cns drug reviews

CNS DRUG REVIEWS
Volume 10, Number 2, Summer2004
Israel Hanin and Alexander Scriabine
Editors
NEVA PRESS, INC.

200 SELECTED ABSTRACTS FROM AD/PD 2003
E-SAR-94010 (LipoEsar®):
A Pleiotropic Lipoprotein Compound
with Powerful Anti-atheromatous
and Lipid Lowering Effects
Ramón Cacabelos, Ana Isabel Vallejo, Valter Lombardi,
Lucía Fernández-Novoa, Víctor Pichel
EuroEspes Biomedical Research Center & Ebiotec, Bergondo, Coruña, Spain
E-SAR-94010 (LipoEsar) is a natural product extracted from the marine species S. pilchardus,
by means of non-denaturing biotechnological procedures. The main chemical
ingredient of LipoEsar is a lipoprotein (60-80%) whose micelle structure probably mimies
that of physiological lipoproteins involved in lipid metaboiism. In preclinical studies
LipoEsar has shown to be effective in (a) reducing blood cholesterol (Cho), triglyceride
(TG), uric acid (UA), and glucose (Glu) levels, as well as liver alanine aminotransferase
(ALT), and aspartate aminotransferase (AST) activity; (b) enhancing immunological
function by regulating both lymphocyte and microglia activity; (c) inducing antioxidant
effects mediated by superoxide dismutase activity; and (d) improving cognitive function.
Clínical studies have revealed that LipoEsar reduces blood total cholesterol (T-Cho)
(20-30%), Glu (5-10%), UA (10-15%), TG (30-50%), ALT and AST, after 1-3 months
of treatment at a daily dose of 250-500 mg (t.i.d.) The effect on T-Cho is the result of decreasing
LDL-Cho levels and increasing HDL-Cho levels in parallel with an improvement
in hepatic protection reflected by reduction in ALT, AST, and GGT activity. Most of these
therapeutic effects on the regulation of lipid metabolism tend to show an age-dependent
pattem and are also associated with specific genomic profiles in the population. In addition,
LipoEsar diminishes the size of xanthelasma plaques by 30-60% after 6-9 months
of treatment. Similar effects can be observed on atheromatous plaques on the aortic wall
of patients with familial and sporadic hypercholesterolemia.
LipoEsar is the first marine biotechnological product with lipoprotein structure displaying
hypolipemic activity in blood and tissues acting as a potential neuroprotectant in
cerebrovascular disorders and arteriosclerosis.
Preliminary studies indícate that the biological activity of LipoEsar is genotype-dependent.
Since genetic defeets in the APOE gene result in famiíial dysbetalipoproteinemia
or type III hyperlipoproteinemia (HLP-III) with increased plasma Cho and TG as a consequence
of impaired clearance of chylomicron and VLDL remnants, in the present paper
we have investigated the influence of different APOE genotypes on the therapeutic response
of LipoEsar in patients with chronic dyslipemia. The study has been performed in
419 patients (age: 55.24 ±17.71 years; range: 9-96 years) of both sexes (females:
N = 212; age: 57.04 ± 17.68 years; range: 15-96 years; males: N- 207; age: 53.38 ± 17.58
CNS Drug Reviews, Vol. 10, No. 2, 2004

SELECTED ABSTRACTS FROM AD/PD 2003 201
years; range: 9-91 years). The distribution of the APOE genotypes and mean age of the
different APOE clusters were the following: (1) APOE-2/2 = 1.15% (57.25 db 20.61
years); (2) APOE-2/3 = 7.18% (55.40 ± 15.43 years); (3) APOE-2/4 = 1.73% (52.83 ±
20.56 years); (4) APOE-3/3 = 66.38% (57.35 ±16.79 years); (5) APOE-3/4 = 21.55%
(59.33 ±18.19 years); and (6) APOE-4/4 = 2.01% (58.85 ± 18.65 years). The frequency
of the APOE genotypes in patients with dyslipemia is very similar to that of the general
Spanish population as previously reported by our group. No significant differences were
found in age among the different APOE genotypes of randomly selected patients. The biological
parameters evaluated in the study include the following: Glu, T-Cho, HDL-Cho,
LDL-Cho, TG, Urea, UA, proteins, calcium, ALT, AST, GGT, Na, K, Cl, RCB, HTO, Hb,
VCM, HCM, CHC, RDW, lymphocytes, monocytes, granulocytes, and platelets. After one
month of treatment, LipoEsar (750 mg/day, p.o.) reduced the serum levéis of Glu
(p < 0.006), T-Cho (p < 0.0001), LDL-Cho (p < 0.0001), TG (p < 0.0001), urea (p < 0.03),
UA (p

E-SAR-94010 (LipoEsar®): Compuesto lipoproteico pleiotrópico con actividad
hipolipemiante y anti-ateromatosa
Ana Isabel Vallejo, Valter Lombardi, Lucía Fernández-Novoa, Victor Pichel, Luis Amado,
Ramón Cacabelos
EBIOTEC y Centro de Investigación Biomédica EuroEspes, 15166-Bergondo, Coruña
El E-SAR-94010 (LipoEsar®) es un compuesto lipoproteico pleiotrópico extraido por
procedimiento biotecnológicos no desnaturalizantes de la especie marina S. pilchardus. El
principal componente estructural de la composición química de LipoEsar son lipoproteínas
(60-80%) de potencial estructura micelar que compiten con estructuras químicas del tipo
LDL-cholesterol, confiriendo a este compuesto natural un poderoso efecto regulador del
metabolismo lipídico y de la formación de placas de ateroma.
En estudios preclínicos el LipoEsar ha demostrado un claro efecto hipolipemiante,
disminuyendo los niveles de triglicéridos, colesterol total, LDL-colesterol, urea, ácido úrico
y transaminasas hepáticas, al tiempo que incrementaba los niveles de HDL-colesterol.
Otros efectos de LipoEsar incluyen: (a) potenciación inmunológica, (b) regulación de la
actividad microglial en cerebro, (c) actividad antioxidante mediada por superóxido
dismutasa, y (d) acción procognitiva.
En estudios clínicos en pacientes con hiperlipemia crónica (N=204), LipoEsar (750-1500
mg/día, p.o. x 3 meses) ha disminuido los niveles de colesterol total (20-30%), glucosa (5-
10%), ácido úrico (10-15%), triglicéridos (30-50%), GOT (10-30%) y GPT (5-15%), con
aumento paralelo de HDL-colesterol (10-20%)..
LipoEsar reduce las placas de xantelasma periorbitario en un 30-60% tras 3 meses de
tratamiento a dosis convencionales y en pacientes con placas de ateroma en aorta
abdominal disminuye el tamaño de la placa aterogénica en un 10-30% medida digitalmente
por tomografía axial computerizada.
En estudios clínicos paralelos LipoEsar ha demostrado potenciar el efecto hipolipemiante
de la mayoría de las estatinas, protegiendo al hígado frente a la acción hepatotóxica de
algunas de estas sustancias en pacientes susceptibles.
LipoEsar es la primera lipoproteína pleiotrópica de origen marino con actividad fisiológica
reguladora del metabolismo lipídico en animales y humanos.