the term “ ngf ” means β - unit of human ngf . β - ngf has an amino acid sequence of 118 amino acids and is present as a dimer in solution . the amino acid and dna sequence is described in ullrich et al . ( 1993 ) ( 1 ). the pharmaceutical compositions which are used according to the invention and contain β - ngf may be administered in any sterile biocompatible pharmaceutical carrier , including , but not limited to , saline , buffered saline or dextrose solution , preferably in an acidic solution having a ph of about 4 to 5 , preferably in an acetate buffer . the amount of ngf protein which will be effective in the treatment of ms is in a dose between 0 . 05 μg and 5 μg / kg body weight at an interval of 1 to 21 days , preferably in 1 to 10 injections . it is further preferred to use 3 . 5 to 350 μg / injection . methods of introduction include , but are not limited to , intradermal , intramuscular , intraperitoneal , intravenous , subcutaneous , oral , intrapeulmonal and intranasal administration . in addition , it may be desirable to introduce the pharmaceutical composition of the invention into the central nervous system by any suitable route , including intrathecal , e . g . intraventricular injection . intraventricular injection may be facilitated by an intraventricular catheter , for example attached to a reservoir , such as an implantable port catheter system , such as the periplant ® filtrosafe ( b . braun gmbh , spangenberg , de ). furthermore , it may be desirable to administer the pharmaceutical compositions , which are used according to the invention , locally to the area in need of treatment . this may be achieved by , for example , and not by way of limitation , injection by means of a catheter or by means of an implant , said implant being of a porous , non - porous or gelatinous material , including membranes , such as sialastic membranes or fibers . ngf is preferably administered during the relapse period . if high doses are used , only a few or even one bolus application is sufficient . the following examples and fig1 are provided to aid the understanding of the present invention , the true scope of which is set forth in the appended claims . it is understood that modifications can be made in the procedures set forth without departing from the spirit of the invention . fig1 shows coronal magnetic resonance tomography imaging ( mri ) of pig brains 7 days after lysolecithin - induced demyelination . a ) lesioned animal , receiving sham - treatment with a single intraventricular injection of 70 μg cytochrom c . arrows point to hyperintensity in the subcortical white matter of the lesioned side ( r — right hemisphere ) as compared to the non - lesioned left hemisphere ( l ). b ) identically lesioned animal as shown in a ), receiving a single intraventricular injection of 70 μg ngf . note that both hemispheres are symmetrically configurated with no remaining hyperintensity in the lesioned side ( r ). an experimental model of demyelination was established in the female , adult “ göttingen mini pig ” ( age : 10 - 14 months , weight : 25 - 30 kg ) by stereotaxic injection of lysolecithin ( ll ) at multiple sites into the periventricular subcortical white matter of the brain ( usually 2 - 3 injection sites located in one hemisphere ; 5 to 25 μl of 1 % ll in 0 . 9 % saline per lesion infused over a period of 15 min ). this infusion causes a rapid reduction of myelin sheaths within the diffusion area of the detergent ( blakemore ( 1978 ) ( 7 )). immediately after ll application , a catheter system ( periplant filtrosafe ®, braun , melsungen , germany ) is implanted either into the lateral ventricle of the brain or in the subarachnoidal space of the lumbar spinal cord ( motsch and robert ( 1987 ) ( 8 ); krames and lanning ( 1993 ) ( 9 )). two ways of ngf application were used : 1 ) after fixation of the catheter with ionocem ® bone cement ( ionos , seefeld , germany ) the intrathecal catheter is connected with a subcutaneous drug delivery system ( periplant filtrosafe ®, braun , melsungen , germany ) which is implanted subcutaneously in the upper back region . ngf ( dissolved in phosphate - buffered saline , ph 7 . 2 ) injected every 2nd day through the skin into the port , starting 1 day after initial ll lesions , by single bolus injections into the port at a dose of 0 . 05 - 3 μg / kg body weight ( 1 . 25 to 90 μg per injection , corresponds to 3 . 5 to 210 μg per injection ( human weight : 70 kg ). 1 - 5 injections were carried out into the cerebrospinal fluid within a period of 1 - 12 days after ll - induced demyelination . 2 ) the effect of single bolus injections of ngf described above was compared with the continuous infusion of ngf into the lateral ventricle via osmotic minipumps ( alzet ® for 1 - 12 days at a dose of 0 . 5 μg / h ). controls were carried out by replacement of ngf solution with an equal dose of cytochrome c applied in the same ways and time interval as described in 1 ) and 2 ). at the end of the ngf ( control , respectively ) application period , the experimental animals were sacrificed , the brain was removed and prepared for histological examination : the areas of interest were studied with routine histological ( h . e . staining , luxol fast blue staining ), immunocytochemical ( myelin basic protein — mbp ) and electronmicroscopic ( oligodendrocytes , myelin lamellae ) procedures . injection of ll causes a widespread demyelination throughout the area of diffusion . chronic infusion of infusion of ngf via alzet pumps : an improved and accelerated remyelination of the lesioned myelin sheaths of nerve fibers was detected within the application interval as compared to controls . significant regeneration was observed 7 days after initial lesion whereas severe demyelination was still present in the white matter of sham - treated animals . bolus ngf injection every 2nd day : significant regeneration was also noted under ngf treatment in this system , with no apparent differences to animals receiving chronic infusions of ngf . furthermore , ngf injected in the csf space in the area of the spinal cord showed the same positive effect on remyelination as found for intraventricular injections . the data demonstrate that injections of ngf into the cerebrospinal fluid lead to an improved and accelerated remyelination , most likely due to regeneration and proliferation of oligodendrocytes . compared to chronic ngf infusion with the help of pumps , the application via an intrathecally implanted port allows an easy - to - handle , save and inexpensive way of supplying the brain with the neurotrophin at an adjustable and optimal concentration for maximal therapeutic efficacy . in addition , in patients with multiple sclerosis suffering from repeated attacks ( i . e . relapsing - remitting ms ) immediate interval treatments at the time of the attack within a period of several years are possible , minimizing the risk of complications ( i . e . infections ) due to necessary changes of catheter systems or refills of pumps needed during chronic or repeated infusions . there is a clear correlation between the degree of remyelination and functional improvements in the state of demyelinating diseases ( ifnβ study group ( 1993 ) ( 10 )). data obtained from animal models using pigs have a great clinical relevance in biomedical research , i . e . numerous studies on the cardiovascular system , skin and peripheral nervous system that have proven that data from porcine tissue are applicable on human subjects . ( 9 ) krames , e . s ., lanning , r . m ., j . pain symptom manage . 8 ( 1993 ) 539 - 548 ( 10 ) the ifnβ multiple sclerosis study group , neurology 43 ( 1993 ) 662 - 667 ( 12 ) olson , l ., et al ., j . neural . transm . [ p - d sect ] 4 ( 1992 ) 79 - 95
a method is presented for regenerating oligodendrocytes in diseases such as multiple sclerosis by administering human β nerve growth factor by bolus injection . treatment comprises 1 - 10 bolus injections in a dose of 0 . 05 to 5 . 0 μg / kg body at an interval of 1 to 21 days .