Insulin-like growth factors and somatomedin B in the cerebrospinal fluid of patients with dementia of the Alzheimer type

Cerebrospinal fluid levels of radioreceptor assayable insulin-like growth factors (RRA-IGFs) and immunoreactive somatomedin B (SMB) (RIA-B) were determined in apparently healthy individuals and in patients with dementia of the Alzheimer type (AD). The CSF levels of RIA-B and RRA-IGFs did not alter from the healthy controls. After being acidified, the CSF from the controls and from the presenile ADs were separated over a G-50 fine Sephadex . The RRA-IGFs activity eluted in three peaks. The results indicate that the major constituent of CSF RRA in both AD patients and controls is an IGF binding protein. The two minor peaks eluted at approximately 9 K and 6 K, corresponding to the elution positions of "big" IGF-2 and IGF-2.     

癫痫患者神经元特异性烯醇化酶和胰岛素样 生长因子1的变化及临床意义

目的观察癫痫发作3 d内患者血清神经元特异性烯醇化酶(NSE)和胰岛素样生长因子1(IGF-1)浓度的变化及其临床意义。方法选取63例特发性癫痫患者作为病例组,以37例年龄及性别相匹配的体检健康者作对照组。采用ECLIA、ELISA测定血清NSE和IGF-1的浓度。结果病例组血清NSE和IGF-1浓度与对照组比较明显升高,差异有统计学意义(P<0.05)。血清NSE和IGF-1ROC曲线下面积分别为0.767和0.663。癫痫患者血清NSE和IGF-1浓度之间存在相关性(r=0.379,P<0.01)。结论血清NSE、IGF-1浓度在痫性发作后3 d内升高,提示其可作为判断痫性发作后早期脑损伤及机体早期启动神经保护的生化指标,具一定临床应用价值。癫痫患者血清NSE和IGF-1浓度之间存在相关性,提示它们可能共同参与了癫痫的发病过程。     

Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism

There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.     

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

Using radioimmunoassay we measured serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in patients with relapsing multiple sclerosis (MS) and a benign course (Expanded Disability Status Scale (EDSS) < or =3 despite > 10 years disease duration), relapsing MS with cumulative disability leading to an EDSS score >4 within 10 years of disease duration, primary progressive MS and healthy controls. We found no differences in IGF-1 and IGFBP-3 serum levels, and the IGF-1/IGFBP-3 ratio between the four groups. However, there was a significant correlation (P =0.005) between IGFBP-3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS.     

Rat astroglial somatomedin/insulin-like growth factor binding proteins: characterization and evidence of biologic function

Specific binding proteins (BPs) to somatomedin/insulin-like growth factors (Sm/IGFs) have been identified in conditioned media from a variety of cells in culture. By affinity cross-linking using disuccinimidyl suberate, we have covalently cross-linked radiolabeled somatomedin-C/insulin-like growth factor I (Sm-C/IGF I), insulin-like growth factor II (IGF II) and insulin to BPs in conditioned medium (CM) from cultured astroglial cells derived from cerebral cortices of neonatal rats. Two species of radiolabeled Sm/IGF BP complexes of 40,000 Da (40K) and 45K were identified. Competition with unlabeled Sm-C/IGF I and IGF II demonstrated that the BPs in each complex have similar affinities for Sm-C/IGF I and IGF II. The BP in the 45K complex was about 5-fold more sensitive to competition with unlabeled Sm/IGFs than the BP in the 40K complex, suggesting that it either has a higher affinity for Sm/IGFs or is less abundant. Evidence that the BPs in each complex are distinct includes the following findings: (1) insulin competed with Sm/IGF for binding to the 45K complex, but not the 40K complex, and (2) the BP in the 40K complex, but not the 45K complex, was recognized by antibodies raised against a BP purified from CM of buffalo rat liver (BRL) 3A cells. Growth hormone did not affect the apparent secretion of either BP. The binding activity of both BPs was retained after mild heat treatment, changes to extremes of pH (2-10), and prolonged storage at -20 degrees C, but was destroyed after heating to higher temperatures (80 degrees C and greater), reduction, and proteolytic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men

