Poland. stenia@uwm.edu.pl
The effect of Methisoprinol (active substance: isoprinozine) on the replication of two animal viruses, the TK900 strain of Aujeszky's disease virus and the Roakin strain of the Newcastle disease virus was investigated. When the maximal tolerable doses of the drug were added to two cell cultures (CECC and GMK), its effect on the level of infectious titres of theviruses and their adsorption were assayed. Investigations were also performed to assess the direct effect of Methisoprinol on the viral strains used. The final stage of the experiment aimed at analysing of the replication dynamics of the viruses in the presence of Methisoprinol. Methisoprinol showed no direct effect on the viruses used in the study. Nor did it affect their adsorption. The preparation applied to the culture 24 hours before infection did not influence the replication of viruses, but administered simultaneously with the infection significantly lowered the final titres of viruses. The highest inhibitory effect of the drug was observed during the analysis of the replication dynamics of both viruses in CECC and of pseudorabies virus in GMK cell culture upon the application of the maximal tolerable doses of Methisoprinol and low infectious doses of the viruses.

Vol. 284, Issue 1, G138-G144, January 2003
Inosine reduces inflammation and improves survival in a murine model of colitis
J. G. Mabley1, P. Pacher1, L. Liaudet2, F. G. Soriano2, G. Hasko2, A. Marton1, C. Szabo1,2, and A. L. Salzman1
1 Inotek Pharmaceuticals, Beverly, Massachusetts 01915; and 2 Department of Surgery, University of Medicine and Dentistry - New Jersey Medical School, Newark, New Jersey 01703
Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis.

J Child Neurol. 2003 Feb;18(2):104-8.
Combined treatment with subcutaneous interferon-alpha, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis.
Aydin OF, Senbil N, Kuyucu N, Gurer YK.
Department of Pediatric Neurology, Dr. Sami Ulus Children's Hospital, Ankara, Turkey.
We compared patients with subacute sclerosing panencephalitis who received treatment according to our protocol for at least 6 months (19 patients) with the patients who could not receive any treatment (13 patients). The treatment protocol consisted of oral isoprinosine (100 mg/kg/day), subcutaneous interferon alpha-2a (10 mU/m2/three times a week), and oral lamivudine (10 mg/kg/day). There were no statistical differences between the two groups according to Neurological Deficit Index, clinical stage, and average age on admission and also on the final evaluation after treatment. The mortality rates of both groups were similar: 3 (15.7%) for the treatment group and 6 (46%) for controls. The remission rates for the treatment and control groups were 7 of 19 (36.8%) and 0 of 13 (0%), respectively, and the difference was statistically significant (P = .036). The mean survival period of the treatment group was significantly longer than that of the control group (P = .01). In conclusion, this combination treatment protocol resulted in higher remission rates and longer survival periods when compared with controls, as well as a remission rate that was better than the spontaneous remission rate of 5%. For this reason, and as well as because interferon-alpha therapy has an easier route of application and a higher family compliance, we have considered this an alternative protocol for patients with subacute sclerosing panencephalitis.

Arch Neurol. 2003 Aug;60(8):1160-1.
Fulminating adult-onset subacute sclerosing panencephalitis in a 49-year-old man.
Gagnon A, Bouchard RW.
Department of Neurological Sciences, Centre Hospitalier Affilie Universitaire de Quebec-Hopital de l'Enfant-Jesus, Quebec, Quebec, Canada.
CONTEXT: Subacute sclerosing panencephalitis (SSPE) is a rare, slow viral infection caused by a defective measles virus. It is characterized by progressive mental deterioration associated with motor impairment and prominent myoclonus. In about 10% of all cases, the disease can progress rapidly and lead to death within a few months. The oldest previously reported fulminating case was in a 25-year-old man. OBJECTIVE: To emphasize the relationship between retinal involvement and acute SSPE by reporting the case of a 49-year-old man with clinical, laboratory, and pathological evidence of acute SSPE. SETTING: Hopital de l'Enfant-Jesus, Quebec, Quebec. REPORT OF A CASE: This man was referred to the Department of Neurological Sciences on March 21, 2001, because of recent behavioral changes and progressive cognitive impairment over the past few months. Medical history was unremarkable except for an episode of measles in his childhood. Neurological examination showed bilateral myoclonic jerks. Ophthalmic examination revealed bilateral macular swelling and papilledema. Electroencephalography showed periodic sharp and slow-wave discharges. Magnetic resonance imaging showed bilateral diffuse T2-signal hyperintensities in both periventricular and subcortical white matter. Cerebrospinal fluid antimeasles antibody titers were highly positive. An Omaya reservoir was inserted and therapy using a combination of high-dose intrathecal interferon alfa and oral isoprinosine were administered for 6 weeks. Despite transient subjective improvement in the patient's condition, it continued to deteriorate, he became bedridden, and he died on June 26, 2001. CONCLUSION: To our knowledge, this patient is the oldest case of SSPE reported in the literature. This patient and other patients with acute SSPE associated with bilateral macular swelling described in the literature raised the possibility of measles virus-acquired virulent neurotropism in the retina before invading the central nervous system.

Am. J. Respir. Crit. Care Med., Volume 164, Number 7, October 2001, 1213-1220
Inosine Reduces Systemic Inflammation and Improves Survival in Septic Shock Induced by Cecal Ligation and Puncture
LUCAS LIAUDET, JON G. MABLEY, FRANCISCO GARCIA SORIANO, PAL PACHER, ANITA MARTON, GYORGY HASKO, and CSABA SZABO
Inotek Corporation, Beverly, Massachusetts; and Department of Surgery, New Jersey Medical School, UMDNJ, Newark, New Jersey
Inosine is a naturally occurring purine formed from the breakdown of adenosine. Here we have evaluated the effects of inosine in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice subjected to CLP were treated with either inosine (100 mg/kg, intraperitoneally) or vehicle 1 h before and 6 h after CLP. After 12 h tumor necrosis factor , interleukin 6 (IL-6), and IL-10 were measured in plasma. Biochemical markers of organ damage, liver NAD+/NADH (indicator of the mitochondrial redox state), plasma nitrate, tissue myeloperoxidase (MPO, indicator of neutrophil accumulation) and malondialdehyde (MDA, indicator of lipid peroxidation), liver and lung chemokines (macrophage inflammatory protein 1 [MIP-1 ] and MIP-2), and ex vivo vascular reactivity in aortic rings were also measured. Mice treated with inosine had significantly lower levels of circulating cytokines. Organ damage was significantly reduced by inosine treatment, which was associated at the tissue level with an increased hepatic NAD+/NADH ratio, decreased MPO activity in the lung, reduced MDA formation in the gut and liver, and decreased MIP-1 and MIP-2 in the lung and liver. Furthermore, inosine significantly improved endothelium-dependent relaxant responses of aortic rings. These effects were associated with significant improvement of the survival of CLP mice treated with inosine, an effect that was still observed when inosine treatment was delayed 1 h after CLP, especially when it was associated with appropriate antibiotic treatment. Thus, inosine reduced systemic inflammation, organ damage, tissue dysoxia, and vascular dysfunction, resulting in improved survival in septic shock.