Circulating levels of growth hormone (GH) change during the process of aging. Decline of cognitive functioning with aging is also well established. In this study, we investigated whether insulin-like growth factor 1 (IGF-1) and the GH response to a challenge of GH-releasing hormone and GH-releasing peptide 6 were associated with age-sensitive cognitive functions, but not with functions that do not decline with aging, in 17 healthy male subjects aged between 66 and 76 years. In addition, relations with anthropometric measures were examined. Neuropsychological performance was scored on tests of variables not sensitive to aging (general knowledge, vocabulary, basic visual perception and reading ability), and of variables sensitive to aging (visuoconstructive ability, perceptual motor and mental processing speed, and verbal long-term memory). After correcting for education, the serum GH response was significantly associated with two age-sensitive cognitive tests (measures of mental processing speed), but with none of the tests not sensitive to aging. However, the direction of the association was opposite to the relation between IGF-1 and these cognitive tests: higher levels of GH response were associated with poorer cognitive performance, whereas higher levels of IGF-1 were associated with better performance. GH response, but not IGF-1, was inversely correlated with body mass index. The results are in accordance with previous research suggesting a disruption of the relation between IGF-1 and GH secretion in older age.     

Characterization of somatomedin/insulin-like growth factor receptors and correlation with biologic action in cultured neonatal rat astroglial cells

The role of somatomedin/insulin-like growth factors (Sm/IGFs) in neural growth and development is not clearly defined. To characterize Sm/IGF receptors and to correlate binding with the biologic actions of Sm/IGFs in a homogeneous population of neural cells, we isolated and studied a nearly pure population of cultured astroglial monolayers derived from cerebral cortices of neonatal rats. Binding of radiolabeled Sm/IGFs was specific, saturable, and reversible, with 90% of the binding occurring within 6 hr of incubation at 4 degrees C. Competitive binding studies with Sm-C/IGF I yielded curvilinear Scatchard plots, while studies with IGF II and multiplication stimulating activity (MSA) yielded linear plots, suggesting that 125I-Sm-C/IGF I binds to more than 1 receptor species, and 125I-IGF II and 125I-MSA bind to one only. These findings were supported by affinity-labeling studies with radiolabeled Sm/IGFs using disuccinimidyl suberate as a cross-linking agent. Sm-C/IGF I appeared to bind to both type I and II Sm/IGF receptors, because cross-linked 125I-Sm-C/IGF I-receptor complexes with molecular weight (Mr) of greater than 300,000 (300K) and 130K (type I receptor) were observed under nonreducing and reducing conditions, respectively, as were 220 and 260K complexes (type II receptor) under the same respective conditions. 125I-IGF II and 125I-MSA, however, bound only to the Mr 220 and 260K moieties under nonreducing and reducing conditions, respectively, suggesting that these peptides bind only to the type II receptor. Competitive binding studies of the cross-linked moieties were consistent with this interpretation. In contrast, 125I-insulin bound poorly to astroglia (less than 0.5% specific binding), and cross-linking studies could not definitely distinguish among low-affinity binding to the type I Sm/IGF receptor, binding to a paucity of insulin receptors, or both. In addition, by combining autoradiography to localize 125I-Sm/IGFs binding on astroglial cells and immunocytochemistry with anti-glial fibrillary acidic protein to identify the cell type, we have demonstrated cell-surface binding and apparent internalization of radiolabeled Sm/IGFs. Concurrent studies of Sm/IGF stimulation of 3H-thymidine incorporation revealed that these cells were most sensitive to Sm-C/IGF I, followed by IGF II and MSA, and insulin. MSA and IGF II, however, were the most potent followed by Sm-C/IGF I and then insulin. Half-maximal stimulations of 3H-thymidine incorporation corresponded closely with half-maximal binding displacement for Sm-C/IGF I and less so for IGF II and MSA.(ABSTRACT TRUNCATED AT 400 WORDS)     

Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects

Anaemia is a risk factor for cardiovascular morbidity and mortality. Among factors responsible for anaemia, insulin-like growth factor-1 (IGF-1) is a plausible candidate. We evaluated the association of IGF-1 with haemoglobin (Hb) concentration and anaemia in a cohort of 1,039 Caucasians subjects. Subjects with anaemia exhibited lower IGF-1 (p=0.006), and higher hsCRP levels (p=0.003). To estimate the independent contribution of variables to Hb concentration, a multivariable regression analysis was modeled including age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, fasting insulin, IGF-1, fibrinogen, hsCRP, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), serum iron, estimated glomerular filtration rate (eGFR), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The variables significantly associated with Hb concentration were gender (p<0.0001), IGF-1 (p<0.0001), waist circumference (p=0.02), hsCRP (p<0.04), MCH (p<0.0001), MCV (p<0.0001), serum iron (p=0.001), IGF-1 (p=0.003), hsCRP (p=0.008), and waist circumference (p=0.01), accounting for 54.0% of its variation. Hb concentration was significant lower in subjects in the lowest IGF-1 quartile as compared with those in the third (p=0.02) and fourth (p=0.001). In a logistic regression model adjusted for age, gender, BMI, waist circumference, blood pressure, fasting glucose, fasting insulin, fibrinogen, hsCRP, MCH, MCV, serum iron, eGFR, and treatment with ACE inhibitors or ARBs, subjects in the first quartile of IGF-1 had a 2.49-fold higher risk of having anaemia as compared with those in the fourth (odds ratio 2.70, 95% confidence interval 1.02-7.16). Our data suggest that low IGF-1 may be an important contributor to mild anaemia.     

RNA interference affects tumorigenicity and expression of insulin-like growth factor-1, insulin-like growth factor-1 receptor, and basic fibroblast growth factor-2 in rat C6 glioma cells

BACKGROUND： Human gliomas are more likely to express basic fibroblast growth factor-2 （FGF-2） insulin-like growth factor-1（IGF-1）, and IGF-1 receptor （IGF-1R） than normal brain tissue. These factors activate signal transduction systems of Ras/MAPK and PI3K/Akl, which promote glioma growth. OBJECTIVE： To utilize RNA interference （RNAi） technique to down-regulate FGF-2, IGF-1, and IGF-1R gene expression, and to investigate the effects of these genes on rat C6 glioma cells, as well as the feasibility of RNAi for treating glioma. DESIGN, TIME AND SETTING： This neurooncological, randomized, controlled, in vivo and in vitro experiment, which used RNAi methodology, was performed at the Laboratory of Molecular Biology, Institute of Biochemistry, Chinese Academy of Sciences between August 2005 and February 2008. MATERIALS： Rat C6 cell lines were purchased from Shanghai Institute of Cellular Biology Affiliated to Chinese Academy of Sciences. Small interfering RNA （siRNA） was synthesized by Shanghai GenePharma. Anti-IGF-1, anti-IGF-1R, anti-FGF-2, anti-mouse and anti-rabbit IgG G1-HRP antibodies were provided by Santa Cruz Biotechnology, USA. Four to six week-old BALB/c nude mice were purchased from the Laboratory Animal Center, Chinese Academy of Sciences. METHODS： C6 glioma cells were transfected with siRNA, which was chemically synthesized in vitro to correspond to endogenous FGF-2, IGF-1, and IGF-1R genes. The inhibition ratio of targeting mRNA expression was detected by semiquantitative RT-PCR, and protein expression was determined by Western blot analysis. C6 glioma cell proliferation was observed using a growth curve C6 glioma cell apoptosis rate and cell cycle were detected by flow cytometry. C6 glioma cell growth regression was observed by transwell migration assay. In addition, nude mouse subcutaneous tumor models were used in this study. For studying the anti-tumor effects of IGF-1 and IGF-1R siRNA, two blank control groups, with six mice each, were set up： A （2.5 μg siRNA was injected one week after C6 cells were inoculated, Le., when tumor volume reached 8 mm × 8 mm） and B （siRNA was injected at the same time with C6 cells were inoculated. To study the effects of FGF-2 siRNA, the groups consisted of a blank control group, negative control group, 2.6 μg siRNA group, 4 μg siRNA group, and 5.3 μg siRNA group, with six mice each. MAIN OUTCOME MEASURES： mRNA and protein inhibition ratio of FGF-2, IGF-1, and IGF-1 R; C6 glioma cell proliferation, apoptosis, and cycle growth arrest; C6 glioma cell growth regression and subcutaneous tumorigenicity rates. RESULTS： All siRNA constructs proved to be effective. After 48 hours, transfection of 200 nmol/L siRNA resulted in a FGF-2 or IGF-1R gene inhibition ratio 〉 80% and an IGF-1 gene inhibition ratio of approximately 70%. Protein expression levels for FGF-2, IGF-1, and IGF-1R decreased in a dose-dependent manner following siRNA transfection, with an inhibition rate 〉 85%, 60%, and 50%, respectively. C6 glioma cell proliferation and apoptosis rates increased in proportion to siRNA. The apoptosis rate of C6 glioma cells induced by FGF-2, IGF-1, and IGF-1R siRNA was 39.96%, 15.07% and 22.47%, respectively （P 〈 0.01）. Transfection of 200 nmol/L IGF or IGF-1R siRNA for 48 hours suppressed C6 glioma cell migration. At 30 days after intratumoral injection of 2.6, 4, and 5.3 tJg FGF-2 siRNA, tumor growth regression rate of FGF-2 siRNA was 56%, 67%, and 86%, respectively. The tumor growth regression rate was 71.88% and 45.71%, respectively, when IGF-1 or IGF-1R siRNA was intratumorally injected 1 week after C6 glioma cell transplantation. When IGF-1 or IGF-1 R siRNA was intratumorally injected during C6 glioma cell transplantation, the tumor growth regression rate was 78.13% and 74.29%, respectively. CONCLUSION： siRNA transfection downregulated gene expression of FGF-2, IGF-1, and IGF-1R In addition, siRNA treatment markedly suppressed glioma cell proliferation, growth, and migration, and concomitantly reduced subcutaneous tumorigenicity.     

Serum insulin-like growth factor-I levels in amyotrophic lateral sclerosis.

The serum concentrations of the myotrophic hormone insulin-like growth factor-I (IGF-I) in 23 patients with amyotrophic lateral sclerosis were not significantly different from those found in the sera of 13 control patients. There was no difference in binding of 125I-IGF-I by serum from patients with amyotrophic lateral sclerosis in comparison with that found in the controls. These results indicate that immunoreactive IGF-I concentrations are normal in patients with amyotrophic lateral sclerosis and that such patients do not have significant antibodies binding their endogenous IGF-I.     

Salivary and serum insulin-like growth factor (IGF-1) assays in anorexic patients

Objectives. The purpose of this study was to measure the salivary and serum free IGF-1 concentration of patients with anorexia nervosa (AN) in comparison to an average population. Methods. A controlled clinical trial was designed for an age- and gender-matched group of 121 AN patients and 77 healthy individuals. A clinical examination was made and blood and salivary samples were taken during the acute stage of AN (BMI < 15 kg/m²) in the first week of hospitalization. An enzyme immunoassay (ELISA) suitable for measuring free IGF-1 was used. Results. Anorexic patients had significant reductions in salivary unstimulated flow rate (UFR), pH and free IGF-1 levels in their saliva and serum. Significant correlations between serum IGF-1 and BMI; salivary IGF-1 and UFR and pH were detected. Conclusions. Salivary and serum IGF-1 analyses appear to be a reliable biochemical indicator of malnutrition in AN patients. Measurement of salivary IGF-1 levels would allow new perspectives in monitoring AN in its early stages.     

Immunoreactive somatomedin B is increased in serum in patients with major depressive disorder

Serum levels of immunoreactive somatomedin B (RIA-B) were investigated in patients with major depressive disorder both in the acute state and during remission at 8 h and 22 h and at 22 h after the dexamethasone suppression test. Elevated levels of RIA-B at 8 h and at 22 h after the dexamethasone suppression test were found consistently in the patient group compared with the healthy controls. No indication was obtained that the patients' clinical condition or depressive symptomatology as revealed by their CPRS score, psychotropic medication or TSH, prolactin, melatonin or cortisol levels was significantly related to the RIA-B levels.     

Growth hormone and somatomedin serum levels in patients with major depressive illness undergoing electroconvulsive therapy

Thirty-three patients with major depressive illness received electroconvulsive therapy (ECT), and serum growth hormone (GH) levels were measured 30, min before and 1, 5, 15, 30 and 60 min after treatment. Six of the patients were studied 2 days before the first ECT (ECT-1) while receiving anaesthesia only. The anaesthesia given appeared to depress GH levels, which were significantly lower at 1 and 5 min after ECT than before treatment. When ECT was given there was a recovery of the GH level at 60 min, indicating a stimulatory effect of ECT on GH secretion. In 26 of the patients also investigated during the sixth and last ECT (ECT-6) in a series, no such recovery was observed. This may be due to changes in the sensitivity of intracerebral monoaminergic receptors in neurons controlling GH secretion from the pituitary gland. Since inhibition of GH secretion is mediated via beta-adrenergic pathways, the depression of GH secretion may be due to ECT-induced supersensitivity of postsynaptic beta-adrenergic receptors. In 27 of the patients serum somatomedin A, measured by radioreceptorassay (SMA-RRA), was analysed before ECT-1 and in 19 patients before ECT-6. In seven subjects the SMA-RRA was measured 30 min before and 1, 5, 15, 30, and 60 min after ECT-1. SMA-RRA levels were mainly within the normal range for age and did not change during ECT. No difference in SMA-RRA levels was observed before ECT-1 and ECT-6. This indicates that, although abnormalities in the GH-response to challenge stimuli have been reported in adults with major depressive disorder, their GH production is normal.     

High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors

CONTEXT: Predisposition to alcoholism is likely an interaction between genetic and environmental factors that confer vulnerability and protection. Alcoholic subjects have low levels of dopamine D(2) receptors in striatum, and increasing D(2) receptor levels in laboratory animals reduces alcohol consumption. OBJECTIVES: To test whether high levels of D(2) receptors may be protective against alcoholism and whether this is mediated by their modulation of activity in orbitofrontal cortex and cingulate gyrus (regions involved in salience attribution, emotional reactivity, and inhibitory control). DESIGN: Research (nonalcoholic subjects with a family history of alcoholism) and comparison (nonalcoholic subjects with a negative family history) sample. SETTING: Outpatient setting. PARTICIPANTS: Fifteen nonalcoholic subjects who had an alcoholic father and at least 2 other first- or second-degree relatives who were alcoholics (family-positive group) and 16 nonalcoholic controls with no family history of alcoholism (family-negative group). MAIN OUTCOME MEASURES: Results of positron emission tomography with raclopride C 11 to assess D(2) receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function). Personality measures were obtained with the Multidimensional Personality Questionnaire. RESULTS: Availability of D(2) receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D(2) receptors were associated with metabolism in anterior cingulate (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal (Brodmann area 9/10) cortices, and with personality scores of positive emotionality. CONCLUSIONS: The higher-than-normal D(2) receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D(2) receptors may protect against alcoholism. The significant associations between D(2) receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D(2) receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions.     

小鼠成骨细胞Wnt信号通路相关因子表达与胰岛素样生长因子1的影响

背景：胰岛素样生长因子1可促进细胞增殖、分化,但其具体作用机制尚不清楚。 目的：观察胰岛素样生长因子1对小鼠成骨细胞增殖﹑分化的影响,及Wnt信号通路相关因子mRNA的表达。 方法：向体外培养的小鼠成骨细胞中加入25 μg/L的胰岛素样生长因子1,分别于培养的第1,2,3,4,5天用CCK-8比色法检测细胞增殖率;于培养的第3,6,9天应用酶联免疫法检测细胞内碱性磷酸酶活性;细胞培养第3天提取总RNA,采用Real-time RT-PCR检测Wnt-3a,低密度脂蛋白受体相关蛋白5,β-catenin mRNA的表达。 结果与结论：25 μg/L胰岛素样生长因子1能够促进成骨细胞增殖,提高碱性磷酸酶活性,而且明显增加成骨细胞中Wnt-3a、低密度脂蛋白受体相关蛋白5、β-catenin mRNA的表达(P < 0.05)。说明胰岛素样生长因子1能够促进成骨细胞的增殖和分化,Wnt信号通路参与了该调控过程。     

Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type

Summary After acid gelchromatography cerebrospinal fluid and serum levels of immunoreactive insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) were determined in patients with dementia of the Alzheimer type (AD) and in healthy subjects. The AD CSF levels of immunoreactive IGF-1 did not differ from the subjects but the levels of immunoreactive IGF-2 was significantly elevated in both serum and CSF in the AD patient group. Additionally immunoreactive IGF-1 in AD serum was found to be significantly elevated. To characterize the CSF IGF binding protein activity (IGFBP), ligand blotting was performed on whole CSF from AD patients and subjects. The results demonstrate two major forms of IGFBP in CSF with approximate molecular weights of 33 KDa and 30 KDa. The two IGFBP forms are suggested to represent IGFBP-2 and IGFBP-6. A highly significant increase in both the IGFBPs was observed in the CSF of the AD patients compared to the healthy subjects.     

Circulating leptin levels and weight loss in Alzheimer's disease patients

Weight loss is common in Alzheimer's disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer's (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.     

A pilot study of recombinant insulin-like growth factor-1 in seven multiple sderosis patients

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-1 (rhIGF-1) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sderosis (MS) patients. Monthly clinical and MPI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-1. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included dinical and MRI measures of disease activity including: white matter lesion load (WMLL), magnetization transfer ratio (MTR), T1-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-1 (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-1 was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-1 did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-1 alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination.